Chemistry

Research

15 pages, 5017 KiB

Open AccessArticle

Preparation and Chiral HPLC Separation of the Enantiomeric Forms of Natural Prostaglandins

by Márton Enesei, László Takács, Enikő Tormási, Adrienn Tóthné Rácz, Zita Róka, Mihály Kádár and Zsuzsanna Kardos

Chemistry 2020, 2(3), 727-741; https://doi.org/10.3390/chemistry2030047 - 18 Aug 2020

Viewed by 4503

Abstract

Four enantiomeric forms of natural prostaglandins, ent-PGF_2α ((−)-1), ent-PGE₂ ((+)-2) ent-PGF_1α ((−)-3), and ent-PGE₁ ((+)-4) have been synthetized in gram scale by Corey synthesis used in the [...] Read more.

Four enantiomeric forms of natural prostaglandins, ent-PGF_2α ((−)-1), ent-PGE₂ ((+)-2) ent-PGF_1α ((−)-3), and ent-PGE₁ ((+)-4) have been synthetized in gram scale by Corey synthesis used in the prostaglandin plants of CHINOIN, Budapest. Chiral HPLC methods have been developed to separate the enantiomeric pairs. Enantiomers of natural prostaglandins can be used as analytical standards to verify the enantiopurity of synthetic prostaglandins, or as biomarkers to study oxidation processes in vivo. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Figure 1

12 pages, 4826 KiB

Open AccessCommunication

Peptide Binding Sites of Connexin Proteins

by Ágnes Simon, Csaba Magyar, László Héja and Julianna Kardos

Chemistry 2020, 2(3), 662-673; https://doi.org/10.3390/chemistry2030042 - 14 Jul 2020

Cited by 7 | Viewed by 3437

Abstract

Intercellular gap junction (GJ) contacts formed by the coupling of connexin (Cx) hemichannels (HCs) embedded into the plasma membranes of neighboring cells play significant role in the development, signaling and malfunctions of mammalian tissues. Understanding and targeting GJ functions, however, calls for finding [...] Read more.

Intercellular gap junction (GJ) contacts formed by the coupling of connexin (Cx) hemichannels (HCs) embedded into the plasma membranes of neighboring cells play significant role in the development, signaling and malfunctions of mammalian tissues. Understanding and targeting GJ functions, however, calls for finding valid Cx subtype-specific inhibitors. We conjecture the lack of information about binding interactions between the GJ interface forming extracellular EL1 and EL2 loops and peptide mimetics designed to specifically inhibit Cx43HC coupling to Cx43GJ. Here, we explore active spots at the GJ interface using known peptide inhibitors that mimic various segments of EL1 and EL2. Binding interactions of these peptide inhibitors and the non-peptide inhibitor quinine has been modelled in combination with the use of blind docking molecular mechanics (MM). The neuron-specific Cx36HC and astrocyte-specific Cx43HC subtypes were modelled with a template derived from the high-resolution structure of Cx26GJ. GJ-coupled and free Cx36HC and Cx43HC models were obtained by dissection of GJs (GJ-coupled) followed by 50 ns molecular dynamics (free). Molecular mechanics (MM) calculations were performed by the docking of inhibitors, explicitly the designed Cx43 EL1 or EL2 loop sequence mimetics (GAP26, P5 or P180–195, GAP27, Peptide5, respectively) and the Cx36 subtype-specific quinine into the model structures. In order to explore specific binding interactions between inhibitors and CxHC subtypes, MM/Generalized Born Surface Area (MM/GBSA) ΔG_bind values for representative conformers of peptide mimetics and quinine were evaluated by mapping the binding surface of Cx36HC and Cx43HC for all inhibitors. Quinine specifically contacts Cx36 EL1 residues V54-C55-N56-T57-L58, P60 and N63. Blocking the vestibule by the side of Cx36HC entry, quinine explicitly interacts with the non-conserved V54, L58, N63 residues of Cx36 EL1. In addition, our work challenges the predicted specificity of peptide mimetics, showing that the docking site of peptides is unrelated to the location of the sequence they mimic. Binding features, such as unaffected EL2 residues and the lack of Cx43 subtype-specificity of peptide mimetics, suggest critical roles for peptide stringency and dimension, possibly pertaining to the Cx subtype-specificity of peptide inhibitors. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Figure 1

13 pages, 2329 KiB

Open AccessArticle

Synthesis of Naphthoxazinones in a One-Pot Two-Step Manner by the Application of Propylphosphonic Anhydride (T3P^®)

by Valentina Varga, Péter Ábrányi-Balogh and Mátyás Milen

Chemistry 2020, 2(2), 600-612; https://doi.org/10.3390/chemistry2020037 - 16 Jun 2020

Cited by 2 | Viewed by 4283

Abstract

A sequential one-pot two-step protocol has been elaborated for the synthesis of naphthoxazinones from 2-naphthol, methyl carbamate, and aromatic aldehydes. First, a three-component reaction was optimized with the dehydrating additive propylphosphonic anhydride (T3P^®), resulting in 1-carbamatoalkyl 2-naphthols in good to excellent [...] Read more.

A sequential one-pot two-step protocol has been elaborated for the synthesis of naphthoxazinones from 2-naphthol, methyl carbamate, and aromatic aldehydes. First, a three-component reaction was optimized with the dehydrating additive propylphosphonic anhydride (T3P^®), resulting in 1-carbamatoalkyl 2-naphthols in good to excellent yields. Following the successful multicomponent approach, intramolecular acylation was performed at high temperature, again with the contribution of T3P^®, resulting in naphthoxazinone derivatives in moderate yields. These two steps were optimized together in one-pot as well, and the sequential rise in the requisite temperature eventuated the optimal procedure for the multistep cascade. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Graphical abstract

Review

Jump to: Research, Other

17 pages, 5548 KiB

Open AccessReview

Membrane-Supported Recovery of Homogeneous Organocatalysts: A Review

by Péter Kisszékelyi, Sándor Nagy, Zsuzsanna Fehér, Péter Huszthy and József Kupai

Chemistry 2020, 2(3), 742-758; https://doi.org/10.3390/chemistry2030048 - 27 Aug 2020

Cited by 10 | Viewed by 4309

Abstract

As catalysis plays a significant role in the development of economical and sustainable chemical processes, increased attention is paid to the recovery and reuse of high-value catalysts. Although homogeneous catalysts are usually more active and selective than the heterogeneous ones, both catalyst recycling [...] Read more.

As catalysis plays a significant role in the development of economical and sustainable chemical processes, increased attention is paid to the recovery and reuse of high-value catalysts. Although homogeneous catalysts are usually more active and selective than the heterogeneous ones, both catalyst recycling and product separation pose a challenge for developing industrially feasible methods. In this respect, membrane-supported recovery of organocatalysts represents a particularly useful tool and a valid option for organocatalytic asymmetric synthesis. However, catalyst leaching/degradation and a subsequent decrease in selectivity/conversion are significant drawbacks. As the effectivity of the membrane separation depends mainly on the size of the catalyst in contrast to the other solutes, molecular weight enlargement of small organocatalysts is usually necessary. In the last few years, several synthetic methodologies have been developed to facilitate their recovery by nanofiltration. With the aim of extending the possibilities for the membrane-supported recovery of organocatalysts further, this contribution presents a review of the existing synthetic approaches for the molecular weight enlargement of organocatalysts. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Figure 1

13 pages, 2700 KiB

Open AccessReview

Results in Chemistry of Natural Organic Compounds. Synthesis of New Anticancer Vinca Alkaloids and Flavone Alkaloids

by Szabolcs Mayer, András Keglevich, Csilla Sepsey Für, Hedvig Bölcskei, Viktor Ilkei, Péter Keglevich and László Hazai

Chemistry 2020, 2(3), 714-726; https://doi.org/10.3390/chemistry2030046 - 10 Aug 2020

Cited by 9 | Viewed by 5110

Abstract

The antitumor indole–indoline alkaloids of the evergreen Catharanthus roseus—namely vinblastine and vincristine—are widely used in chemotherapy of cancer. Many efforts were made to synthesize more efficient derivatives with less side-effect. The 14,15-cyclopropane derivative of vinblastine was synthesized successfully by a five-step procedure [...] Read more.

The antitumor indole–indoline alkaloids of the evergreen Catharanthus roseus—namely vinblastine and vincristine—are widely used in chemotherapy of cancer. Many efforts were made to synthesize more efficient derivatives with less side-effect. The 14,15-cyclopropane derivative of vinblastine was synthesized successfully by a five-step procedure starting from vindoline. Vincristine, vinorelbine and several derivatives condensed with a cyclopropane ring were synthesized. Various hybrid molecules were prepared by the coupling reaction of vindoline and methyl ester of tryptophan, which were conjugated by carrier peptides of octaarginine. Studying the halogenation reactions of vindoline and catharanthine some fluorine derivatives were obtained which showed promising antitumor activity on various tumor types. The synthesis of the Aspidospermane alkaloid bannucine and 5′-epibannucine were carried out using N-acyliminium intermediates. The same intermediate was also applied in the first synthesis of sessiline. The research group have synthesized of flavonoid alkaloids: dracocephins A and B. Further three flavonoid alkaloids, namely 8-(2”-pyrrolidinon-5′′-yl)quercetin, 6-(2′′-pyrrolidinon-5′′-yl)-(−)- and 8-(2′′-pyrrolidinon-5′′-yl)-(−)-epicatechin were prepared by acid-catalyzed regioselective Mannich reaction starting from the corresponding flavonoid precursor. Vindoline was also coupled to synthetic pharmacophores, such as triphenylphosphine and various N-heterocycles. Some of these hybrid molecules showed significant antitumor activity. Furthermore, 7-OH and 7-NH modified flavonoid derivatives were synthesized by a regioselective alkylation followed by Smiles rearrangement and hydrolysis. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Figure 1

17 pages, 5940 KiB

Open AccessFeature PaperReview

Synthesis and Chemistry of 1,2,3-Benzothiadiazine 1,1-Dioxide Derivatives: A Comprehensive Overview

by Imre Gyűjtő, Gyula Simig, Márta Porcs-Makkay and Balázs Volk

Chemistry 2020, 2(3), 674-690; https://doi.org/10.3390/chemistry2030043 - 21 Jul 2020

Cited by 4 | Viewed by 6016

Abstract

1,2,4-Benzothiadiazine 1,1-dioxide derivatives (e.g., chlorothiazide, hydrochlorothiazide) have been long used in the human therapy as diuretic and antihypertensive agents. Marketed drugs containing the structurally related phthalazinone scaffold are applied for the treatment of various diseases ranging from ovarian cancer to diabetes and allergy. [...] Read more.

1,2,4-Benzothiadiazine 1,1-dioxide derivatives (e.g., chlorothiazide, hydrochlorothiazide) have been long used in the human therapy as diuretic and antihypertensive agents. Marketed drugs containing the structurally related phthalazinone scaffold are applied for the treatment of various diseases ranging from ovarian cancer to diabetes and allergy. 1,2,3-Benzothiadiazine 1,1-dioxides combine the structural features of these two compound families, which led to their more intensive research since the 1960s. In the present review, we summarize the literature of this period of more than half a century, including all scientific papers and patent applications dealing with the synthesis and reactions of this compound family, briefly hinting at their potential therapeutic application as well. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Graphical abstract

Other

Jump to: Research, Review

28 pages, 5488 KiB

Open AccessPerspective

Carbohydrate-Based Azacrown Ethers in Asymmetric Syntheses

by István Orbán, Péter Bakó and Zsolt Rapi

Chemistry 2021, 3(2), 550-577; https://doi.org/10.3390/chemistry3020039 - 15 Apr 2021

Cited by 8 | Viewed by 3191

Abstract

Carbohydrate-based crown ethers represent a special group of chiral phase transfer catalysts. Several derivatives of these macrocycles have been synthesized in our research group. Among these compounds, monoaza-15-crown-5 lariat ethers proved to be effective phase transfer and enantioselective catalysts in certain reactions. Those [...] Read more.

Carbohydrate-based crown ethers represent a special group of chiral phase transfer catalysts. Several derivatives of these macrocycles have been synthesized in our research group. Among these compounds, monoaza-15-crown-5 lariat ethers proved to be effective phase transfer and enantioselective catalysts in certain reactions. Those chiral azacrown ethers incorporating various carbohydrate moieties in the macrocyclic structure are reviewed, which generated asymmetric induction in reactions, such as Michael addition, epoxidation of enones, Darzens condensation and Michael-initiated ring-closure (MIRC) reaction. Effects on the catalytic activity of the structural changes are the focus. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Scheme 1

12 pages, 2097 KiB

Open AccessPerspective

New Spiro[cycloalkane-pyridazinone] Derivatives with Favorable Fsp³ Character

by Csilla Sepsey Für and Hedvig Bölcskei

Chemistry 2020, 2(4), 837-848; https://doi.org/10.3390/chemistry2040055 - 6 Oct 2020

Cited by 3 | Viewed by 3973

Abstract

The large originator pharmaceutical companies need more and more new compounds for their molecule banks, because high throughput screening (HTS) is still a widely used method to find new hits in the course of the lead discovery. In the design and synthesis of [...] Read more.

The large originator pharmaceutical companies need more and more new compounds for their molecule banks, because high throughput screening (HTS) is still a widely used method to find new hits in the course of the lead discovery. In the design and synthesis of a new compound library, important points are in focus nowadays: Lipinski’s rule of five (RO5); the high Fsp³ character; the use of bioisosteric heterocycles instead of aromatic rings. With said aim in mind, we have synthesized a small compound library of new spiro[cycloalkane-pyridazinones] with 36 members. The compounds with this new scaffold may be useful in various drug discovery projects. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Figure 1

9 pages, 2574 KiB

Open AccessPerspective

Effect of the Enantiomeric Ratio of Eutectics on the Results and Products of the Reactions Proceeding with the Participation of Enantiomers and Enantiomeric Mixtures

by Emese Pálovics, Dorottya Fruzsina Bánhegyi and Elemér Fogassy

Chemistry 2020, 2(3), 787-795; https://doi.org/10.3390/chemistry2030051 - 21 Sep 2020

Cited by 2 | Viewed by 3088

Abstract

This perspective is focused on the main parameters determining the results of crystallization of enantiomers or enantiomeric mixtures. It was shown that the ratio of supramolecular and helical associations depends on the eutectic composition of the corresponding enantiomeric mixture. The M and P [...] Read more.

This perspective is focused on the main parameters determining the results of crystallization of enantiomers or enantiomeric mixtures. It was shown that the ratio of supramolecular and helical associations depends on the eutectic composition of the corresponding enantiomeric mixture. The M and P ratios together with the self-disproportionation (SDE) of enantiomers define the reaction of the racemic compound with the resolving agent. Eventually, each chiral molecule reacts with at least two conformers with different degrees of M and P helicity. The combined effect of the configuration, charge distribution, constituent atoms, bonds, flexibility, and asymmetry of the molecules influencing their behavior was also summarized. Full article

(This article belongs to the Special Issue Organic Chemistry Research in Hungary)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Organic Chemistry Research in Hungary

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (9 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI