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Review

A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones

by
Joonseong Hur
1,
Jaebong Jang
2,* and
Jaehoon Sim
3,*
1
Natural Products Research Institute, Korea Institute of Science and Technology (KIST), 679 Saimdang-ro, Gangneung 25451, Korea
2
College of Pharmacy, Korea University, Sejong 30019, Korea
3
College of Pharmacy, Chungnam National University, Daejeon 34134, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(5), 2769; https://doi.org/10.3390/ijms22052769
Submission received: 25 January 2021 / Revised: 26 February 2021 / Accepted: 3 March 2021 / Published: 9 March 2021
(This article belongs to the Special Issue Natural and Synthetic Lactones: Isolation, Synthesis, Biotransformations and Biological Activity)
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Abstract

:
γ-Butyrolactone, a five-membered lactone moiety, is one of the privileged structures of diverse natural products and biologically active small molecules. Because of their broad spectrum of biological and pharmacological activities, synthetic methods for γ-butyrolactones have received significant attention from synthetic and medicinal chemists for decades. Recently, new developments and improvements in traditional methods have been reported by considering synthetic efficiency, feasibility, and green chemistry. In this review, the pharmacological activities of natural and synthetic γ-butyrolactones are described, including their structures and bioassay methods. Mainly, we summarize recent advances, occurring during the past decade, in the construction of γ-butyrolactone classified based on the bond formation in γ-butyrolactone between (i) C5-O1 bond, (ii) C4-C5 and C2-O1 bonds, (iii) C3-C4 and C2-O1 bonds, (iv) C3-C4 and C5-O1 bonds, (v) C2-C3 and C2-O1 bonds, (vi) C3-C4 bond, and (vii) C2-O1 bond. In addition, the application to the total synthesis of natural products bearing γ-butyrolactone scaffolds is described.

1. Introduction

γ-Butyrolactone, a five-membered heterocycle containing ester functionality, has been broadly studied in the drug discovery field since it is one of the privileged structures of biologically active small molecules. Several γ-butyrolactone-containing drugs have been FDA-approved and used in clinic for diverse purposes such as diuretics, anticancer agents, contraceptive drugs, treatment of heart disease, and anti-glaucoma agents. γ-Butyrolactone moiety is also found in a variety of biologically active experimental drugs [1,2,3,4] and synthetic intermediates [5,6,7,8,9,10]. Moreover, numerous natural products, showing diverse biological activities, have γ-butyrolactone moiety.
The most universal synthetic method for γ-butyrolactone is intramolecular esterification, which can be readily utilized with substrates bearing γ-hydroxybutanoic acid functionality. However, diverse synthetic methodologies have been developed based on the discovery of biologically active synthetic or natural lactone drugs. Consequently, there have been many efforts to develop efficient synthetic methods to construct γ-butyrolactone, and several focused reviews have been published [11,12,13,14]. For example, Taylor and colleagues summarized new synthetic approaches for α-methylene-γ-butyrolactones [12] and Marstral, Feringa and colleagues reviewed the catalytic asymmetric synthesis of γ-butyrolactone [13].
In this review, we first prepare a brief introduction of biologically active γ-butyrolactones including eight FDA-approved drugs (Table 1) and various natural and synthetic γ-butyrolactones that have broad biological activities such as anticancer, anti-inflammatory, antibiotic, antifungal, antioxidant activities as well as immunosuppressive, neuroprotective, and hypoglycemic activities (Table 2). Additionally, we summarize synthetic methodologies for the construction of γ-butyrolactone reported from 2010 to 2020, which are depicted in seven main sections based on the sites of bond formation (Figure 1). Each section is further divided into subsections according to the type of reaction and contains a description focused on the reaction mechanism. Additionally, applications of the reaction to the synthesis of complex molecules are included to demonstrate the synthetic utility of the reactions. The synthetic methodology has been continuously improving over the past decade. Therefore, this review will provide an update of recent work in the development of synthetic methods for the construction of γ-butyrolactones.

2. Pharmacological Activities of γ-Butyrolactones

2.1. Approved Drugs

Several γ-butyrolactone-containing drugs have been FDA-approved and used in clinics for diverse purposes (Table 1). Pilocarpine, isolated from Pilocarpus microphyllus, is used to treat xerostomia and reduce eye pressure. (Entry 1) [15]. Pilocarpine is also widely applied to pharmacological research as a control cholinergic agonist. γ-Butyrolactone moiety was employed in a steroid skeleton at the C-17 position to develop steroidal aldosterone antagonists (Entry 2 and 3). Spironolactone and eplerenone are common medications for cardiovascular diseases such as high blood pressure and heart failure [16,17]. Drospirenone, structurally similar with spironolactone, is used to prevent pregnancy as a progesterone agonist. (Entry 4) [18]. Podophyllotoxin, a natural DNA topoisomerase inhibitor from Podophyllum peltatum, is treated to kill genital warts (Entry 5) [19]. Two semisynthetic derivatives of podophyllotoxin, etoposide, and teniposide, were approved as anticancer agents used for lymphoma, leukemia, and various solid tumors (Entry 6 and 7) [20,21]. Vorapaxar, a derivative of himbacine, is a first-in-class protease-activated receptor-1 (PAR-1) antagonist (Entry 8) [22]. By inhibiting PAR-1, vorapaxar reduces thrombotic cardiovascular events and the risk of myocardial infarction. Now, several γ-butyrolactone-containing drug candidates have been investigated in clinical studies for the treatment of heart disease, rheumatoid arthritis, and infectious disease.

2.2. Biologically Active γ-Butyrolactones

2.2.1. Anti-Inflammation

Diverse butyrolactones have been studied to evaluate anti-inflammatory activities (Entry 1–9 in Table 2). Some of these butyrolactones modulate the NF-κB signaling pathway such as a santonine-derived butyrolactone that showed anti-inflammatory activity through the inhibition of the ubiquitin-conjugating enzyme, UbcH5c (Entry 1 in Table 2) [23,24]. This anti-inflammatory activity was maintained in vivo using Freund’s adjuvant arthritis rat model. A novel phthalide-based butyrolactone (Entry 2) [25,26] and two natural products—calcaratarin D (Entry 3) [27] and a sesquiterpene lactone (Entry 4) [28]—were also reported to inhibit activity of the NF-κB signaling pathway and showed anti-inflammatory activity. Among them, the in vivo activity of the first butyrolactone (Entry 2) was evaluated against the adjuvant arthritis rat. Moreover, a biyouyanagin derivative attached to adenine (Entry 5) [29] and arctiidilactone (Entry 6) [30] showed anti-inflammatory activity through the inhibition of LPS-induced cytokine production or LPS-induced NO production, respectively. A COX-2 inhibitor (Entry 7), which is an indole-based γ-butyrolactone, was reported to have shown anti-inflammatory activity with an IC50 value of <0.001 μM [31]. CD10847 (Entry 8) [32] and cinatrin C3 (Entry 9) [33] exhibited potent anti-inflammatory activities via inhibition of caspase-1 or phospholipase A1, respectively.

2.2.2. Anticancer

The development of anticancer drugs is one of the long-term goals in the drug development field. Diverse natural and synthetic butyrolactones have been evaluated for their cytotoxic activities against various cancer cell lines. Protelichesterinic acid (Entry 10), a metabolite isolated from Antarctic lichens, showed cytotoxicity against HCT-116 cells with an IC50 value of 34.3 μM [34]. P. K. Roy and colleagues isolated one of the cembrane-type butyrolactones (Entry 11) from the soft coral, Lobophytum, which displayed a strong cytotoxic activity against RAW 264.7 cells [35]. Sasaki and colleagues evaluated the AKT inhibitory activities of lactoquinomycin (Entry 12) [36,37], kalafungin (Entry 13) [36,38], and frenolicin B (Entry 14) [36,39], classified as pyranonaphthoquinone lactones, which were originally reported as antibiotics. These butyrolactones exhibited strong AKT inhibitory activities with IC50 values of 0.149 μM~0.313 μM as well as cytotoxic activities with IC50 values of 0.05 μM~0.07 μM in MDA468 cells. A cytotoxicity of synthetic butyrolactones has been reported as well. Lee and colleagues synthesized an adenine-linked butyrolactone (Entry 15) which exhibited a cytotoxicity with an ED50 value of 0.3 μg/mL in L1210 cells [40]. Another example of synthetic butyrolactone, reported by Huth and colleagues, displayed strong HSP90 inhibitory activity (Ki = 1.9 μM) which could result in the development of anti-cancer agent (Entry 16) [41].

2.2.3. Antibiotic

Many γ-butyrolactone-containing small molecules have been studied in the development of antibiotics. Lactivicin (Entry 17) [42,43], produced by two strains of bacteria, and one bicyclic butyrolacone (Entry 18) [44] showed strong inhibition of β-lactamase with IC50 values of 2.4 μg/mL and 15 μg/mL, respectively. Moreover, various synthetic γ-butyrolactones exhibited potent antibacterial activities. For example, a synthetic α-amino-γ-lactone ketolide (Entry 19) showed excellent antibacterial activity against erythromycin-susceptible Streptococus pyogenes [45]. Additionally, hydrazonothiazolyl derivative (Entry 20) [46], β-cyclocitral derivative (Entry 21) [47], and α-methylene-γ-butyrolactone (Entry 22) [48] displayed potent antibacterial activities and a synthetic β-aryl-δ-iodo-γ-butyrolactone (Entry 23) exhibited bactericidal activity against Proteus mirabilis [49,50].

2.2.4. Antifungal

Researchers found that α-methylene-γ-butyrolactone ring is a natural pharmacophore for antifungal natural products (Entry 24) [51]. Various synthetic α-methylene-γ-butyrolactone analogues were synthesized and evaluated as potent antifungal agents. Feng’s groups and Xing’s groups found that α-methylene-γ-butyrolactones bearing aromatic moiety at γ-position exhibited antifungal activity against Colletotrichum lagenarium (Entry 25,26) [52,53]. Höfle and colleagues isolated complex γ-butyrolactone natural product, leupyrrin A1 (Entry 27) from Sorangium cellulosum and found its potent antifungal activity [54]. Menche and colleagues reported the first total synthesis of leupyrrin A1 and SAR studies of leupyrrin analogues as potent antifungal agents [55,56].

2.2.5. Immunosuppressive

Two synthetic γ-butyrolactones and two natural products were reported to show immunosuppressive activities. Yang and colleagues found that benzene-fused γ-butyrolactones (Entry 28) demonstrate highly efficacious immunosuppressive properties [57]. A sesquiterpene lactone, isolated from Artemisia argyi (Entry 29), also exhibited potent immunosuppressive activity, which was assessed via inhibitory effect on the proliferation of T lymphocytes [58]. A santonin derivative (Entry 30) reported by Chinthakindi and colleagues is another example of the immunosuppressant evaluated by T- and B-cell proliferation assay [59]. A natural γ-butyrolactone kinsenoside (Entry 31), originally isolated from Anoectochillus roxburghii, was reported as a potentially effective drug for treating patients with autoimmune hepatitis via targeting VEGFR2 to reduce the interaction between PI3K-AKT and JAK2-STAT pathways, which was confirmed in the vaccinated mouse model [60,61].

2.2.6. Neuroprotective

Recent studies found that natural and synthetic γ-butyrolactones can be useful in the treatment of neurodegenerative disorders. Zhu and colleagues showed phenolic γ-butyrolactones in Cinnamomum cassia (Entry 32) exhibit a neuroprotective effect against tunicamycin-induced cell death in human dopaminergic neuroblastoma SH-SY5Y cells [62]. Guo and colleagues conducted similar studies and found that japonipene C (Entry 33) is responsible for the neuroprotective effect of the extract of Petasites japonicas [63]. Bi and colleagues revealed that the γ-butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3H)-one (3BDO; Entry 34) protects against Aβ25-35-induced cytotoxicity in the PC12 cell. 3BDO was proposed to exhibit the protective effect by inhibiting ROS production and autophagy process [64]. In vivo assay was performed to evaluate memory rescuing activity as well as the Aβ lowering activity of 3BDO in mouse brain [65]. These findings show γ-butyrolactone can be utilized as potential therapeutic scaffold for the treatment of Parkinson’s disease and Alzheimer’s disease.

2.2.7. Antioxidant

The antioxidant activity of γ-butyrolactones has been verified using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and superoxide scavenging assay. Lee and colleagues studied the antioxidant activity of styraxlignolide E (Entry 35) in Styrax japonica [66]. Boustie and colleagues found that norstictic acid (Entry 36) isolated from Usnea articulate shows superoxide scavenging activity higher than the well-known antioxidant quercetin [67]. The result suggested that this activity is involved in the antioxidant defense of lichens.

2.2.8. Hypoglycemic

The hyperglycemic activity of γ-butyrolactones has recently attracted attention as a possible therapeutic agent for type 2 diabetes. Lin and colleagues revealed that butyrolactone-1 (Entry 37) inhibits α-glucosidase in vitro and shows a potent TNF-α lowering effect [68]. The binding between butyrolactone-1 and α-glucosidase was theoretically proved in a molecular docking study. In an in vivo study on mice, potent hyperglycemic activity was maintained. Xiao and colleagues synthesized the analogues of butyrolactone-1 by modifying side chains (Entry 38) [69]. A biological evaluation showed that butyrolactone-1 derivatives display inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) which is a promising therapeutic target of type 2 diabetes.

3. Synthesis of γ-Butyrolactones

3.1. Synthesis of γ-Butyrolactone via C5-O1 Bond Formation

3.1.1. Oxidative Lactonization of Pentenoic Acid

The oxidative lactonization of alkenoic acid is one of the most popular transformations for the synthesis of lactone. A typical approach is usually initiated with the oxidation of olefin catalyzed by the highly toxic and expensive transition metal via the Prévost−Woodward reaction and Upjohn reaction conditions, and the subsequent intramolecular nucleophilic addition of carboxylic acid [70,71,72]. In contrast, recently reported methods for oxidative lactonization claimed metal-free and less toxic conditions, which utilized cheap and green organic catalysts and oxidants. These reactions have been developed with a view toward green chemistry.
In 2012, Gade and colleagues reported the triflic acid (TfOH)-catalyzed oxidative lactonization using peroxyacid as an oxidant (Figure 2) [73]. The cascade epoxidation of olefin 1 with peracetic acid and an intramolecular epoxide opening reaction provided γ-butyrolactone 2. TfOH was proposed as a catalyst in both the ring-opening reaction via epoxide activation and acetylation of the subsequent hydroxyl group of γ-butyrolactone [74]. This method was applied to intramolecular lactonization as well as the intermolecular diacetylation of olefins. Considering the convenient process and the broad substrate scope, this might be an alternative approach to osmium tetroxide-catalyzed dihydroxylation of alkenes.
Kang and colleagues also developed the TfOH-catalyzed oxidative lactonization of alkenoic acid 3 (Figure 3) [75]. Instead of peroxyacetic acid, sodium periodate was used as an oxidant. This method showed a high tolerance for a broad range of α,β-substituted pentenoic acid, providing the corresponding γ-butyrolactones 4 and bicyclic lactone scaffolds.
Furthermore, Kokotos and colleagues developed an oxidative lactonization catalyzed by an organocatalyst, which relied on the use of hydrogen peroxide as the oxidant with 2,2,2-trifluoroacetophenone 5 as the organocatalyst (Figure 4) [76]. Mild reaction conditions led to an environmentally and industrially friendly process.
The oxidative ring contraction strategy from 3,4-dihydropyran-2-ones 6 developed by Legault and colleagues using hypervalent iodine has been shown to provide 3,4-trans-γ-butyrolactones 7 (Figure 5) [77]. The authors suggested that the hyperiodine reagent selectively reacts with trans-face to β-substituents of 6. This face selectivity generates iodinated intermediate 8 and the subsequent attack of a water molecule at the carbonyl position affords intermediate 9. γ-butyrolactone 7 was diastereoselectively obtained through intramolecular substitution by carboxylic acid. The development of an enantioselective protocol was evaluated using a specific chiral iodine reagent.
As an analogous approach to oxidative lactonization, Dodd and colleagues reported aminolactonization with the use of in situ-generated nosyliminoiodane (Figure 6) [78]. The Cu-catalyzed generation of nitrene from arylsulfonyliminoiodane 10 was reported to yield aziridines from alkene groups [79,80]. For example, the aziridine intermediate 11, generated after the metal-catalyzed reaction of t-butyl ester 12 with iminoiodane 10, was successfully transformed into a high yield of amino γ-butyrolactone 13. The usefulness of this aminolactonization was exemplified by further annulation of butyrolactone in novel complex heterocyclic systems (Figure 6, bottom).

3.1.2. Halolactonization of Pentenoic Acid

The halolactonization of alkenyl carboxylic acids is widely used to construct functionalized lactone skeletons, including γ-butyrolactone. Generally, electrophilic NXS (e.g., NBS or NIS) and halogens are utilized to activate olefin moieties [81,82].
In 2011, Togo and colleagues developed a sustainable electrophilic bromine source via umpolung of alkali metal bromide [83]. Bromide (Br-) from potassium bromide, one of the most abundant and stable bromide sources, is oxidized into bromonium ion (Br+) 14 by oxidation with Oxone. Encouraged by the success of intramolecular bromo-amination with in situ-generated bromonium ion, the use of this umpolung system in the bromolactonization of 4-pentenoic acid 15 has been investigated, resulting in the production of γ-butyrolactone moieties 16 (Figure 7) [84]. At this stage, the preference of the diequatorial conformation of the transition state over the diaxial form results in the diastereoselective production of cis-isomer 16. The utility of this approach was demonstrated by the total synthesis of dubiusamin C 19 from bromo butyrolactone 18, which was obtained by the bromolactonization of pentenoic acid 17.
Kumar and colleagues reported selenium-catalyzed bromolactonization by applying isoselenazolone 20 as a catalyst (Figure 8) [85]. Organoselenium compounds react with bromine to generate reactive bromoselenium intermediate 21, which has a greater reactivity than NBS and molecular bromine (Br2) [86]. Several NMR studies confirmed that seleno-intermediate 21 plays a key role in the transfer of Br+ to the olefins of 22. Intermediate 21 is catalytically regenerated in the presence of bromine or NBS with an inorganic base. This reaction allowed access to the construction of bromo butyrolactone 23 from a broad scope of pentenoic acids 22.

3.1.3. Acid-Promoted Cyclopropane Opening

The electrocyclic ring-opening reaction of cyclopropane has been demonstrated as a powerful tool for the construction of fused cyclic systems with sequential intramolecular trapping [87]. Several acid-catalyzed, domino cyclopropane opening/carboxylic acid trapping reactions have been investigated to construct fused-butyrolactone systems.
In 2017, Reddy and colleagues reported a Brønsted acid-catalyzed cascade reaction for the construction of a tricyclic structure 26 bearing a γ-butyrolactone core (Figure 9) [88]. This interesting reaction starts with p-toluenesulfonic acid (PTSA)-catalyzed aldol condensation of diketone 24 to afford bicyclic enone 25, which subsequently undergoes acid-catalyzed cyclopropane opening/intramolecular trapping by an ester moiety.
A similar domino reaction of silver (I)-mediated activation of dibromocyclopropane 27/intramolecular acid trapping was developed by Batey and colleagues to form a trans-fused bicycle 28 possessing γ-butyrolactone (Figure 10) [89]. A unique trans-fused [5.3.0]-system presented in pseudoguainolide natural products was selectively obtained. Computational studies demonstrated the preference of a trans-fused system over a cis-fused system.

3.1.4. Au-Catalyzed Oxaallylation

Gold-catalyzed allylic functionalization has been the object of diverse cyclization reactions and has been found to be efficient for the preparation of γ-butyrolactone [90,91,92]. Chen and colleagues examined the Au-catalyzed lactonization of allylic acetate 29 to construct a butyrolactone system (Figure 11) [93]. The proposed mechanism involved the generation of an allylic cation intermediate 30 from allylic acetate 29 in the presence of the Au catalyst. The subsequent nucleophilic attack by the ester moiety resulted in the formation of bicyclic γ-butyrolactone 31.
Bandini and colleagues reported the direct activation of free allylic alcohol 32 by applying a gold catalyst with N-heterocyclic carbene (Figure 12) [94]. An allylic cation intermediate is generated upon coordination of the NHC-gold complexes to a free allylic alcohol 32. The resulting poly-substituted γ-butyrolactone 33 was obtained via nucleophilic attack by ester and subsequent dealkylation.
More recently, Aponick and colleagues developed a gold-catalyzed oxa-allylation of a free allyl alcohol 34 with an intramolecular free carboxylic acid to prepare γ-butyrolactone 35 (Figure 13) [95]. In contrast to Brønsted acids generating a 7-membered lactone skeleton 36 via direct acid-catalyzed esterification, γ-butyrolactone 35 was obtained using a transition-metal catalyst via an SN2′-type oxa-allylation mechanism.
Allenylglycine 37 was also used as a precursor for the construction of γ-butyrolactone 38. Ohfune and colleagues applied the Au-catalyzed intramolecular lactonization into the allene system 37, which is a useful substrate for gold catalysis (Figure 14) [96]. Interestingly, γ-butyrolactone 38 was obtained regio- and diastereoselectively via 5-endo-dig cyclization in the presence of bulky TBS at the allenic terminal carbon.

3.1.5. Photoredox-Catalyzed Lactonization

Photoredox catalysis through single-electron transfer (SET) has attracted significant attention in the community of organic chemistry. Not surprisingly, the application of photoredox catalysis to the ring formation reaction, including γ-butyrolactone synthesis, has been intensively explored. As shown in Table 3, several synthetic approaches have been reported to provide 5,5-disubstituted γ-butyrolactone.
Photoredox-catalyzed γ-butyrolactone synthesis generally starts with radical generation through the reduction of radical precursors 39 (e.g., diazonium salt, N-hydroxylphthalimide ester, etc.) by the oxidative quenching of the excited state of the photocatalyst (PC *). The in situ-generated radical 40 adds to the alkene of 41 to produce intermediate 42, which is transformed to carbocation 43 through single-electron transfer (SET) with an oxidized photocatalyst (PC+). Nucleophilic attack of the carboxylic acid results in the γ-butyrolactone 44 (Figure 15). Aryl diazonium salts (Entry 1) [97], Umemoto’s reagent (Entry 2) [98], N-hydroxylphthalimide ester (Entry 3) [99], and α-bromo ester [100] were used in these reactions.

3.2. Synthesis of γ-Butyrolactone via C4-C5 and C2-O1 Bonds Formation

Connecting the C4-C5 bond in [3 + 2] annulation-type γ-butyrolactone formation is one of the most promising routes. Retrosynthetically, the disconnection of the C4-C5 and C2-O1 bonds gives a3 and a2 synthons; thus, this mismatched relationship should be overcome through a certain umpolung reaction.

3.2.1. Transition-Metal Catalyzed C-C Bond Coupling

Krische et al. applied their transfer hydrogenative C-C bond coupling chemistry to the γ-butyrolactone syntheses. In 2012, they reported that the iridium-catalyzed carbonyl 2-(alkoxycarbonyl)allylation between various primary alcohols 45 and acrylic ester 46 afforded γ-substituted α-exo-methylene-γ-butyrolactone 47 with high enantioselectivity (Figure 16) [101]. As shown in the mechanism, this transformation involves an a3–d3 umpolung process regarding the β-position of the acrylate counterpart 46, which normally acts as an electrophile during C-C bond-forming reactions [102].
In the C-C bond constructing catalytic transfer hydrogenation, a secondary alcohol was not a suitable partner of acrylates because of the low susceptibility to the nucleophilic attack [103] of the π-allyl complex derived from the acrylates. Just a year after their first report, Krische and colleagues also revealed that ruthenium(0)-catalyzed hydrohydroxyalkylation of acrylates with vicinal diols or their oxidized congeners could provide a series of γ-butyrolactones, including spiro-γ-butyrolactones (Figure 17a), polysubstituted 2,3′-spirooxindole-γ-butyrolactones (Figure 17b), and α-exo-methylene-γ-butyrolactones (Figure 17c) [104]. As illustrated in Figure 17d, 1,2-diol 48 and its highly oxidized congeners 49 and 50 were transformed into the same outcome 51, indicating that this transformation proceeds in a redox level-independent manner.
The asymmetric synthesis of α-exo-methylene γ-butyrolactones was developed by Zhang and colleagues in 2015 (Figure 18) [105]. This methodology utilized an enantioselective chromium-catalyzed carbonyl 2-(alkoxycarbonyl)allylation of a wide range of aldehydes. To achieve superior enantioselectivity, the C2 symmetric bisoxazoline ligand was essential. Rigidification of Guiry’s tridentate ligand [106] provided a new ligand 52, which resulted in excellent enantiomeric excess of up to 99%. Similar to the previous methods [101,104], the inherent positive character of the acrylate β-position was inverted via the cobalt-assisted generation of allyl-chromium species 53. To demonstrate the synthetic utility, the total synthesis of an antitumor and antimicrobial natural product, (+)-methylenolactocin 54, was successfully conducted with a 53% overall yield over three steps and 92% ee. (Figure 18, bottom).
Spirooxindoles [107] and α-exo-methylene-γ-butyrolactones [12,108], biologically relevant structural motifs, have received attention from medicinal chemists. In this regard, the fusion of two scaffolds would be a promising strategy for securing biologically active scaffolds. In 2013, the first asymmetric synthesis of 2,3′-spirooxindole-α-exo-methylene γ-butyrolactone 57 via the indium(III)-catalyzed allylation of isatins 55 and β-amido allylstannanes 56 was reported (Figure 19) [107,109]. The amide NH proton of allylstannanes was essential for enhancing enantioselectivity as well as complete conversion by engaging in six-coordinated indium complex 58 with tridentate ligand 59, thereby inducing 56 to approach from Re-face [109]. The resulting acyclic 2-oxindoles 60 was cyclized under acidic conditions to afford the desired lactone 57 with complete stereochemistry retention.

3.2.2. NHC-Catalyzed C-C Bond Coupling

A chiral N-heterocyclic carbene (NHC) has played an important role in making a homoenolate nucleophile from enals through the a3–d3 umpolung reaction [110]; thus, it has been widely used in the optically active γ-butyrolactone synthesis via [3 + 2] annulation. Over the last decade, this strategy has been employed to construct a 2,3′ spirooxindole-γ-butyrolactone system.
In 2011, Ye and colleagues discovered the first enantioselective NHC-catalyzed synthesis of spirooxindole-γ-lactone with isatin and an enal as substrates (Figure 20a) [111]. A chiral NHC 61 derived from l-pyroglutamic acid displayed the best result, affording the desired spirolactone up to 99% ee. A proximal hydroxy group in 61 was crucial to obtain the lactone with an excellent yield and enantioselectivity because the hydrogen bonding between the carbonyl group of isatin and the catalyst hydroxy group may guide the direction of the isatin approach and enhance its reactivity.
A year later, a similar NHC-catalyzed transformation was carried out in the presence of lithium chloride as an external activator. Scheidt and colleagues revealed that the addition of two equivalents of LiCl to the reaction gave the beneficial effect of creating an organized transition state with 62, which offered excellent enantioselectivity, similar to the role of the internal hydroxy group of 61 in the previous method (Figure 20b) [112].
In 2015, it was independently disclosed by Chi (Figure 20c) [113] and Yao (Figure 20d) [114] that aliphatic acids could participate in the NHC-catalyzed spiro-γ-lactone construction instead of the aldehyde substrates. The key to this modification was the in situ pre-activation of carboxylic acid by various peptide coupling reagents, which enabled the formation of a common NHC-coupled homoenolate intermediate.
Finally, Xu and colleagues reported that the saturated aryl ester 64 was also able to engage in this type of NHC-catalyzed asymmetric annulation with catalytic amount of 1-hydroxybenzotriazole (HOBt) (Figure 20e) [115]. After the experimental studies, it was revealed that HOBt had a dual role: activation of the ester for the next substitution by the chiral NHC, and the stabilization of the effective transition state via hydrogen bonding.
A chiral NHC led to significant advances in dynamic kinetic resolution (DKR)-mediated asymmetric transformation. In 2015, Johnson and colleagues developed the first intermolecular DKR between α,β-unsaturated aldehydes and racemic β-halo-α-keto esters 65, which installed three stereocenters during the single bond-forming process (Figure 21) [116]. Using this strategy, they obtained 3,4,4-trisubstituted γ-butyrolactones 66 with three contiguous stereocenters in a single operation, with excellent enantioselectivity (up to 98% ee).

3.2.3. Photoredox-Catalyzed C-C Bond Coupling

Photoredox catalysis achieves the cutting-edge evolution in the C-H bond activation chemistry; thus, it enables not only mild, economical, and environmentally friendly chemical reactions, but also the discovery of unprecedented reactivity of chemical bonds [117]. In 2015, MacMillan’s seminal work demonstrated that the α-C–H bond of alcohols could by selectively activated in the presence of allylic, benzylic, α-C=O, and α-ether C-H bonds. In addition, the corresponding α-hydroxyl radical participated in the formation of the γ-lactones with methyl acrylate (Figure 22) [118]. The C–H bond-weakening, assisted by hydrogen bond, gave rise to the unique selectivity, which was supported by tetra-n-butylammonium phosphate as a catalytic H-bond acceptor. The versatility of this methodology was demonstrated by testing several structurally complex substrates 68–75 containing inherently activated C–H bonds (Figure 22, bottom).
Recently, the greener variant of typical photoredox catalysis, the photo-organocatalytic synthesis of this lactone has been accomplished by Kokotos and colleagues. (Figure 23) [119]. By utilizing a readily available and cheap photoinitiator, phenylglyoxalic acid 76 as an alternative to transition metal catalysts, a variety of primary and secondary alcohol 77 and a maleic acid diester 78 merged into the corresponding γ-butyrolactones 79 in the presence of visible light from sunlight or simple household lamps. Through extensive mechanistic studies, it was proposed that photoinduced exciplex 80 formation facilitates selective hydrogen atom abstraction from the secondary alcohol.

3.2.4. Miscellsious γ-Butyrolactone Formation

Electroreduction of carbonyl compounds can convert electrophilic carbonyl compounds into nucleophilic carbanion, which is further involved in the [3 + 2] coupling of γ-butyrolactones. In this regard, electroreductive C-C coupling of α,β-unsaturated carbonyl compounds with ketones or aldehydes has been known to be useful for the synthesis of γ-butyrolactones. A previous electroreductive method [120] toward lactones in the presence of trimethylsilyl chloride (TMSCl) was improved by Kise and colleagues by means of a chiral auxiliary, leading to optically active 4,5,5-trisubstituted γ-butyrolactones 83 in high diastereoselectivity (Figure 24) [121]. The reaction is initiated with two-electron transfer to a more reducible diaryl ketone 82. The resulting carbanion 84 is diastereoselectively coupled with the Michael acceptor 81. DFT calculations for the bond-forming transition states explained the reason for its Si-face preference.
The synthesis of 3,3′-spirooxindole-γ-butyrolactones, another isomeric form of the spirooxindole-γ-lactone motif, has attracted less attention, but it is still valuable when it comes to the longstanding need to secure a structurally diverse chemical library in the drug discovery field. In 2017, Du and colleagues revealed that the peptide coupling reagent (PCR)-assisted β-functionalization of indoline-2-one aliphatic acids 85 could produce the desired spirofused γ-lactone 86 and 87 via [3 + 2] coupling with electrophilic carbonyl substrates; isatins 88 or trifluoromethyl ketones 89 (Figure 25) [122]. After the intensive screening of the reaction conditions, it was found that the optimal PCR was HATU for isatin substrates and CDI for trifluoromethyl ketone substrates.
In 2017, a one-pot multicomponent reaction was exploited to construct enantiomerically pure 4,5-disubstituted γ-butyrolactones 93 by Bhat and colleagues. (Figure 26) [123]. Their strategy was the organocatalyzed Knoevenagel condensation/Michael addition/decarboxylative lactonization cascade utilizing cheap and readily accessible starting materials such as Meldrum’s acid 90, aldehydes 91, hydroxyketones 92, and the chiral cinchona catalyst 94. Enamine (Z)-95, which has a chiral environment induced by 94, is subjected to asymmetric 1,4-addition with the Knoevenagel condensation adduct 96 to afford 97 bearing two contiguous stereogenic centers. This precisely designed three-component reaction was able to avoid possible side reactions such as aldol condensation products between 91 and 92.

3.3. Synthesis of γ-Butyrolactones via C3-C4 and C2-O1 Bond Formation

Connecting the C3-C4 bond in [3 + 2] annulation-type γ-butyrolactone formation has been less investigated than that of C4-C5 bond formation. Nevertheless, the development of this synthetic route is still significant, in that securing diverse synthetic tools has always been beneficial to organic chemists, particularly for complex natural product synthesis. Retrosynthetically, the disconnection of the C3-C4 and C2-O1 bonds gives d3 and d2 synthons; thus, this mismatched relationship should be overcome through a certain umpolung reaction.
A borrowing hydrogen methodology, also known as hydrogen autotransfer, is a subclass of a wide range of transfer hydrogenation chemistry similar to the aforementioned transfer hydrogenative C–C bond coupling [124,125]. Beller and colleagues reported that ruthenium (Ru) pincer catalyst 100 promoted γ-butyrolactone synthesis from 1,2-diols 98 and malonates 99 (Figure 27) [126]. Catalyst 100 temporarily abstracts hydrogen from 1,2-diols to give the corresponding α-hydroxyketone 101, which can act as an electrophile. This step belongs to a polarity inversion process at the C3 position of the resulting γ-lactones. Whereas the above-mentioned Ru-catalyzed spirolactonization consequentially delivers alcohol C–H functionalization type products (see Figure 17), this Ru-catalysis proceeds through a type of alcohol substitution, which offers monocyclic lactones.
An epoxide is a useful three-atom building block in the [3 + 2] annulation strategy because of its susceptibility to the attack of suitable carbon nucleophiles such as ester enolates. In 2017, ketene silyl acetal 102 was applied as the effective enolate equivalent to constructing the lactone via regioselective epoxide opening followed by lactonization (Figure 28) [127]. Additionally, an ionic liquid system composed of a mixture of 1,3-dimethylimidazolium fluoride ([Dmim]F) and 1-butylimidazolium tetrafluoroborate ([Hbim]BF4) was utilized to achieve the desired transformation. The catalytic amount of [Dmim]F acted as a Si-O bond activator and [Hbim]BF4 served as the solvent providing acidic media. This ionic liquid mixture was able to be reused up to three times, which is valuable for the contribution toward green chemistry.

3.4. Synthesis of Butyrolactone via C3-C4 and C5-O1 Bonds Formation

There are a few examples of this synthetic approach through the formation of C3-C4 and C5-O1 bonds during 2010 to 2020. Mostly, the single-electron transfer pathway is involved in the C3-C4 and C5-O1 bond formation approaches. First, photoredox catalysis was applied with alkenes and suitable counterparts such as α,β-unsaturated acid [128], oxime acid [129], or haloacetic acid [130]. Second, a metal oxidant-mediated transformation of glycals to γ-butyrolactones was reported [131]. Third, the copper-catalyzed-cyclopropanol ring-opening cross-coupling reaction was utilized to synthesize γ-butyrolactones containing quaternary carbon centers [132].

3.4.1. Polar Radical Crossover Cycloaddition (PRCC)

Polar radical crossover cycloaddition (PRCC) has been utilized in the construction of various saturated heterocycles, including tetrahydrofurans [133], γ-lactams, and pyrrolidines [134]. The co-catalyst of Fukuzumi acridinium single-electron photooxidant and a redox-active hydrogen atom donor is a key mediator of PRCC through photoredox catalysis. Nicewicz and colleagues extended the PRCC approach to the synthesis of γ-butyrolactones [128]. First, the oxidizable alkenes 103 and α,β-unsaturated acids 105 as nucleophiles forged γ-butyrolactones 107 under photoredox catalysis. As depicted in Figure 29, an electrophilic alkene cation radical 104 is formed by the excited acridinium-mediated single-electron oxidation followed by the generation of the radical intermediate 106 through the addition of carboxylic acid 105 to the alkene cation radical. 5-exo-trig radical cyclization and hydrogen atom transfer with thiophenol provided the desired γ-butyrolactones. Alternatively, α-amino-γ-butyrolactones 110 have also been synthesized by the PRCC method using oxidizable alkenes 108 and O-benzyloxime acids 109, which correspond to α,β-unsaturated acids 105 (Figure 30) [129].

3.4.2. Atom-Transfer Radical Addition (ATRA)

Another example of γ-butyrolactone synthesis mediated by photoredox catalysis is atom-transfer radical addition (ATRA), which was reported by Kokotos and colleagues in 2018 [130]. ATRA has been utilized as a powerful method for one-step C-C and C-X bond formation between olefins and haloalkanes. Kokotos and colleagues applied photoredox catalysis in ATRA using Ru(bpy)3Cl2 as a photoredox catalyst, which was employed in the conversion of alkenes 111 and α-iodoacetic acids 112 to γ-butyrolactones 113 under light irradiation. In this reaction, the excited photocatalyst is reduced by ascorbate, followed by reaction with α-iodoacetic acid 112 to generate the electrophilic radical 114, which reacts with the alkene leading to radical 115. Then, propagation proceeded with iodoacetic acid, resulting in the formation of 116. Finally, γ-butyrolactone 113 is formed by the deprotonated carboxylic acid under basic reaction conditions (Figure 31).

3.4.3. Mn(OAc)3-Mediated Radical Lactonization

Manganese (III) acetate has been utilized as a versatile single-electron transfer (SET) reagent. Mukherjee and colleagues reported Mn(OAc)3-mediated radical lactonization to synthesize carbohydrate-based γ-butyrolactones from glycals [131]. Under sonication, a variety of 1,2-glycals and 2,3-glycals were converted to γ-butyrolactones in a regioselective and stereoselective manner, which were governed by conformational preferences for glycal substrates (Figure 32).

3.4.4. Copper-Catalyzed Cyclopropanol Ring-Opening Cross-Coupling Reaction

Cyclopropanols 117 are versatile substrates in various ring-opening and ring-expansion reactions because of the intrinsic stain of the three-membered ring. One of the representative reactions in this class is the cyclopropanol ring-opening cross-coupling reaction mediated by diverse transition metal catalysts or single-electron transferring oxidants, resulting in the formation of a variety of β-substituted ketones. Formation of α,β-unsaturated enone byproducts, which are normally caused by β-hydride elimination of the metallo-homoenolate 120, is one of the major issues in this reaction. Interestingly, Dai and colleagues developed a method to accelerate α,β-unsaturated carbonyl byproduct 121 by adding potassium iodide in the reaction mixture and reacting with 2-bromo-2,2-dialkyl acetate 118 to obtain γ-butyrolactones 119 bearing quaternary carbon centers, which are catalyzed by Cu(OTf)2 (Figure 33) [132].

3.5. Synthesis of γ-Butyrolactones via C2-C3 and C2-O1 Bonds Formation

Carbon monoxide is used as a versatile C1 source in organic synthesis, thereby reacting with suitable unsaturated alcohols to afford various ring sizes of lactones [135]. There have been increasing reports of methodologies for producing γ-butyrolactones using carbonylations and hydroformylations over the past decades. However, due to the innate drawbacks of CO, including its high toxicity, gaseous nature, and strict regulations for transportation, bypassing the direct use of CO gas is another significant topic in carbonylation research [135].

3.5.1. Carbonylative Lactonization

Among various methodologies utilizing CO gas or other carbonyl sources, transition-metal-catalyzed carbonylative lactonization is most commonly used for γ-lactone formation. Iron pentacarbonyl is a cheap, practical surrogate of the carbonyl donor, and it was first applied to convert (amino)polyhydroxylated terminal olefins 122 into the bicyclic lactones 123 by Gracza and colleagues (Figure 34) [136]. In this system, a CO molecule is generated in situ by the assistance of copper(II) chloride and gentle heat, and subsequently participates in the palladium(II) catalysis cycle. Very recently, the same group showed that this protocol could be applicable to a continuous flow reaction in comparable yield with the batch reaction [137].
In 2014, Jiang and colleagues reported a unique one-pot-four-step cascade reaction in ionic liquid media by employing a palladium-catalyzed carboxylative annulation to construct highly functionalized γ-butyrolactones (Figure 35) [138]. This transformation is initiated from the trans-chloropalladation of alkynoates 124, of which the regioselectivity is governed by electronic factors. Intermediate 127 undergoes carbopalladation with butenol 125, followed by CO insertion and reductive elimination, yielding C3 functionalized γ-lactones 126 bearing a tetrasubstituted olefin unit. The imidazolium type ionic liquids played an important role during the reaction as a ligand of the palladium catalyst and as a chloride source [139]. They further demonstrated the utility of vinyl chloride functionalities in the products by employing them to Suzuki–Miyaura coupling and Negishi coupling.
Organic disulfides, which have been considered as inefficient substrates for transition-metal-catalyzed carbonylative heteroatom addition, were successfully used as counterparts of thiolated α-alkylidene-γ-butyrolactone synthesis in the presence of dicobalt octacarbonyl or palladium complexes such as Pd(PPh3)4 and Pd(OAc)2 (Figure 36) [140]. A variety of homopropagyl alcohols 128 and aryl disulfides produced the desired thiolated lactones 129 by both catalytic systems with high regio- and stereoselectivity (cis-isomer). Mechanistically, despite the difference in the order of metal-alkyne complexation, the presence of a hydroxy group plays a critical role in the regioselectivity of carbonyl insertion in both cases.
C-C bonds in cyclopropanols can be easily activated by a transition-metal catalyzed ring-opening process generating metal-homoenolate species, which possess the potential of structural diversification by engaging in Csp3-Csp2 and Csp3-Csp3 cross-coupling with various counterparts [141]. Dai and colleagues combined this palladium-catalyzed C-C bond activation reaction with conventional carbonylation, and successfully constructed synthetically challenging oxaspirolactone structure 130 (Figure 37) [142]. The usefulness of this strategy was demonstrated by total syntheses of α-levantanolide and α-levantenolide in two and four steps, respectively (Figure 37, bottom).

3.5.2. Hydroformylation-Oxidation

The hydroformylation of olefins is one of the extensively investigated classes of carbonylation, especially for industrial applications [143]. This reaction is also applicable to γ-butyrolactone syntheses by adding a formyl group to hydroxyalkenes and subsequent oxidation of the corresponding lactols. Although the carbonyl insertion step has been known to normally take place in the anti-Markovnikov direction, Breit and colleagues successfully converted 1,1-disubstituted homoallylic alcohols 131 into the desired γ-lactones 132 containing quaternary carbon at the α-position (Figure 38) [144]. The key to this achievement was the use of a phosphinite as a removable catalyst-directing group. Diphenylphosphinites 133 was formed via transesterification with a catalytic amount of Ph2POMe and the resulting phosphinite group-guided approach of the rhodium hydride complex afforded a favorable six-membered cyclic hydrometallation transition state 134.
The enantioselective hydroformylation of 1,1-disubstituted olefins has proven to be unproductive, presumably due to the steric repulsion of an olefin coordination with a metal center [145]. Very recently, Zhang and colleagues addressed this challenge by modifying conventional chiral ligands to more sterically demanding variants (Figure 39) [146]. Under the optimized conditions, the hydroformylation of allylic alcohol 135 occurred following the anti-Markovnikov rule in high ee values, producing the corresponding optically active lactol. The lactol was able to be transformed into not only the desired optically active lactone 136 via PCC oxidation, but also into the tetrahydrofuran derivative via reduction or allylation.

3.5.3. Carboxylation-Lactonization

Carbon dioxide is the most abundant C1 source on earth; thus, harnessing this molecule would be appealing with respect to the development of economical and environmentally friendly synthetic methods. Nevertheless, due to the chemically inert nature of CO2 gas, carboxylation (CO2 activation) has been less widespread than carbonylation (CO activation). The nickel-catalyzed methyl-carboxylation of homopropagylic alcohols 137 met this demand, affording α-alkylidene-γ-butyrolactones 138 in a regio- and stereoselective manner (Figure 40) [147]. Ma and colleagues discovered that this catalytic system only required 1 mol % of Ni catalyst for CO2 activation and proceeded with broad functional group tolerance. The excellent regioselectivity may derive from the directing effect of the adjacent hydroxy group. The potential of this methodology was illustrated through the first total synthesis of (±)-heteroplexisolide E 139 [148].

3.6. Synthesis of γ-Butyrolactones via C3-C4 Bond Formation

C-H Insertion

Over the past several decades, Rh-catalyzed intramolecular C-H insertion has been intensively investigated and established as a powerful tool for the construction of structurally diverse cyclic compounds. Unsworth and colleagues reported a one-pot C-H insertion/olefination sequence to afford α-alkylidene-γ-butyrolactones (Figure 41) [149]. Rh-catalyzed C-H insertion of diazo compound 140 gave α-phosphonated γ-lactone 141, which was subsequently converted to α-alkylidene-γ-lactone 142 via Horner–Wadsworth–Emmons-type olefination. A variety of γ-lactones were obtained in a one-pot procedure in useful yields. The versatility of this protocol was demonstrated by the successful synthesis of natural products, cedamycin A, B, and eudesmanolide [150,151].

3.7. Synthesis of γ-Butyrolactones via Oxidative C2-O1 Bond Formation

A simple γ-butyrolactone is itself a broadly used material [152] as a solvent, extraction agent, and intermediate for polymers, pharmaceutics, herbicides, rubber production, etc. The oxidative lactonization of 1,4-butanediol under an efficient catalytic system has been a dominant industrial process because of its significant advantages [152]. This method does not produce any waste except for reusable hydrogen gas. Additionally, 1,4-butanediol can be obtained from renewable biomass such as glucose [153]. For these reasons, it is not surprising that many researchers have intensively modified this route to be more efficient and environmentally benign than conventional methods. The representative oxidative lactonization conditions recently developed for the synthesis of γ-butyrolactones from 1,4-butanediol are summarized in Table 4.
Ijms 22 02769 i055.

4. Conclusions

γ-Butyrolactones have been broadly studied in drug discovery, resulting in the identification of diverse biologically active small molecules containing γ-butyrolactone. Moreover, significant efforts to develop efficient and concise synthetic strategies toward γ-butyrolactone moiety have been reported in recent years utilizing readily available starting materials and newly developed reactions. The construction of diverse biologically active natural products and synthetic pharmaceuticals bearing γ-butyrolactone are allowed with these novel strategies. This review includes a brief overview of biologically active γ-butyrolactones and a summary of the representative synthetic methodologies toward γ-butyrolactones developed between 2010 and 2020, which are classified in the seven sections based on the sites of bond formation (Table 5) and described their reaction mechanism and further application in the synthesis of biologically active molecules. This update will help to develop biologically active new γ-butyrolactones and to solve hurdles in the synthesis of γ-butyrolactone-bearing natural products and pharmaceuticals as well as to develop novel synthetic approaches toward γ-butyrolactones.

Author Contributions

Conceptualization, J.H., J.J. and J.S.; writing-original draft preparation, J.H., J.J. and J.S.; writing—review and editing, J.H., J.J. and J.S.; supervision, J.J. and J.S.; funding acquisition, J.S. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by Korea government (MSIT) (No. 2020R1G1A1102355) and research fund of Chungnam National University.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

We thank all the researchers cited in this review. We are exceedingly grateful for the invitation to contribute to this Special Issue.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

[C2O2 mim]Cl1-carboxymethyl-3-methylimidazolium chloride
AcAcetyl
acacAcetylacetone
AcrAcridinium
ArAryl
ATRAAtom-transfer radical addition
BnBenzyl
Boctert-Butyloxycarbonyl
bpy2,2′- bipyridine
BuButyl
CDICarbonyldiimidazole
cod1,5-Cyclooctadiene
CpCyclopentadienyl
DBU1,8-Diazabicyclo(5.4.0)undec-7-ene
DCE1,2-Dichloroethane
dF(CF3)ppy2-(2,4-Difluorophenyl)-5-(trifluoromethyl)pyridine
DFTDensity functional theory
DKRDynamic kinetic resolution
Dmim1,3-Dimethylimidazolium
DMSODimethyl sulfoxide
DPPP1,3-Bis(diphenylphosphino)propane
dtbbpy4,4′-Di-tert-butyl-2,2′-bipyridine
EDC1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide
EtEthyl
FMOFlavin-containing monooxygenase
HATHydrogen atom transfer
HATU1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium3-oxide hexafluorophosphate
Hbim1-Dutylimidazolium
HLADHHorse liver alcohol dehydrogenase
HOBt1-Hydroxybenzotriazole
LEDLight-emitting diode
MeMethyl
MesMesitylene
MSMolecular sieve
NBSN-Bromosuccinimide
neocNeocuproine
NHCN-heterocyclic carbene
PcPhthalocyanine
PCCPyridinium chlorochromate
PCRPeptide coupling reagent
PETPhotoinduced electron transfer
PhPhenyl
PhenPhenanthroline
PrPropyl
PRCCPolar radical crossover cycloaddition
PTSAp-Toluenesulfonic acid
SETsingle-electron transfer
TBAFTetra-n-butylammonium fluoride
TBAPTetra-n-butylammonium phosphate
TBStert-Butyldimethylsilyl
TEATriethylamine
TEMPO2,2,6,6-Tetramethylpiperidin-1-yl)oxyl
TfTrifluoromethanesulfonyl
TFAtrifluoroacetic acid
THFtetrahydrofuran
TMBTP(-)-2,2′,5,5′-tetramethyl-3,3′-bis(diphenylphosphine)-4,4′-bithiophene
TMSTrimethylsilyl
Tsp-Toluenesulfonyl

References

  1. Omura, S.; Tanaka, H.; Okada, Y.; Marumo, H. Isolation and structure of nanaomycin D, an enantiomer of the antibiotic kalafungin. J. Chem. Soc. Chem. Commun. 1976, 213, 320–321. [Google Scholar] [CrossRef]
  2. Yamawaki, M.; Nishi, K.; Nishimoto, S.; Yamauchi, S.; Akiyama, K.; Kishida, T.; Maruyama, M.; Nishiwaki, H.; Sugahara, T. Immunomodulatory effect of (-)-matairesinol in vivo and ex vivo. Biosci. Biotechnol. Biochem. 2011, 75, 859–863. [Google Scholar] [CrossRef] [PubMed]
  3. Zhangabylov, N.S.; Dederer, L.Y.; Gorbacheva, L.B.; Vasil’eva, S.V.; Terekhov, A.S.; Adekenov, S.M. Sesquiterpene lactone arglabin influences DNA synthesis in P388 leukemia cells in vivo. Pharm. Chem. J. 2004, 38, 651–653. [Google Scholar] [CrossRef]
  4. Rudolphi, K.; Gerwin, N.; Verzijl, N.; van der Kraan, P.; van den Berg, W. Pralnacasan, an inhibitor of interleukin-1β converting enzyme, reduces joint damage in two murine models of osteoarthritis. Osteoarthr. Cart. 2003, 11, 738–746. [Google Scholar] [CrossRef] [Green Version]
  5. Chowdhury, R.; Ghosh, S.K. Organo-catalyzed enantioselective synthesis of some β-silyl γ-alkyl γ-butyrolactones as intermediates for natural products. Tetrahedron Asymmetry 2011, 22, 1895–1900. [Google Scholar] [CrossRef]
  6. Ok, T.; Jeon, A.; Lee, J.; Jung, H.L.; Chang, S.H.; Lee, H.S. Enantiomerically pure synthesis of β-substituted γ-butyrolactones: A key intermediate to concise synthesis of pregabalin. J. Org. Chem. 2007, 72, 7390–7393. [Google Scholar] [CrossRef] [PubMed]
  7. Brown, E.; Daugan, A. An easy preparation of (-) and (+)-β-piperonyl-γ-butyrolactones, key-intermediates for the synthesis of optically active lignans. Tetrahedron Lett. 1985, 26, 3997–3998. [Google Scholar] [CrossRef]
  8. Bielitza, M.; Pietruszka, J. An enantioselective Mukaiyama aldol reaction as the key step towards the tetrahydropyran core of psymberin via a γ-butyrolactone intermediate. Synlett 2012, 23, 1625–1628. [Google Scholar]
  9. Givens, R.S.; Oettle, W.F. Photorearrangement of a γ-butyrolactone: Generation of intermediates in photochemical reactions. Anal. Proc. 1969, 1164–1165. [Google Scholar] [CrossRef]
  10. Vinet, L.; Zhedanov, A. A “missing” family of classical orthogonal polynomials. J. Phys. A Math. Theor. 2011, 44, 51. [Google Scholar] [CrossRef]
  11. Murauski, K.J.R.; Jaworski, A.A.; Scheidt, K.A. A continuing challenge: N-heterocyclic carbene-catalyzed syntheses of γ-butyrolactones. Chem. Soc. Rev. 2018, 47, 1773–1782. [Google Scholar] [CrossRef] [PubMed]
  12. Kitson, R.R.A.; Millemaggi, A.; Taylor, R.J.K. The renaissance of α-methylene-γ-butyrolactones: New synthetic approaches. Angew. Chem. Int. Ed. 2009, 48, 9426–9451. [Google Scholar] [CrossRef] [PubMed]
  13. Mao, B.; Fañanás-Mastral, M.; Feringa, B.L. Catalytic asymmetric synthesis of butenolides and butyrolactones. Chem. Rev. 2017, 117, 10502–10566. [Google Scholar] [CrossRef]
  14. Seitz, M.; Reiser, O. Synthetic approaches towards structurally diverse γ-butyrolactone natural-product-like compounds. Curr. Opin. Chem. Biol. 2005, 9, 285–292. [Google Scholar] [CrossRef] [PubMed]
  15. Vivino, F.; Al-Hashimi, I.; Khan, Z. Pilocarpine Tablets for the Treatment of Dry Mouth and Dry Eye Symptoms in Patients With Sjogren Syndrome. Arch. Intern. Med. 1999, 159, 174–181. [Google Scholar] [CrossRef]
  16. Kagawa, C.M.; Cella, J.A.; Van Arman, C.G. Action of New Steroids in Blocking Effects of Aldosterone and Deoxycorticosterone on Salt. Science 1957, 126, 1015–1016. [Google Scholar] [CrossRef]
  17. Struthers, A.; Krum, H.; Williams, G.H. A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin. Cardiol. 2008, 31, 153–158. [Google Scholar] [CrossRef] [PubMed]
  18. Krattenmacher, R. Drospirenone: Pharmacology and pharmacokinetics of a unique progestogen. Contraception 2000, 62, 29–38. [Google Scholar] [CrossRef]
  19. Xu, H.; Lv, M.; Tian, X. A Review on Hemisynthesis, Biosynthesis, Biological Activities, Mode of Action, and Structure-Activity Relationship of Podophyllotoxins: 2003–2007. Curr. Med. Chem. 2009, 16, 327–349. [Google Scholar] [CrossRef]
  20. Yang, J.; Bogni, A.; Schuetz, E.G.; Ratain, M.; Eileen Dolan, M.; McLeod, H.; Gong, L.; Thorn, C.; Relling, M.V.; Klein, T.E.; et al. Etoposide pathway. Pharm. Genom. 2009, 19, 552–553. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  21. Clark, P.I.; Slevin, M.L. The Clinical Pharmacology of Etoposide and Teniposide. Clin. Pharm. 1987, 12, 223–252. [Google Scholar] [CrossRef] [PubMed]
  22. Tantry, U.S.; Liu, F.; Chen, G.; Gurbel, P.A. Vorapaxar in the secondary prevention of atherothrombosis. Expert Rev. Cardiovasc. Ther. 2015, 13, 1293–1305. [Google Scholar] [CrossRef] [PubMed]
  23. Chen, H.; Wu, G.; Gao, S.; Guo, R.; Zhao, Z.; Yuan, H.; Liu, S.; Wu, J.; Lu, X.; Yuan, X.; et al. Discovery of Potent Small-Molecule Inhibitors of Ubiquitin-Conjugating Enzyme UbcH5c from α-Santonin Derivatives. J. Med. Chem. 2017, 60, 6828–6852. [Google Scholar] [CrossRef] [PubMed]
  24. Sun, Q.; Zhang, W. Tetrahydronaphtho[1,2-b]furan-2(3H)-One Derivatives and Their Preparation, Pharmaceutical Compositions and Use in the Treatment of Rheumatoid Arthritis. WO2019011285, 17 January 2019. [Google Scholar]
  25. Chen, L.Z.; Wu, J.; Li, K.; Wu, Q.Q.; Chen, R.; Liu, X.H.; Ruan, B.F. Novel phthalide derivatives: Synthesis and anti-inflammatory activity in vitro and in vivo. Eur. J. Med. Chem. 2020, 206, 112722. [Google Scholar] [CrossRef] [PubMed]
  26. Ruan, B.; Li, Y. Resveratrol-Phthalide Hybrid Compound for Anti-Inflammatory Research and Its Preparation Method. CN110105316, 9 August 2019. [Google Scholar]
  27. Tran, Q.T.N.; Wong, W.S.F.; Chai, C.L.L. The identification of naturally occurring labdane diterpenoid calcaratarin D as a potential anti-inflammatory agent. Eur. J. Med. Chem. 2019, 174, 33–44. [Google Scholar] [CrossRef]
  28. Siedle, B.; García-Piñeres, A.J.; Murillo, R.; Schulte-Mönting, J.; Castro, V.; Rüngeler, P.; Klaas, C.A.; Da Costa, F.B.; Kisiel, W.; Merfort, I. Quantitative structure-activity relationship of sesquiterpene lactones as inhibitors of the transcription factor NF-κB. J. Med. Chem. 2004, 47, 6042–6054. [Google Scholar] [CrossRef]
  29. Nicolaou, K.C.; Sanchini, S.; Sarlah, D.; Lu, G.; Wu, T.R.; Nomura, D.K.; Cravatt, B.F.; Cubitt, B.; De La Torre, J.C.; Hessell, A.J.; et al. Design, synthesis, and biological evaluation of a biyouyanagin compound library. Proc. Natl. Acad. Sci. USA 2011, 108, 6715–6720. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  30. Yang, Y.N.; Huang, X.Y.; Feng, Z.M.; Jiang, J.S.; Zhang, P.C. New Butyrolactone Type Lignans from Arctii Fructus and Their Anti-inflammatory Activities. J. Agric. Food Chem. 2015, 63, 7958–7966. [Google Scholar] [CrossRef] [PubMed]
  31. Singh, P.; Mittal, A.; Bhardwaj, A.; Kaur, S.; Kumar, S. 1-Toluene-sulfonyl-3-[(3′-hydroxy-5′-substituted)-γ-butyrolactone]-indoles: Synthesis, COX-2 inhibition and anti-cancer activities. Bioorganic Med. Chem. Lett. 2008, 18, 85–89. [Google Scholar] [CrossRef]
  32. Brethon, A.; Chantalat, L.; Christin, O.; Clary, L.; Fournier, J.F.; Gastreich, M.; Harris, C.S.; Isabet, T.; Pascau, J.; Thoreau, E.; et al. New Caspase-1 inhibitor by scaffold hopping into bio-inspired 3D-fragment space. Bioorganic Med. Chem. Lett. 2017, 27, 5373–5377. [Google Scholar] [CrossRef] [PubMed]
  33. Tanaka, K.; Itazaki, H.; Yoshida, T. Cinatrins, a novel family of phospholipase a2 inhibitors: II. Biological activities. J. Antibiot. 1992, 45, 50–55. [Google Scholar] [CrossRef] [PubMed]
  34. Brisdelli, F.; Perilli, M.; Sellitri, D.; Piovano, M.; Garbarino, J.A.; Nicoletti, M.; Bozzi, A.; Amicosante, G.; Celenza, G. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: An in vitro study. Phyther. Res. 2013, 27, 431–437. [Google Scholar] [CrossRef] [PubMed]
  35. Roy, P.K.; Roy, S.; Ueda, K. New cytotoxic cembranolides from an Okinawan soft coral, Lobophytum sp. Fitoterapia 2019, 136, 104162. [Google Scholar] [CrossRef] [PubMed]
  36. Salaski, E.J.; Krishnamurthy, G.; Ding, W.D.; Yu, K.; Insaf, S.S.; Eid, C.; Shim, J.; Levin, J.I.; Tabei, K.; Toral-Barza, L.; et al. Pyranonaphthoquinone lactones: A new class of AKT selective kinase inhibitors alkylate a regulatory loop cysteine. J. Med. Chem. 2009, 52, 2181–2184. [Google Scholar] [CrossRef] [PubMed]
  37. Takano, S.; Hasuda, K.; Ito, A.; Koide, Y.; Ishii, F.; Haneda, I.; Chihara, S.; Koyama, Y. A new antibiotic, medermycin. J. Antibiot. 1976, 29, 765–768. [Google Scholar] [CrossRef] [Green Version]
  38. Bergy, M.E. Kalafungin, a new broade spectrum antibiotic. J. Antibiot. 1968, 21, 454–457. [Google Scholar] [CrossRef] [Green Version]
  39. Iwai, Y.; Kōra, A.; Takahashi, Y.; Hayashi, T.; Awaya, J.; Masuma, R.; Ōiwa, R.; Ōmura, S. Production of deoxyfrenolicin and a new antibiotic, frenolicin B by streptomyces roseofulvus strain AM-3867. J. Antibiot. 1978, 31, 959–965. [Google Scholar] [CrossRef] [Green Version]
  40. Lee, K.-H.; Rice, G.K.; Hall, I.H.; Amarnath, V. Antitumor agents. 86. Synthesis and cytotoxicity of .alpha.-methylene-.gamma.-lactone-bearing purines. J. Med. Chem. 1987, 30, 586–588. [Google Scholar] [CrossRef] [PubMed]
  41. Huth, J.R.; Park, C.; Petros, A.M.; Kunzer, A.R.; Wendt, M.D.; Wang, X.; Lynch, C.L.; Mack, J.C.; Swift, K.M.; Judge, R.A.; et al. Discovery and Design of Novel HSP90 Inhibitors Using Multiple Fragment-based Design Strategies. Chem. Biol. Drug Des. 2007, 70, 1–12. [Google Scholar] [CrossRef] [PubMed]
  42. Nozaki, Y.; Katayama, N.; Harada, S.; Ono, H.; Okazaki, H. Lactivicin, a naturally occurring non-β-lactam antibiotic having β-lactam-like action: Biological activities and mode of action. J. Antibiot. 1989, 42, 84–93. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Nozaki, Y.; Katayama, N.; Ono, H.; Tsubotani, S.; Harada, S.; Okazaki, H.; Nakao, Y. Binding of a non-β-lactam antibiotic to penicillin-binding proteins. Nature 1987, 325, 179–180. [Google Scholar] [CrossRef] [PubMed]
  44. Gal, Z.; Koncz, A.; Szabo, I.; Deak, E.; Benko, I.; Barabas, G.; Hernandi, F.; Kovacs, P. A synthetic γ-lactone group with β-lactamase inhibitory and sporulation initiation effects. J. Chemother. 2000, 12, 274–279. [Google Scholar] [CrossRef]
  45. Pavlović, D.; Mutak, S.; Andreotti, D.; Biondi, S.; Cardullo, F.; Paio, A.; Piga, E.; Donati, D.; Lociuro, S. Synthesis and structure-activity relationships of α-amino-γ-lactone ketolides: A novel class of macrolide antibiotics. ACS Med. Chem. Lett. 2014, 5, 1133–1137. [Google Scholar] [CrossRef] [Green Version]
  46. Kochikyan, T.V.; Arutyunyan, E.V.; Samvelyan, M.A.; Arutyunyan, V.S.; Avetisyan, A.A.; Paronikyan, R.V.; Stepanyan, G.M. Synthesis and antibacterial properties of hydrazonothiazolyl derivatives of saturated 2,4,4-substituted butanolides. Pharm. Chem. J. 2009, 43, 144–147. [Google Scholar] [CrossRef]
  47. Mazur, M.; Gładkowski, W.; Podkowik, M.; Bania, J.; Nawrot, J.; Białońska, A.; Wawrzeńczyk, C. Lactones 43. New biologically active lactones: β-cyclocitral derivatives. Pest Manag. Sci. 2014, 70, 286–294. [Google Scholar] [CrossRef]
  48. Hamann, H.J.; Abutaleb, N.S.; Pal, R.; Seleem, M.N.; Ramachandran, P.V. β,γ-Diaryl α-methylene-γ-butyrolactones as potent antibacterials against methicillin-resistant Staphylococcus aureus. Bioorg. Chem. 2020, 104, 104183. [Google Scholar] [CrossRef] [PubMed]
  49. Gładkowski, W.; Skrobiszewski, A.; Mazur, M.; Siepka, M.; Pawlak, A.; Obmińska-Mrukowicz, B.; Białońska, A.; Poradowski, D.; Drynda, A.; Urbaniak, M. Synthesis and anticancer activity of novel halolactones with β-aryl substituents from simple aromatic aldehydes. Tetrahedron 2013, 69, 10414–10423. [Google Scholar] [CrossRef]
  50. Włoch, A.; Stygar, D.; Bahri, F.; Bażanów, B.; Kuropka, P.; Chełmecka, E.; Pruchnik, H.; Gładkowski, W. Antiproliferative, antimicrobial and antiviral activity of β-aryl-δ-iodo-γ-lactones, their effect on cellular oxidative stress markers and biological membranes. Biomolecules 2020, 10, 1594. [Google Scholar] [CrossRef] [PubMed]
  51. Feng, J.T.; Ma, Z.Q.; Li, J.H.; He, J.; Xu, H.; Zhang, X. Synthesis and antifungal activity of carabrone derivatives. Molecules 2010, 15, 6485–6492. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  52. Jun-Tao, F.; De-Long, W.; Yong-Ling, W.; He, Y.; Xing, Z. New antifungal scaffold derived from a natural pharmacophore: Synthesis of α-methylene-γ-butyrolactone derivatives and their antifungal activity against Colletotrichum lagenarium. Bioorganic Med. Chem. Lett. 2013, 23, 4393–4397. [Google Scholar] [CrossRef]
  53. Wu, Y.; Wang, D.; Gao, Y.; Feng, J.; Zhang, X. New α-methylene-γ-butyrolactone derivatives as potential fungicidal agents: Design, synthesis and antifungal activities. Molecules 2016, 21, 130. [Google Scholar] [CrossRef] [Green Version]
  54. Björn Bode, H.; Irschik, H.; Wenzel, S.C.; Reichenbach, H.; Müller, R.; Höfle, G. The leupyrrins: A structurally unique family of secondary metabolites from the myxobacterium Sorangium cellulosum. J. Nat. Prod. 2003, 66, 1203–1206. [Google Scholar] [CrossRef]
  55. Herkommer, D.; Thiede, S.; Wosniok, P.R.; Dreisigacker, S.; Tian, M.; Debnar, T.; Irschik, H.; Menche, D. Stereochemical determination of the leupyrrins and total synthesis of leupyrrin A1. J. Am. Chem. Soc. 2015, 137, 4086–4089. [Google Scholar] [CrossRef] [PubMed]
  56. Wosniok, P.R.; Knopf, C.; Dreisigacker, S.; Orozco-Rodriguez, J.M.; Hinkelmann, B.; Mueller, P.P.; Brönstrup, M.; Menche, D. SAR Studies of the Leupyrrins: Design and Total Synthesis of Highly Potent Simplified Leupylogs. Chem. A Eur. J. 2020, 26, 15074–15078. [Google Scholar] [CrossRef]
  57. Yang, N.; Wang, Q.-H.; Wang, W.-Q.; Wang, J.; Li, F.; Tan, S.-P.; Cheng, M.-S. The design, synthesis and in vitro immunosuppressive evaluation of novel isobenzofuran derivatives. Bioorg. Med. Chem. Lett. 2012, 22, 53–56. [Google Scholar] [CrossRef]
  58. Reinhardt, J.K.; Klemd, A.M.; Danton, O.; De Mieri, M.; Smieško, M.; Huber, R.; Bürgi, T.; Gründemann, C.; Hamburger, M. Sesquiterpene Lactones from Artemisia argyi: Absolute Configuration and Immunosuppressant Activity. J. Nat. Prod. 2019, 82, 1424–1433. [Google Scholar] [CrossRef] [PubMed]
  59. Chinthakindi, P.K.; Singh, J.; Gupta, S.; Nargotra, A.; Mahajan, P.; Kaul, A.; Ahmed, Z.; Koul, S.; Sangwan, P.L. Synthesis of α-santonin derivatives for diminutive effect on T and B-cell proliferation and their structure activity relationships. Eur. J. Med. Chem. 2017, 127, 1047–1058. [Google Scholar] [CrossRef]
  60. Xiang, M.; Liu, T.; Tan, W.; Ren, H.; Li, H.; Liu, J.; Cao, H.; Cheng, Q.; Liu, X.; Zhu, H.; et al. Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells/CD8 + T cells communication in mice. Hepatology 2016, 64, 2135–2150. [Google Scholar] [CrossRef]
  61. Zhang, Y.; Xiang, M. Kinsenoside Having Good Therapeutic Effect on Autoimmune Hepatitis (AIH), and Its Application and Preparation Method. CN106317142, 11 January 2017. [Google Scholar]
  62. Liu, X.; Fu, J.; Yao, X.J.; Yang, J.; Liu, L.; Xie, T.G.; Jiang, P.C.; Jiang, Z.H.; Zhu, G.Y. Phenolic Constituents Isolated from the Twigs of Cinnamomum cassia and Their Potential Neuroprotective Effects. J. Nat. Prod. 2018, 81, 1333–1342. [Google Scholar] [CrossRef]
  63. Wang, S.; Jin, D.Q.; Xie, C.; Wang, H.; Wang, M.; Xu, J.; Guo, Y. Isolation, characterization, and neuroprotective activities of sesquiterpenes from Petasites japonicus. Food Chem. 2013, 141, 2075–2082. [Google Scholar] [CrossRef] [PubMed]
  64. Yang, S.; Wang, S.; Peng, N.; Xie, Z.; Wang, P.; Zhao, C.; Wei, L.; Yang, H.; Zhao, B.; Miao, J.; et al. Butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran- 2(3H)-one protects against amyloid-β peptides-induced cytotoxicity in PC12 cells. J. Alzheimer’s Dis. 2012, 28, 345–356. [Google Scholar] [CrossRef]
  65. Wei, L.; Yang, H.; Xie, Z.; Yang, S.; Yang, H.; Zhao, C.; Wang, P.; Xu, S.; Miao, J.; Zhao, B.; et al. A Butyrolactone Derivative 3BDO Alleviates Memory Deficits and Reduces Amyloid-β Deposition in an AβPP/PS1 Transgenic Mouse Model. J. Alzheimer’s Dis. 2012, 30, 531–543. [Google Scholar] [CrossRef]
  66. Min, B.S.; Na, M.K.; Oh, S.R.; Ahn, K.S.; Jeong, G.S.; Li, G.; Lee, S.K.; Joung, H.; Lee, H.K. New furofuran and butyrolactone lignans with antioxidant activity from the stem bark of Styrax japonica. J. Nat. Prod. 2004, 67, 1980–1984. [Google Scholar] [CrossRef]
  67. Lohezic-Le Devehat, F.; Tomasi, S.; Elix, J.A.; Bernard, A.; Rouaud, I.; Uriac, P.; Boustie, J. Stictic acid derivatives from the lichen Usnea articulata and their antioxidant activities. J. Nat. Prod. 2007, 70, 1218–1220. [Google Scholar] [CrossRef] [PubMed]
  68. Wu, W.; Liu, L.; Zhu, H.; Sun, Y.; Wu, Y.; Liao, H.; Gui, Y.; Li, L.; Liu, L.; Sun, F.; et al. Butyrolactone-I, an efficient α-glucosidase inhibitor, improves type 2 diabetes with potent TNF-α–lowering properties through modulating gut microbiota in db/db mice. FASEB J. 2019, 33, 12616–12629. [Google Scholar] [CrossRef] [Green Version]
  69. Trécant, C.; Dlubala, A.; George, P.; Pichat, P.; Ripoche, I.; Troin, Y. Synthesis and biological evaluation of analogues of M6G. Eur. J. Med. Chem. 2011, 46, 4035–4041. [Google Scholar] [CrossRef] [PubMed]
  70. Prévost, C. Iodo-Silver Benzoate and Its Use in the Oxidation of Ethylene Derivatives into α-Glycols. Compt. Rend 1933, 196, 1129–1131. [Google Scholar]
  71. Woodward, R.B.; Brutcher, F.V., Jr. cis-Hydroxylation of a synthetic steroid intermediate with iodine, silver acetate and wet acetic acid. J. Am. Chem. Soc. 1958, 80, 209–211. [Google Scholar] [CrossRef]
  72. Jacobsen, E.N.; Marko, I.; Mungall, W.S.; Schroeder, G.; Sharpless, K.B. Asymmetric dihydroxylation via ligand-accelerated catalysis. J. Am. Chem. Soc. 1988, 110, 1968–1970. [Google Scholar] [CrossRef]
  73. Kang, Y.-B.; Gade, L.H. Triflic Acid Catalyzed Oxidative Lactonization and Diacetoxylation of Alkenes Using Peroxyacids as Oxidants. J. Org. Chem. 2012, 77, 1610–1615. [Google Scholar] [CrossRef]
  74. Rosatella, A.A.; Afonso, C.A.M. Brønsted Acid-Catalyzed Dihydroxylation of Olefins in Aqueous Medium. Adv. Synth. Catal. 2011, 353, 2920–2926. [Google Scholar] [CrossRef]
  75. Kang, Y.-B.; Chen, X.-M.; Yao, C.-Z.; Ning, X.-S. Direct oxidative lactonization of alkenoic acids mediated solely by NaIO4: Beyond a simple oxidant. Chem. Commun. 2016, 52, 6193–6196. [Google Scholar] [CrossRef]
  76. Triandafillidi, I.; Raftopoulou, M.; Savvidou, A.; Kokotos, C.G. Organocatalytic Synthesis of Lactones by the Oxidation of Alkenoic Acids. ChemCatChem 2017, 9, 4120–4124. [Google Scholar] [CrossRef]
  77. Dagenais, R.; Lussier, T.; Legault, C.Y. Iodine(III)-Mediated Contraction of 3,4-Dihydropyranones: Access to Polysubstituted γ-Butyrolactones. Org. Lett. 2019, 21, 5290–5294. [Google Scholar] [CrossRef]
  78. Karila, D.; Leman, L.; Dodd, R.H. Copper-Catalyzed Iminoiodane-Mediated Aminolactonization of Olefins: Application to the Synthesis of 5,5-Disubstituted Butyrolactones. Org. Lett. 2011, 13, 5830–5833. [Google Scholar] [CrossRef]
  79. Evans, D.A.; Woerpel, K.A.; Hinman, M.M.; Faul, M.M. Bis(oxazolines) as chiral ligands in metal-catalyzed asymmetric reactions. Catalytic, asymmetric cyclopropanation of olefins. J. Am. Chem. Soc. 1991, 113, 726–728. [Google Scholar] [CrossRef]
  80. Evans, D.A.; Bilodeau, M.T.; Faul, M.M. Development of the Copper-Catalyzed Olefin Aziridination Reaction. J. Am. Chem. Soc. 1994, 116, 2742–2753. [Google Scholar] [CrossRef]
  81. Tamaru, Y.; Mizutani, M.; Furukawa, Y.; Kawamura, S.; Yoshida, Z.; Yanagi, K.; Minobe, M. 1,3-Asymmetric induction: Highly stereoselective synthesis of 2,4-trans-disubstituted γ-butyrolactones and γ-butyrothiolactones. J. Am. Chem. Soc. 1984, 106, 1079–1085. [Google Scholar] [CrossRef]
  82. Evans, D.A.; Ennis, M.D.; Mathre, D.J. Asymmetric alkylation reactions of chiral imide enolates. A practical approach to the enantioselective synthesis of α-substituted carboxylic acid derivatives. J. Am. Chem. Soc. 1982, 104, 1737–1739. [Google Scholar] [CrossRef]
  83. Moriyama, K.; Izumisawa, Y.; Togo, H. Oxidative Intramolecular Bromo-Amination of N-Alkenyl Sulfonamides via Umpolung of Alkali Metal Bromides. J. Org. Chem. 2011, 76, 7249–7255. [Google Scholar] [CrossRef]
  84. Moriyama, K.; Sugiue, T.; Nishinohara, C.; Togo, H. Divergent Synthesis of α,γ-Disubstituted γ-Butyrolactones through Diastereoselective Bromolactonization with Alkali Metal Bromide: Asymmetric Total Synthesis of (+)-Dubiusamine C. J. Org. Chem. 2015, 80, 9132–9140. [Google Scholar] [CrossRef] [PubMed]
  85. Balkrishna, S.J.; Prasad, C.D.; Panini, P.; Detty, M.R.; Chopra, D.; Kumar, S. Isoselenazolones as Catalysts for the Activation of Bromine: Bromolactonization of Alkenoic Acids and Oxidation of Alcohols. J. Org. Chem. 2012, 77, 9541–9552. [Google Scholar] [CrossRef]
  86. Detty, M.R.; Friedman, A.E.; McMillan, M. A Stepwise Mechanism for Oxidative Addition of Bromine to Organoselenium(II) and Organotellurium(II) Compounds. Organometallics 1994, 13, 3338–3345. [Google Scholar] [CrossRef]
  87. Rosocha, G.; Batey, R.A. Synthesis of 2-bromo-1-aryl-1H-indenes via a Ag(I) promoted domino 2π-electrocyclic ring-opening/4π-electrocyclization reaction of 1,2-diaryl substituted gem-dibromocyclopropanes. Tetrahedron 2013, 69, 8758–8768. [Google Scholar] [CrossRef]
  88. Kalmode, H.P.; Handore, K.L.; Reddy, D.S. Access to Fused Tricyclic γ-Butyrolactones, A Natural Product-like Scaffold. J. Org. Chem. 2017, 82, 7614–7620. [Google Scholar] [CrossRef]
  89. Kim, S.J.; Lough, A.J.; Batey, R.A. An Approach to the 9-Oxo-10-oxabicyclo[5.3.0]dec-2-ene Core of the Guaianolide and Pseudoguaianolide Sesquiterpenes via a Domino Electrocyclic Ring-Opening/Carboxylic Acid Trapping of a gem-Dibromocyclopropane. J. Org. Chem. 2018, 83, 13799–13810. [Google Scholar] [CrossRef]
  90. Bandini, M.; Eichholzer, A. Enantioselective Gold-Catalyzed Allylic Alkylation of Indoles with Alcohols: An Efficient Route to Functionalized Tetrahydrocarbazoles. Angew. Chem. Int. Ed. 2009, 48, 9533–9537. [Google Scholar] [CrossRef]
  91. Bandini, M.; Eichholzer, A.; Gualandi, A.; Quinto, T.; Savoia, D. Creating Chemical Diversity in Indole Compounds by Merging Au and Ru Catalysis. ChemCatChem 2010, 2, 661–665. [Google Scholar] [CrossRef]
  92. Marion, N.; Gealageas, R.; Nolan, S.P. [(NHC)AuI]-Catalyzed Rearrangement of Allylic Acetates. Org. Lett. 2007, 9, 2653–2656. [Google Scholar] [CrossRef] [PubMed]
  93. Wang, Y.-H.; Zhu, L.-L.; Zhang, Y.-X.; Chen, Z. Diastereoselective γ-vinyl butyrolactone synthesis via gold catalyzed cyclization of allylic acetate. Chem. Commun. 2010, 46, 577–579. [Google Scholar] [CrossRef] [PubMed]
  94. Chiarucci, M.; Locritani, M.; Cera, G.; Bandini, M. Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols. Beilstein J. Org. Chem. 2011, 7, 1198–1204. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  95. Liu, J.; Miotto, R.J.; Segard, J.; Erb, A.M.; Aponick, A. Catalytic Dehydrative Lactonization of Allylic Alcohols. Org. Lett. 2018, 20, 3034–3038. [Google Scholar] [CrossRef]
  96. Okada, T.; Sakaguchi, K.; Shinada, T.; Ohfune, Y. Au-catalyzed cyclization of allenylsilanes. Regioselective conversion to 2-amino-4-silylmethylene γ-butyrolactone. Tetrahedron Lett. 2011, 52, 5740–5743. [Google Scholar] [CrossRef]
  97. Guo, W.; Cheng, H.-G.; Chen, L.-Y.; Xuan, J.; Feng, Z.-J.; Chen, J.-R.; Lu, L.-Q.; Xiao, W.-J. De Novo Synthesis of γ,γ-Disubstituted Butyrolactones through a Visible Light Photocatalytic Arylation–Lactonization Sequence. Adv. Synth. Catal. 2014, 356, 2787–2793. [Google Scholar] [CrossRef]
  98. Yasu, Y.; Arai, Y.; Tomita, R.; Koike, T.; Akita, M. Highly Regio- and Diastereoselective Synthesis of CF3-Substituted Lactones via Photoredox-Catalyzed Carbolactonization of Alkenoic Acids. Org. Lett. 2014, 16, 780–783. [Google Scholar] [CrossRef]
  99. Sha, W.; Ni, S.; Han, J.; Pan, Y. Access to Alkyl-Substituted Lactone via Photoredox-Catalyzed Alkylation/Lactonization of Unsaturated Carboxylic Acids. Org. Lett. 2017, 19, 5900–5903. [Google Scholar] [CrossRef] [PubMed]
  100. Wei, X.-J.; Yang, D.-T.; Wang, L.; Song, T.; Wu, L.-Z.; Liu, Q. A Novel Intermolecular Synthesis of γ-Lactones via Visible-Light Photoredox Catalysis. Org. Lett. 2013, 15, 6054–6057. [Google Scholar] [CrossRef]
  101. Montgomery, T.P.; Hassan, A.; Park, B.Y.; Krische, M.J. Enantioselective conversion of primary alcohols to α-exo-methylene γ-butyrolactones via iridium-catalyzed C-C bond-forming transfer hydrogenation: 2-(Alkoxycarbonyl)allylation. J. Am. Chem. Soc. 2012, 134, 11100–11103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  102. Spielmann, K.; Niel, G.; De Figueiredo, R.M.; Campagne, J.M. Catalytic nucleophilic “umpoled” π-allyl reagents. Chem. Soc. Rev. 2018, 47, 1159–1173. [Google Scholar] [CrossRef] [PubMed]
  103. Leung, J.C.; Geary, L.M.; Chen, T.Y.; Zbieg, J.R.; Krische, M.J. Direct, redox-neutral prenylation and geranylation of secondary carbinol C-H bonds: C4-regioselectivity in ruthenium-catalyzed C-C couplings of dienes to α-hydroxy esters. J. Am. Chem. Soc. 2012, 134, 15700–15703. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  104. McInturff, E.L.; Mowat, J.; Waldeck, A.R.; Krische, M.J. Ruthenium-catalyzed hydrohydroxyalkylation of acrylates with diols and α-hydroxycarbonyl compounds to form spiro- and α-methylene-γ- butyrolactones. J. Am. Chem. Soc. 2013, 135, 17230–17235. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  105. Chen, W.; Yang, Q.; Zhou, T.; Tian, Q.; Zhang, G. Enantioselective Synthesis of α-exo-Methylene γ-Butyrolactones via Chromium Catalysis. Org. Lett. 2015, 17, 5236–5239. [Google Scholar] [CrossRef]
  106. McManus, H.A.; Guiry, P.J. Coupling of Bulky, Electron-Deficient Partners in Aryl Amination in the Preparation of Tridentate Bis(oxazoline) Ligands for Asymmetric Catalysis. J. Org. Chem. 2002, 67, 8566–8573. [Google Scholar] [CrossRef]
  107. Murata, Y.; Takahashi, M.; Yagishita, F.; Sakamoto, M.; Sengoku, T.; Yoda, H. Construction of Spiro-Fused 2-Oxindole/α-Methylene-γ-Butyrolactone Systems with Extremely High Enantioselectivity via Indium-Catalyzed Amide Allylation of N-Methyl Isatin. Org. Lett. 2013, 15, 6182–6185. [Google Scholar] [CrossRef] [PubMed]
  108. Hoffmann, H.M.R.; Rabe, J. Synthesis and Biological Activity of α-Methylene-γ-butyrolactones. Angew. Chem. Int. Ed. 1985, 24, 94–110. [Google Scholar] [CrossRef]
  109. Takahashi, M.; Murata, Y.; Yagishita, F.; Sakamoto, M.; Sengoku, T.; Yoda, H. Catalytic enantioselective amide allylation of isatins and its application in the synthesis of 2-oxindole derivatives spiro-fused to the α-methylene-γ-butyrolactone functionality. Chem. Eur. J. 2014, 20, 11091–11100. [Google Scholar] [CrossRef]
  110. Nair, V.; Vellalath, S.; Babu, B.P. Recent advances in carbon–carbon bond-forming reactions involving homoenolates generated by NHC catalysis. Chem. Soc. Rev. 2008, 37, 2691. [Google Scholar] [CrossRef] [PubMed]
  111. Sun, L.H.; Shen, L.T.; Ye, S. Highly diastereo- and enantioselective NHC-catalyzed [3+2] annulation of enals and isatins. Chem. Commun. 2011, 47, 10136–10138. [Google Scholar] [CrossRef]
  112. Dugal-Tessier, J.; O’Bryan, E.A.; Schroeder, T.B.H.; Cohen, D.T.; Scheidt, K.A. An N-heterocyclic carbene/lewis acid strategy for the stereoselective synthesis of spirooxindole lactones. Angew. Chem. Int. Ed. 2012, 51, 4963–4967. [Google Scholar] [CrossRef] [Green Version]
  113. Jin, Z.; Jiang, K.; Fu, Z.; Torres, J.; Zheng, P.; Yang, S.; Song, B.-A.; Chi, Y.R. Nucleophilic β-Carbon Activation of Propionic Acid as a 3-Carbon Synthon by Carbene Organocatalysis. Chem. Eur. J. 2015, 21, 9360–9363. [Google Scholar] [CrossRef] [PubMed]
  114. Xie, Y.; Yu, C.; Li, T.; Tu, S.; Yao, C. An NHC-catalyzed in situ activation strategy to β-functionalize saturated carboxylic acid: An enantioselective formal [3+2] annulation for spirocyclic oxindolo-γ-butyrolactones. Chem. Eur. J. 2015, 21, 5355–5359. [Google Scholar] [CrossRef]
  115. Xu, J.; Yuan, S.; Miao, M.; Chen, Z. 1-Hydroxybenzotriazole-Assisted, N-Heterocyclic Carbene Catalyzed β-Functionalization of Saturated Carboxylic Esters: Access to Spirooxindole Lactones. J. Org. Chem. 2016, 81, 11454–11460. [Google Scholar] [CrossRef]
  116. Goodman, C.G.; Walker, M.M.; Johnson, J.S. Enantioconvergent synthesis of functionalized γ-butyrolactones via (3+2)-annulation. J. Am. Chem. Soc. 2015, 137, 122–125. [Google Scholar] [CrossRef] [Green Version]
  117. Shaw, M.H.; Twilton, J.; MacMillan, D.W.C. Photoredox Catalysis in Organic Chemistry. J. Org. Chem. 2016, 81, 6898–6926. [Google Scholar] [CrossRef] [PubMed]
  118. Jeffrey, J.L.; Terrett, J.A.; MacMillant, D.W.C. O-H hydrogen bonding promotes H-atom transfer from α C-H bonds for C-alkylation of alcohols. Science 2015, 349, 1532–1536. [Google Scholar] [CrossRef] [Green Version]
  119. Kaplaneris, N.; Bisticha, A.; Papadopoulos, G.N.; Limnios, D.; Kokotos, C.G. Photoorganocatalytic synthesis of lactones: Via a selective C-H activation-alkylation of alcohols. Green Chem. 2017, 19, 4451–4456. [Google Scholar] [CrossRef]
  120. Shono, T.; Ohmizu, H.; Kawakami, S.; Sugiyama, H. Electroreductive hydrocoupling of activated olefins with ketones or aldehydes in the presence of trimethylchlorosilane. Tetrahedron Lett. 1980, 21, 5029–5032. [Google Scholar] [CrossRef]
  121. Kise, N.; Hamada, Y.; Sakurai, T. Electroreductive coupling of optically active α,β-unsaturated carbonyl compounds with diaryl ketones: Asymmetric synthesis of 4,5,5-trisubstituted γ-butyrolactones. Org. Lett. 2014, 16, 3348–3351. [Google Scholar] [CrossRef] [PubMed]
  122. Cao, J.; Dong, S.; Jiang, D.; Zhu, P.; Zhang, H.; Li, R.; Li, Z.; Wang, X.; Tang, W.; Du, D. β-Functionalization of Indolin-2-one-Derived Aliphatic Acids for the Divergent Synthesis of Spirooxindole γ-Butyrolactones. J. Org. Chem. 2017, 82, 4186–4193. [Google Scholar] [CrossRef]
  123. Khopade, T.M.; Sonawane, A.D.; Arora, J.S.; Bhat, R.G. Direct Organocatalytic Multicomponent Synthesis of Enantiopure γ-Butyrolactones via Tandem Knoevenagel-Michael-Lactonization Sequence. Adv. Synth. Catal. 2017, 359, 3905–3910. [Google Scholar] [CrossRef]
  124. Hamid, M.H.S.A.; Slatford, P.A.; Williams, J.M.J. Borrowing Hydrogen in the Activation of Alcohols. Adv. Synth. Catal. 2007, 349, 1555–1575. [Google Scholar] [CrossRef]
  125. Kim, S.W.; Zhang, W.; Krische, M.J. Catalytic Enantioselective Carbonyl Allylation and Propargylation via Alcohol-Mediated Hydrogen Transfer: Merging the Chemistry of Grignard and Sabatier. Acc. Chem. Res. 2017, 50, 2371–2380. [Google Scholar] [CrossRef] [PubMed]
  126. Peña-López, M.; Neumann, H.; Beller, M. Ruthenium pincer-catalyzed synthesis of substituted γ-butyrolactones using hydrogen autotransfer methodology. Chem. Commun. 2015, 51, 13082–13085. [Google Scholar] [CrossRef]
  127. Keshavarz, M.; Ahmady, A.Z.; Mostoufi, A.; Mohtasham, N. One-pot green regioselesctive synthesis of γ-lactones from epoxides and ketene silyl acetals using 1,3-Dimethylimidazolium fluoride as a recoverable Metal-free catalyst. Molecules 2017, 22, 1385. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  128. Zeller, M.A.; Riener, M.; Nicewicz, D.A. Butyrolactone synthesis via polar radical crossover cycloaddition reactions: Diastereoselective syntheses of methylenolactocin and protolichesterinic acid. Org. Lett. 2014, 16, 4810–4813. [Google Scholar] [CrossRef] [PubMed]
  129. Cavanaugh, C.L.; Nicewicz, D.A. Synthesis of α-Benzyloxyamino-γ-butyrolactones via a Polar Radical Crossover Cycloaddition Reaction. Org. Lett. 2015, 17, 6082–6085. [Google Scholar] [CrossRef]
  130. Triandafillidi, I.; Kokotou, M.G.; Kokotos, C.G. Photocatalytic Synthesis of γ-Lactones from Alkenes: High-Resolution Mass Spectrometry as a Tool to Study Photoredox Reactions. Org. Lett. 2018, 20, 36–39. [Google Scholar] [CrossRef] [PubMed]
  131. Yousuf, S.K.; Mukherjee, D.; L, M.; Taneja, S.C. Highly regio-and stereoselective one-pot synthesis of carbohydrate-based butyrolactones. Org. Lett. 2011, 13, 576–579. [Google Scholar] [CrossRef]
  132. Ye, Z.; Cai, X.; Li, J.; Dai, M. Catalytic Cyclopropanol Ring Opening for Divergent Syntheses of γ-Butyrolactones and δ-Ketoesters Containing All-Carbon Quaternary Centers. ACS Catal. 2018, 8, 5907–5914. [Google Scholar] [CrossRef]
  133. Grandjean, J.M.M.; Nicewicz, D.A. Synthesis of highly substituted tetrahydrofurans by catalytic polar-radical-crossover cycloadditions of alkenes and alkenols. Angew. Chem. Int. Ed. 2013, 52, 3967–3971. [Google Scholar] [CrossRef]
  134. Gesmundo, N.J.; Grandjean, J.M.M.; Nicewicz, D.A. Amide and amine nucleophiles in polar radical crossover cycloadditions: Synthesis of γ-lactams and pyrrolidines. Org. Lett. 2015, 17, 1316–1319. [Google Scholar] [CrossRef] [PubMed]
  135. Wu, X.F.; Fang, X.; Wu, L.; Jackstell, R.; Neumann, H.; Beller, M. Transition-metal-catalyzed carbonylation reactions of olefins and alkynes: A personal account. Acc. Chem. Res. 2014, 47, 1041–1053. [Google Scholar] [CrossRef] [PubMed]
  136. Babjak, M.; Markovič, M.; Kandríková, B.; Gracza, T. Homogeneous cyclocarbonylation of alkenols with iron pentacarbonyl. Synth. 2014, 46, 809–816. [Google Scholar] [CrossRef]
  137. Lopatka, P.; Markovič, M.; Koóš, P.; Ley, S.V.; Gracza, T. Continuous Pd-Catalyzed Carbonylative Cyclization Using Iron Pentacarbonyl as a CO Source. J. Org. Chem. 2019, 84, 14394–14406. [Google Scholar] [CrossRef]
  138. Li, J.; Yang, S.; Wu, W.; Jiang, H. Novel palladium-catalyzed cascade carboxylative annulation to construct functionalized γ-lactones in ionic liquids. Chem. Commun. 2014, 50, 1381–1383. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  139. Yang, S.-R.; Jiang, H.-F.; Li, Y.-Q.; Chen, H.-J.; Luo, W.; Xu, Y.-B. Protonolysis of the carbon–palladium bond in palladium(II)-catalyzed enyne cyclization in imidazolium-type ionic liquids. Tetrahedron 2008, 64, 2930–2937. [Google Scholar] [CrossRef]
  140. Higashimae, S.; Tamai, T.; Nomoto, A.; Ogawa, A. Selective Thiolative Lactonization of Internal Alkynes Bearing a Hydroxyl Group with Carbon Monoxide and Organic Disulfides Catalyzed by Transition-Metal Complexes. J. Org. Chem. 2015, 80, 7126–7133. [Google Scholar] [CrossRef] [PubMed]
  141. Rosa, D.; Nikolaev, A.; Nithiy, N.; Orellana, A. Palladium-Catalyzed Cross-Coupling Reactions of Cyclopropanols. Synlett 2015, 26, 441–448. [Google Scholar]
  142. Davis, D.C.; Walker, K.L.; Hu, C.; Zare, R.N.; Waymouth, R.M.; Dai, M. Catalytic Carbonylative Spirolactonization of Hydroxycyclopropanols. J. Am. Chem. Soc. 2016, 138, 10693–10699. [Google Scholar] [CrossRef] [Green Version]
  143. Breit, B. Synthetic aspects of stereoselective hydroformylation. Acc. Chem. Res. 2003, 36, 264–275. [Google Scholar] [CrossRef] [PubMed]
  144. Ueki, Y.; Ito, H.; Usui, I.; Breit, B. Formation of quaternary carbon centers by highly regioselective hydroformylation with catalytic amounts of a reversibly bound directing group. Chem. Eur. J. 2011, 17, 8555–8558. [Google Scholar] [CrossRef] [PubMed]
  145. Deng, Y.; Wang, H.; Sun, Y.; Wang, X. Principles and Applications of Enantioselective Hydroformylation of Terminal Disubstituted Alkenes. ACS Catal. 2015, 5, 6828–6837. [Google Scholar] [CrossRef]
  146. You, C.; Li, S.; Li, X.; Lv, H.; Zhang, X. Enantioselective Rh-Catalyzed Anti-Markovnikov Hydroformylation of 1,1-Disubstituted Allylic Alcohols and Amines: An Efficient Route to Chiral Lactones and Lactams. ACS Catal. 2019, 9, 8529–8533. [Google Scholar] [CrossRef]
  147. Li, S.; Ma, S. Highly selective nickel-catalyzed methyl-carboxylation of homopropargylic alcohols for α-alkylidene-γ;-butyrolactones. Org. Lett. 2011, 13, 6046–6049. [Google Scholar] [CrossRef] [PubMed]
  148. Li, S.; Ma, S. CO 2-activation for γ-butyrolactones and its application in the total synthesis of (±)-heteroplexisolide e. Chem. Asian J. 2012, 7, 2411–2418. [Google Scholar] [CrossRef]
  149. Lloyd, M.G.; Taylor, R.J.K.; Unsworth, W.P. A One-Pot C–H Insertion/Olefination Sequence for the Formation of α-Alkylidene-γ-butyrolactones. Org. Lett. 2014, 16, 2772–2775. [Google Scholar] [CrossRef] [PubMed]
  150. Lloyd, M.G.; D’Acunto, M.; Taylor, R.J.K.; Unsworth, W.P. α-Alkylidene-γ-butyrolactone synthesis via one-pot C–H insertion/olefination: Substrate scope and the total synthesis of (±)-cedarmycins A and B. Tetrahedron 2015, 71, 7107–7123. [Google Scholar] [CrossRef]
  151. Lloyd, M.G.; D’Acunto, M.; Taylor, R.J.K.; Unsworth, W.P. A selective C–H insertion/olefination protocol for the synthesis of α-methylene-γ-butyrolactone natural products. Org. Biomol. Chem. 2016, 14, 1641–1645. [Google Scholar] [CrossRef] [PubMed]
  152. Schwarz, W.; Schossig, J.; Rossbacher, R.; Pinkos, R.; Höke, H. Butyrolactone. In Ullmann’s Encyclopedia of Industrial Chemistry; Wiley: Weinheim, Germany, 2019; pp. 1–7. ISBN 9783527306732. [Google Scholar]
  153. Yim, H.; Haselbeck, R.; Niu, W.; Pujol-Baxley, C.; Burgard, A.; Boldt, J.; Khandurina, J.; Trawick, J.D.; Osterhout, R.E.; Stephen, R.; et al. Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat. Chem. Biol. 2011, 7, 445–452. [Google Scholar] [CrossRef] [PubMed]
  154. Hwang, D.W.; Kashinathan, P.; Lee, J.M.; Lee, J.H.; Lee, U.; Hwang, J.-S.; Hwang, Y.K.; Chang, J.-S. Production of γ-butyrolactone from biomass-derived 1,4-butanediol over novel copper-silica nanocomposite. Green Chem. 2011, 13, 1672. [Google Scholar] [CrossRef]
  155. Zhang, B.; Zhu, Y.; Ding, G.; Zheng, H.; Li, Y. Modification of the supported Cu/SiO2 catalyst by alkaline earth metals in the selective conversion of 1,4-butanediol to γ-butyrolactone. Appl. Catal. A Gen. 2012, 443–444, 191–201. [Google Scholar] [CrossRef]
  156. Reddy, K.H.P.; Anand, N.; Venkateswarlu, V.; Rao, K.S.R.; Burri, D.R. A selective synthesis of 1-phenylethanol and γ-butyrolactone through coupling processes over Cu/MgO catalysts. J. Mol. Catal. A Chem. 2012, 355, 180–185. [Google Scholar] [CrossRef]
  157. Hu, Q.; Fan, G.; Yang, L.; Cao, X.; Zhang, P.; Wang, B.; Li, F. A gas-phase coupling process for simultaneous production of γ-butyrolactone and furfuryl alcohol without external hydrogen over bifunctional base-metal heterogeneous catalysts. Green Chem. 2016, 18, 2317–2322. [Google Scholar] [CrossRef]
  158. Prasad, H.; Kannapu, R.; Suh, Y.W.; Narani, A. Coupling of 1,4-Butanediol Dehydrogenation with Nitrobenzene Hydrogenation for Simultaneous Synthesis of γ-Butyrolactone and Aniline over Promoted Cu-MgO Catalysts: Effect of Promoters. Catal. Lett. 2017, 147, 90–101. [Google Scholar]
  159. Hari, K.; Reddy, P.; Suh, Y.; Anand, N.; David, B.; Seetha, K.; Rao, R. Coupling of ortho-chloronitrobenzene hydrogenation with 1,4-butanediol dehydrogenation over Cu-MgO catalysts: A hydrogen free process. Catal. Commun. 2017, 95, 21–25. [Google Scholar]
  160. Nagaiah, P.; Venkat Rao, M.; Thirupathaiah, K.; Venkateshwarlu, V.; David Raju, B.; Rama Rao, K.S. Selective vapour phase dehydrogenation of biomass-derived 1,4-butanediol to gamma butyrolactone over Cu/ZrO2 catalysts: Influence of La2O3 promotor. Res. Chem. Intermed. 2018, 44, 5817–5831. [Google Scholar] [CrossRef]
  161. Bhanushali, J.T.; Prasad, D.; Patil, K.N.; Reddy, K.S.; Rama Rao, K.S.; Jadhav, A.H.; Nagaraja, B.M. Simultaneous dehydrogenation of 1,4- butanediol to γ-butyrolactone and hydrogenation of benzaldehyde to benzyl alcohol mediated over competent CeO2–Al2O3 supported Cu as catalyst. Int. J. Hydrogen Energy 2020, 45, 12874–12888. [Google Scholar] [CrossRef]
  162. Aellig, C.; Jenny, F.; Scholz, D.; Wolf, P.; Giovinazzo, I.; Kollhoff, F.; Hermans, I. Combined 1,4-butanediol lactonization and transfer hydrogenation/hydrogenolysis of furfural-derivatives under continuous flow conditions. Catal. Sci. Technol. 2014, 4, 2326–2331. [Google Scholar] [CrossRef]
  163. Huang, L.; Romero, E.; Ressmann, A.K.; Rudroff, F.; Hollmann, F.; Fraaije, M.W.; Kara, S. Nicotinamide Adenine Dinucleotide-Dependent Redox-Neutral Convergent Cascade for Lactonizations with Type II Flavin-Containing Monooxygenase. Adv. Synth. Catal. 2017, 359, 2142–2148. [Google Scholar] [CrossRef] [Green Version]
  164. Kara, S.; Spickermann, D.; Schrittwieser, J.H.; Weckbecker, A.; Leggewie, C.; Arends, I.W.C.E.; Hollmann, F. Access to Lactone Building Blocks via Horse Liver Alcohol Dehydrogenase-Catalyzed Oxidative Lactonization. ACS Catal. 2013, 3, 2436–2439. [Google Scholar] [CrossRef]
  165. Li, X.; Zheng, J.; Yang, X.; Dai, W.; Fan, K. Preparation and application of highly efficient Au/SnO2 catalyst in the oxidative lactonization of 1,4-butanediol to γ-butyrolactone. Chin. J. Catal. 2013, 34, 1013–1019. [Google Scholar] [CrossRef]
  166. Li, X.; Cui, Y.; Yang, X.; Dai, W.; Fan, K. Highly efficient and stable Au/Mn2O3 catalyst for oxidative cyclization of 1,4-butanediol to γ-butyrolactone. Appl. Catal. A Gen. 2013, 458, 63–70. [Google Scholar] [CrossRef]
  167. Xie, X.; Stahl, S.S. Efficient and Selective Cu/Nitroxyl-Catalyzed Methods for Aerobic Oxidative Lactonization of Diols. J. Am. Chem. Soc. 2015, 137, 3767–3770. [Google Scholar] [CrossRef]
  168. Chakraborty, S.; Lagaditis, P.O.; Förster, M.; Bielinski, E.A.; Hazari, N.; Holthausen, M.C.; Jones, W.D.; Schneider, S. Well-Defined Iron Catalysts for the Acceptorless Reversible Dehydrogenation-Hydrogenation of Alcohols and Ketones. ACS Catal. 2014, 4, 3994–4003. [Google Scholar] [CrossRef]
  169. Tang, Y.; Meador, R.I.L.; Malinchak, C.T.; Harrison, E.E.; McCaskey, K.A.; Hempel, M.C.; Funk, T.W. (Cyclopentadienone)iron-Catalyzed Transfer Dehydrogenation of Symmetrical and Unsymmetrical Diols to Lactones. J. Org. Chem. 2020, 85, 1823–1834. [Google Scholar] [CrossRef]
  170. Coleman, M.G.; Brown, A.N.; Bolton, B.A.; Guan, H. Iron-Catalyzed Oppenauer-Type Oxidation of Alcohols. Adv. Synth. Catal. 2010, 352, 967–970. [Google Scholar] [CrossRef]
  171. Peña-López, M.; Neumann, H.; Beller, M. Iron(II) Pincer-Catalyzed Synthesis of Lactones and Lactams through a Versatile Dehydrogenative Domino Sequence. ChemCatChem 2015, 7, 865–871. [Google Scholar] [CrossRef]
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Figure 1. Bond disconnections for the synthesis of γ-butyrolactones.
Figure 1. Bond disconnections for the synthesis of γ-butyrolactones.
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Figure 2. TfOH-catalyzed oxidative lactonization with peroxyacid.
Figure 2. TfOH-catalyzed oxidative lactonization with peroxyacid.
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Figure 3. TfOH-catalyzed oxidative lactonization with sodium periodate.
Figure 3. TfOH-catalyzed oxidative lactonization with sodium periodate.
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Figure 4. Trifluoroacetophenone-catalyzed oxidative lactonization with hydrogen peroxide.
Figure 4. Trifluoroacetophenone-catalyzed oxidative lactonization with hydrogen peroxide.
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Figure 5. Oxidative ring contraction of 3,4-dihydropyran-2-ones.
Figure 5. Oxidative ring contraction of 3,4-dihydropyran-2-ones.
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Figure 6. Aminolactonization of t-butyl pentenoate with iminoiodane (top) and the application of the resulting γ-butyrolactone (bottom).
Figure 6. Aminolactonization of t-butyl pentenoate with iminoiodane (top) and the application of the resulting γ-butyrolactone (bottom).
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Figure 7. Bromolactonization of pentenoic acid with KBr and Oxone.
Figure 7. Bromolactonization of pentenoic acid with KBr and Oxone.
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Figure 8. Bromolactonization of pentenoic acid with isoselenazolone.
Figure 8. Bromolactonization of pentenoic acid with isoselenazolone.
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Figure 9. Acid-promoted cyclopropane opening/intramolecular ester trapping.
Figure 9. Acid-promoted cyclopropane opening/intramolecular ester trapping.
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Figure 10. Silver-mediated cyclopropane opening/intramolecular acid trapping.
Figure 10. Silver-mediated cyclopropane opening/intramolecular acid trapping.
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Figure 11. Gold-catalyzed intramolecular allylic alkylation of allylic acetate.
Figure 11. Gold-catalyzed intramolecular allylic alkylation of allylic acetate.
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Figure 12. Gold-NHC complex catalyzed intramolecular allylic alkylation of allylic alcohol.
Figure 12. Gold-NHC complex catalyzed intramolecular allylic alkylation of allylic alcohol.
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Figure 13. Gold-catalyzed dehydrative lactonization.
Figure 13. Gold-catalyzed dehydrative lactonization.
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Figure 14. Gold-catalyzed lactonization of allene system.
Figure 14. Gold-catalyzed lactonization of allene system.
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Figure 15. Photoredox-catalyzed γ-butyrolactone synthesis.
Figure 15. Photoredox-catalyzed γ-butyrolactone synthesis.
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Figure 16. Asymmetric synthesis of α-exo-methylene-γ-butyrolactone via iridium-catalyzed 2-(alkoxycarbonyl)allylation.
Figure 16. Asymmetric synthesis of α-exo-methylene-γ-butyrolactone via iridium-catalyzed 2-(alkoxycarbonyl)allylation.
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Figure 17. Syntheses of γ-butyrolactones via ruthenium-catalyzed hydrohydroxyalkylation. (a) Syntheses of spiro-γ-butyrolactones from diols and methyl acrylate; (b) Syntheses of polysubstituted 2,3’-spirooxindole-γ-butyrolactones from N-benzyl-3-hydroxyoxindole and acrylic esters; (c) Syntheses of α-exo-methylene-γ-butyrolactones from hydroxyl-substituted methacrylate and diols; (d) Redox level-independent formation of 51.
Figure 17. Syntheses of γ-butyrolactones via ruthenium-catalyzed hydrohydroxyalkylation. (a) Syntheses of spiro-γ-butyrolactones from diols and methyl acrylate; (b) Syntheses of polysubstituted 2,3’-spirooxindole-γ-butyrolactones from N-benzyl-3-hydroxyoxindole and acrylic esters; (c) Syntheses of α-exo-methylene-γ-butyrolactones from hydroxyl-substituted methacrylate and diols; (d) Redox level-independent formation of 51.
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Figure 18. Asymmetric synthesis of α-exo-methylene γ-butyrolactone via chromium-catalyzed 2-(alkoxycarbonyl)allylation and lactonization and total synthesis of (+)-methylenolactocin.
Figure 18. Asymmetric synthesis of α-exo-methylene γ-butyrolactone via chromium-catalyzed 2-(alkoxycarbonyl)allylation and lactonization and total synthesis of (+)-methylenolactocin.
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Figure 19. Asymmetric synthesis of 2,3′-spirooxindole-α-exo-methylene γ-butyrolactone via indium-catalyzed amide allylation and lactonization.
Figure 19. Asymmetric synthesis of 2,3′-spirooxindole-α-exo-methylene γ-butyrolactone via indium-catalyzed amide allylation and lactonization.
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Figure 20. Asymmetric syntheses of 2,3′-spirooxindole-γ-butyrolactone via NHC-catalyzed homoenolate annulation. (a,b) NHC-catalyzed 2,3′-spirooxindole-γ-butyrolactone formation from enals; (c,d) NHC-catalyzed 2,3′-spirooxindole-γ-butyrolactone formation from carboxylic acids; (e) NHC-catalyzed 2,3′-spirooxindole-γ-butyrolactone formation from aryl esters.
Figure 20. Asymmetric syntheses of 2,3′-spirooxindole-γ-butyrolactone via NHC-catalyzed homoenolate annulation. (a,b) NHC-catalyzed 2,3′-spirooxindole-γ-butyrolactone formation from enals; (c,d) NHC-catalyzed 2,3′-spirooxindole-γ-butyrolactone formation from carboxylic acids; (e) NHC-catalyzed 2,3′-spirooxindole-γ-butyrolactone formation from aryl esters.
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Figure 21. Asymmetric synthesis of 3,4,4-trisubstituted γ-butyrolactones via NHC-catalyzed dynamic kinetic resolution.
Figure 21. Asymmetric synthesis of 3,4,4-trisubstituted γ-butyrolactones via NHC-catalyzed dynamic kinetic resolution.
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Figure 22. Synthesis of γ-butyrolactones via the alcohol-selective C-H activation mediated by photoredox catalysis.
Figure 22. Synthesis of γ-butyrolactones via the alcohol-selective C-H activation mediated by photoredox catalysis.
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Figure 23. Synthesis of γ-butyrolactones via photoorganocatalytic C-H activation.
Figure 23. Synthesis of γ-butyrolactones via photoorganocatalytic C-H activation.
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Figure 24. Asymmetric synthesis of 4,5,5-trisubstituted-γ-butyrolactones via electroreductive C-C bond coupling.
Figure 24. Asymmetric synthesis of 4,5,5-trisubstituted-γ-butyrolactones via electroreductive C-C bond coupling.
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Figure 25. Synthesis of 3,3′-spirooxindole-γ-butyrolactones via peptide coupling reagent-assisted lactonization.
Figure 25. Synthesis of 3,3′-spirooxindole-γ-butyrolactones via peptide coupling reagent-assisted lactonization.
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Figure 26. Asymmetric synthesis of 4,5-disubstituted-γ-butyrolactones via organocatalyzed three-component coupling.
Figure 26. Asymmetric synthesis of 4,5-disubstituted-γ-butyrolactones via organocatalyzed three-component coupling.
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Figure 27. Synthesis of γ-butyrolactones via ruthenium pincer-catalyzed hydrogen autotransfer.
Figure 27. Synthesis of γ-butyrolactones via ruthenium pincer-catalyzed hydrogen autotransfer.
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Figure 28. Synthesis of γ-butyrolactones via ionic liquid-assisted epoxide opening and lactonization.
Figure 28. Synthesis of γ-butyrolactones via ionic liquid-assisted epoxide opening and lactonization.
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Figure 29. Polar radical crossover cycloaddition of the oxidizable alkenes and α,β-unsaturated acids.
Figure 29. Polar radical crossover cycloaddition of the oxidizable alkenes and α,β-unsaturated acids.
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Figure 30. Polar radical crossover cycloaddition of the oxidizable alkenes and O-benzyloxime acids.
Figure 30. Polar radical crossover cycloaddition of the oxidizable alkenes and O-benzyloxime acids.
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Figure 31. γ-Butyrolactone synthesis via the photoredox-catalyzed atom-transfer radical addition (ATRA).
Figure 31. γ-Butyrolactone synthesis via the photoredox-catalyzed atom-transfer radical addition (ATRA).
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Figure 32. Synthesis of carbohydrate-based γ-butyrolactones through Mn(OAc)3-mediated radical lactonization.
Figure 32. Synthesis of carbohydrate-based γ-butyrolactones through Mn(OAc)3-mediated radical lactonization.
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Figure 33. Synthesis of γ-butyrolactones bearing quaternary carbon centers via copper-catalyzed cyclopropanol ring-opening cross-coupling reaction.
Figure 33. Synthesis of γ-butyrolactones bearing quaternary carbon centers via copper-catalyzed cyclopropanol ring-opening cross-coupling reaction.
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Figure 34. Synthesis of bicyclic γ-butyrolactones via palladium-catalyzed carbonylation using iron pentacarbonyl.
Figure 34. Synthesis of bicyclic γ-butyrolactones via palladium-catalyzed carbonylation using iron pentacarbonyl.
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Figure 35. Synthesis of C3-substituted γ-butyrolactones via palladium-catalyzed carbonylation cascade in the ionic liquid.
Figure 35. Synthesis of C3-substituted γ-butyrolactones via palladium-catalyzed carbonylation cascade in the ionic liquid.
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Figure 36. (a) Synthesis of thiolated α-alkylidene-γ-butyrolactones via cobalt-catalyzed carbonylation; (b) Synthesis of thiolated α-alkylidene-γ-butyrolactones via palladium-catalyzed carbonylation.
Figure 36. (a) Synthesis of thiolated α-alkylidene-γ-butyrolactones via cobalt-catalyzed carbonylation; (b) Synthesis of thiolated α-alkylidene-γ-butyrolactones via palladium-catalyzed carbonylation.
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Figure 37. Synthesis of oxaspiro-γ-butyrolactones via palladium-catalyzed carbonylative spirolactonization and total synthesis of α-levantanolide and α-levantenolide.
Figure 37. Synthesis of oxaspiro-γ-butyrolactones via palladium-catalyzed carbonylative spirolactonization and total synthesis of α-levantanolide and α-levantenolide.
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Figure 38. Synthesis of 3,3,5-trisubstituted-γ-butyrolactones via rhodium-catalyzed Markovnikov hydroformylation and oxidation.
Figure 38. Synthesis of 3,3,5-trisubstituted-γ-butyrolactones via rhodium-catalyzed Markovnikov hydroformylation and oxidation.
Ijms 22 02769 g038
Ijms 22 02769 g039 550
Figure 39. Asymmetric synthesis of 4-substituted γ-butyrolactones via rhodium-catalyzed hydroformylation and oxidation.
Figure 39. Asymmetric synthesis of 4-substituted γ-butyrolactones via rhodium-catalyzed hydroformylation and oxidation.
Ijms 22 02769 g039
Ijms 22 02769 g040 550
Figure 40. Synthesis of α-alkyledene γ-butyrolactones via Ni(0)-catalyzed carboxylation and total synthesis of (±)-heteroplexisolide E.
Figure 40. Synthesis of α-alkyledene γ-butyrolactones via Ni(0)-catalyzed carboxylation and total synthesis of (±)-heteroplexisolide E.
Ijms 22 02769 g040
Ijms 22 02769 g041 550
Figure 41. Synthesis of γ-butyrolactones and natural products via Rh-catalyzed C-H insertion.
Figure 41. Synthesis of γ-butyrolactones and natural products via Rh-catalyzed C-H insertion.
Ijms 22 02769 g041
Table
Table 1. Approved drugs containing γ-butyrolactone moiety.
Table 1. Approved drugs containing γ-butyrolactone moiety.
EntryNameStructureTarget ProteinDiseaseSourceReference
1Pilocarpine Ijms 22 02769 i001Muscarinic receptorXerostomiaNatural[15]
2Spironolactone Ijms 22 02769 i002Mineralocorticoid receptorHeart failure, HypertensionSynthetic[16]
3Eplerenone Ijms 22 02769 i003Mineralocorticoid receptorHeart failure, HypertensionSynthetic[17]
4Drospirenone Ijms 22 02769 i004Progesterone receptorOral contraceptiveSynthetic[18]
5Podofilox Ijms 22 02769 i005DNA topoisomerase IIGenital wartsNatural[19]
6Etoposide Ijms 22 02769 i006DNA topoisomerase IILung cancer, LeukaemiaSynthetic[20]
7Teniposide Ijms 22 02769 i007DNA topoisomerase IILymphoblastic leukaemiaSynthetic[21]
8Vorapaxar Ijms 22 02769 i008Protease-activated receptorThrombotic cardiovascular eventsSynthetic[22]
Table
Table 2. Representative biologically active γ-butyrolactones.
Table 2. Representative biologically active γ-butyrolactones.
EntryPharmacological ActivityStructureNameBioassaySourceReference
1Anti-inflammation Ijms 22 02769 i009(3aS,9bR)-8-((2-Bromobenzyl)oxy)-6,9-dimethyl-3-methylene-3,3a,4,5-tetrahydronaphtho[1,2-b]furan-2(9bH)-oneUbeH5c binding assay
(Kd = 0.283 μM)
Therapeutic effect on adjuvant arthritis rat model		Synthetic[23,24]
2 Ijms 22 02769 i0103-((4-((4-Fluorobenzyl)oxy)phenyl)(hydroxy)methyl)-5,7-dimethoxyisobenzofuran-1 (3H)-oneInhibition rate of NO production at 10 µM
(95.23 ± 3.21%)
Therapeutic effect on adjuvant arthritis rat model		Synthetic[25,26]
3 Ijms 22 02769 i011Calcaratarin DSuppression of NF-κB activation by reducing p65 nuclear translocation
Suppression of LPS-induced activation of PI3K/Akt pathway		Natural
(Alpinia calcarata)		[27]
4 Ijms 22 02769 i012(3aR,4R,9aS,9bR)-6,9-Dimethyl-3-methylene-2,7-dioxo-2,3,3a,4,5,7,9a,9b-octahydroazuleno[4,5-b]furan-4-yl methacrylateNF-κB inhibition
(IC100 = 10 μM)		Natural
(Viguiera gardneri)		[28]
5Anti-inflammation Ijms 22 02769 i013(1R,3R,4’R,5R,7R)-7-((2,6-Dichloro-7H-purin-7-yl)methyl)-4’-methyl-1-phenyl-4’-vinyldihydro-2’H-spiro[bicyclo[3.2.0]heptane-3,3’-furan]-2’,4-dione
(Biyouyanagin analog)		Inhibition of LPS-induced cytokine productionSynthetic[29]
6 Ijms 22 02769 i014ArctiidilactoneSuppression of LPS-induced NO productionNatural
(Arctium lappa L.)		[30]
7 Ijms 22 02769 i0152-((2S,4S)-4-Hydroxy-5-oxo-4-(1-tosyl-1H-indol-3-yl)tetrahydrofuran-2-yl)acetonitrileCOX2 inhibition
(IC50 < 0.001 uM)		Synthetic[31]
8 Ijms 22 02769 i016CD10847Caspase-1 inhibition
(IC50 = 17 nM)		Synthetic[32]
9 Ijms 22 02769 i017Cinatrin C3Phospholipase A2 inhibition
(IC50 = 70 μM)		Natural (Circinotrichum falcatisporum RF-641)[33]
10Anticancer Ijms 22 02769 i018Protolichesterinic acidCytotoxicity in HeLa cellsNatural
(Lichen metabolites)		[34]
11 Ijms 22 02769 i019(1aR,5E,8E,10aS,13aS,14S,14aR)-1a,5,9-Trimethyl-13-methylene-12-oxo-1a,2,3,4,7,10,10a,12,13,13a,14,14a-dodecahydrooxireno[2’,3’:4,5]cyclotetradeca[1,2-b]furan-14-yl acetateCytotoxicity in RAW 264.7 cell
(IC50 = 5.99 μM)		Natural
(Lobophytum sp.)		[35]
12 Ijms 22 02769 i020Lactoquinoomycin
(Medermycin)		AKT inhibition
(IC50 = 0.149 μM)
Cytotoxicity in MDA468 cells
(IC50 = 0.05 μM)		Natural
(Streptomyces K73)		[36,37]
13 Ijms 22 02769 i021KalafunginAKT inhibition
(IC50 = 0.313 μM)
Cytotoxicity in MDA468 cells
(IC50 = 0.07 μM)		Natural
(Streptomyces tanashiensis)		[36,38]
14 Ijms 22 02769 i022Frenolicin BAKT inhibition
(IC50 = 0.198 μM)
Cytotoxicity in MDA468 cells
(IC50 = 0.06 μM)		Natural
(Streptomyces roseofulvus strain AM-3867)		[36,39]
15Anticancer Ijms 22 02769 i0235-((6-Amino-9H-purin-9-yl)methyl)-5-methyl-3-methylenedihydrofuran-2(3H)-oneCytotoxicity in L1210 cells
(ED50 = 0.3 μg/mL)		Synthetic[40]
16 Ijms 22 02769 i024(E)-N-((2-Amino-6-methylpyrimidin-4-yl)methyl)-3-(((2-oxodihydrofuran-3(2H)-ylidene)methyl)amino)benzenesulfonamideHSP90 binding
(Ki = 1.9 μM)		Synthetic[41]
17Antibiotic Ijms 22 02769 i025LactivicinInhibition of β-Lactamase in Proteus vulgaris
(IC50 = 2.4 μg/mL)		Natural
(Bacteria YK-258 and YK-422)		[42,43]
18 Ijms 22 02769 i026(3aS,5S,6aS)-5-Hydroxyhexahydro-2H-cyclopenta[b]furan-2-oneInhibition of β-lactamase in Klebsiella oxytoca
(IC50 = 15 mg/l)		Synthetic[44]
19Antibiotic Ijms 22 02769 i027N-((3R,3aS,4R,6R,8R,9R,10R,12R,15R,15aS)-9-(((2S,3R,4S,6R)-4-(Dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-15-ethyl-8-methoxy-4,6,8,10,12,15a-hexamethyl-2,5,11,13-tetraoxotetradecahydro-2H-furo[2,3-c][1]oxacyclotetradecin-3-yl)-2-(quinoxalin-2-ylthio)acetamideAntibacterial activity against erythromycin-susceptible Streptococus pyogenes
(MIC = 0.06 μg/mL)		Synthetic[45]
20 Ijms 22 02769 i0282-Ethoxycarbonyl-2-[2-(3-p-chlorophenylthiazol-2- yl)hydrazono]propyl-4,4-dimethylbutanolideAntibacterial activity against Staphylococcus aureusSynthetic[46]
21 Ijms 22 02769 i029(3aS,7aS)-3a,7,7,7a-Tetramethylhexahydrobenzofuran-2(3H)-oneAntibacterial activity against Staphylococcus aureusSynthetic[47]
22 Ijms 22 02769 i030(1aR,10aS,Z)-1a,5-Dimethyl-8-methylene-2,3,6,7,7a,8,10a,10b-octahydrooxireno[2’,3’:9,10]cyclodeca[1,2-b]furan-9(1aH)-oneAntibacterial activity against MRSA
USA300
(MIC = 56.7 μM)		Synthetic[48]
23 Ijms 22 02769 i031(4S,5S)-5-((S)-1-Iodoethyl)-4-(4-isopropylphenyl)dihydrofuran-2(3H)-oneAntimicrobial activity against Proteus mirabilis
(MIC = 0.25 mg/mL)		Synthetic[49,50]
24Antifungal Ijms 22 02769 i032CarabroneFungicidal activity against C. lagenarium
(IC50 = 7.10 µg/mL)		Natural
(Carpesium abrotanoides)		[51]
25 Ijms 22 02769 i0334- (3-Fluorophenyl)-2-methylenebutyrolactoneFungicidal activity against C. lagenarium
(IC50 = 57.9 µM)		Synthetic[52]
26 Ijms 22 02769 i0344-[4-(3-Bromobenzoyloxy)phenyl]-2-methylenebutyrolactoneFungicidal activity against C. lagenarium
(IC50 = 8.76 µM)		Synthetic[53]
27 Ijms 22 02769 i035Leupyrrins A1Fungicidal activity against M. hiemalis
(MIC = 0.3 µg/mL)		Natural
(Sorangium cellulosum)		[54]
28Immunosuppressive Ijms 22 02769 i036(E)-3-(3,4-Dimethoxyphenyl)-N-(1-oxo-1,3-dihydroisobenzofuran-5-yl)acrylamideInhibition of T cells proliferation
(IC50 = 0.029 μM)		Synthetic[57]
29Immunosuppressive Ijms 22 02769 i037(4S,5S)-5-((1S,2S)-2-Hydroxy-2-methyl-5-oxocyclopent-3-en-1-yl)-3-methylene-4-(3-oxobutyl)dihydrofuran-2(3H)-oneInhibition of T lymphocyte proliferation
(IC50 = 1.0 μM)		Natural
(Artemisia argyi)		[58]
30 Ijms 22 02769 i038(3S,3aS,9bR)-8-((1-(Benzo[d][1,3]dioxol-5-yl)-1H-1,2,3-triazol-5-yl)methoxy)-3,6,9-trimethyl-3a,4,5,9b-tetrahydronaphtho[1,2-b]furan-2(3H)-one
(α-Santonin derivative)		Suppression of LPS-induced B-cell proliferation
(50% at 10 μM)		Synthetic[59]
31 Ijms 22 02769 i039KinsenosideVGEFR2 binding
Therapeutic effect on autoimmune hepatitis in DCs/Hepa1-6 AIH
mouse model		Natural
(Anoectochilus roxburghii)		[60,61]
32Neuroprotective Ijms 22 02769 i040(3R,4R)-4-(4-Hydroxy-3-methoxyphenyl)-3-(4-methoxyphenyl)dihydrofuran-2(3H)-oneNeuroprotective activity in SH-SY5Y cells Natural
(Cinnamomum
cassia)		[62]
33Neuroprotective Ijms 22 02769 i041Japonipene CNeuroprotective activity in SH-SY5Y cellsNatural
(Petasites japonicas)		[63]
34 Ijms 22 02769 i0423-Benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3H)-one (3BDO)PC 12 cell viability assay
Alleviation of memory deficits in AβPP/PS1
transgenic mice		Synthetic[64,65]
35Antioxidant Ijms 22 02769 i043Styraxlignolide EDPPH Radical-Scavenging Activity
(IC50 = 194 µM)		Natural
(Styrax japonica)		[66]
36 Ijms 22 02769 i044Norstictic acidSuperoxide scavenging Activity
(IC50 = 580 µM)		Natural
(Usnea articulate)		[67]
37Hypoglycemic Ijms 22 02769 i045Butyrolactone Iα-Glucosidase inhibition
Multiple anti-type 2 diabetic activities in db/db mice		Natural
(Aspergillus terreus)		[68]
38Hypoglycemic Ijms 22 02769 i046BL-3PTP1B Inhibitory AssaySynthetic[69]
Table
Table 3. Radical precursors in photoredox-catalyzed γ-butyrolactone synthesis.
Table 3. Radical precursors in photoredox-catalyzed γ-butyrolactone synthesis.
EntryRR-RPPCRef
1ArylArN2+BF4-Ru(bpy)3(PF6)2[97]
2CF3Umemoto’s reagentRu(bpy)3(PF6)2[98]
3AlkylNHP esterIr(ppy)2(dtbbpy)PF6[99]
C = photocatalyst, RP = radical precursors.
Table
Table 4. Recent reports for γ-butyrolactone synthesis from 1,4-butanediol.
Table 4. Recent reports for γ-butyrolactone synthesis from 1,4-butanediol.
Ijms 22 02769 i047
EntryMethodCatalystRef
1Vapor phase reactionCu-SiO2 nonocomposite[154]
2Vapor phase reactionSiO2 supported Cu, Ca, Sr or Br promoter[155]
3 1Vapor phase reactionMgO supported Cu[156]
4 2Vapor phase reactionCaAlO supported Cu[157]
5 3Vapor phase reactionMgO supported Cu, Co3O4 promoter[158]
6 4Vapor phase reactionMgO supported Cu[159]
7Vapor phase reactionZrO2 supported Cu, La2O3 promoter[160]
8 5Vapor phase reactionCeO2-Al2O3 supported Cu[161]
9 6Continuous flow reactionAlOx supported Cu nanoparticle[162]
10Chemoenzymatic reactionType II FMO-E and HLADH[163]
11Chemoenzymatic reactionHLADH[164]
12Heterogeneous solution phase reactionSnO2 supported Au[165]
13Heterogeneous solution phase reactionMn2O3 supported Au[166]
15Homogeneous solution phase reactionCu/nitroxyl[167]
16Homogeneous solution phase reactionFe complex 143[168]
17Homogeneous solution phase reactionFe complex 144[169]
18Homogeneous solution phase reactionFe complex 145[170]
19Homogeneous solution phase reactionFe complex 146[171]
1 Simultaneous hydrogenation of acetophenone; 2 Simultaneous hydrogenation of furfural alcohol; 3 Simultaneous hydrogenation of nitrobenzene; 4 Simultaneous hydrogenation of ortho-chloronitrobenzene.5 Simultaneous hydrogenation of benzaldehyde; 6 Simultaneous hydrogenolysis of furfural derivatives.
Table
Table 5. Summary of synthetic methodologies for the synthesis of γ-butyrolactones (2010-2020).
Table 5. Summary of synthetic methodologies for the synthesis of γ-butyrolactones (2010-2020).
SectionBond FormationReactionPage
3.1 Ijms 22 02769 i048Oxidative lactonization12
Halolactonization14
Acid-promoted cyclopropane opening15
Au-catalyzed oxaallylation16
Photoredox-catalyzed lactonization17
3.2 Ijms 22 02769 i049Transition-metal catalyzed C-C bond coupling18
NHC-catalyzed C-C bond coupling20
Photoredox-catalyzed C-C bond coupling23
Miscellsious γ-butyrolactone formation24
3.3 Ijms 22 02769 i050Ruthenium pincer-catalyzed hydrogen autotransfer27
Ionic liquid-assisted epoxide opening and lactonization27
3.4 Ijms 22 02769 i051Polar radical crossover cycloaddition (PRCC)28
Atom-transfer radical addition (ATRA)29
Mn(OAc)3-mediated radical lactonization30
Copper-catalyzed cyclopropanol ring-opening cross-coupling30
3.5 Ijms 22 02769 i052Carbonylative lactonization31
Hydroformylation-oxidation33
Carboxylation-lactonization35
3.6 Ijms 22 02769 i053C-H insertion36
3.7 Ijms 22 02769 i054Oxidative C2-O1 bond formation37
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Hur, J.; Jang, J.; Sim, J. A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones. Int. J. Mol. Sci. 2021, 22, 2769. https://doi.org/10.3390/ijms22052769

AMA Style

Hur J, Jang J, Sim J. A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones. International Journal of Molecular Sciences. 2021; 22(5):2769. https://doi.org/10.3390/ijms22052769

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Hur, Joonseong, Jaebong Jang, and Jaehoon Sim. 2021. "A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones" International Journal of Molecular Sciences 22, no. 5: 2769. https://doi.org/10.3390/ijms22052769

APA Style

Hur, J., Jang, J., & Sim, J. (2021). A Review of the Pharmacological Activities and Recent Synthetic Advances of γ-Butyrolactones. International Journal of Molecular Sciences, 22(5), 2769. https://doi.org/10.3390/ijms22052769

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