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Article

Enantioselective Synthesis of the Sex Pheromone of Sitodiplosis mosellana (Géhin) and Its Stereoisomers

by
Jianan Wang
1,
Xiaoyang Li
1,
Yun Zhou
2,
Qinghua Bian
1 and
Jiangchun Zhong
1,*
1
Department of Applied Chemistry, China Agricultural University, Beijing 100193, China
2
Institute of Industrial Crops, Shandong Academy of Agricultural Sciences, Jinan 250100, China
*
Author to whom correspondence should be addressed.
Molecules 2025, 30(3), 671; https://doi.org/10.3390/molecules30030671
Submission received: 29 December 2024 / Revised: 25 January 2025 / Accepted: 29 January 2025 / Published: 3 February 2025
(This article belongs to the Special Issue Current Development of Asymmetric Catalysis and Synthesis)
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Abstract

:
(2S,7S)-2,7-Nonanediyl dibutyrate is the sex pheromone of Sitodiplosis mosellana (Géhin). In this study, this sex pheromone and its three stereoisomers were prepared. Central to this strategy was the ring opening of chiral epoxide with an alkynyllithium and the hydrogenation of the triple bond. Moreover, this approach consisted of six steps, and the total yields were 59–64%.

1. Introduction

The orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), is a notorious pest worldwide [1,2], which has caused significant yield losses in wheat (Triticum aestivum Linnaeus) [3,4]. The adult females often oviposit on wheat heads, and the larvae feed on the developing seeds [5]. This leads to shriveling and presprouting damage, resulting in a reduction in both the yield and quality of wheat harvested [6,7]. The current integrated pest management programs for S. mosellana mainly rely on pesticides [8,9], the conservation of natural enemies [10] and resistant cultivars [11,12].
Pheromone-based pest control is an alternative strategy with the advantages of environmental friendliness, high efficiency and rarely inducing pest resistance [13,14]. In 2000, Gries identified that the sex pheromone of S. mosellana was (2S,7S)-2,7-nonanediyl dibutyrate ((2S,7S)-1) (Figure 1) via coupled gas chromatographic-electroantennographic detection (GC-EAD) with GC–mass spectrometry (MS) and trap experiments in wheat fields [15]. Furthermore, Gries prepared (2S,7S)-1 using CuI, which catalyzed the reaction of S-propylene oxide with Grignard reagent, and through the hydrolytic kinetic resolution of epoxide using Jacobsen’s catalyst [15]. The pheromone could be utilized for monitoring and trapping the orange wheat blossom midge [16,17], which has attracted significant interest from chemists. Previous syntheses have employed various approaches, including chiral sources of (S)-but-3-yn-2-ol [18,19] and (S)-5-hexen-2-ol [20], and the esterification of racemic nonanediyl dibutyrate using Pseudomonas cepacia Burkh lipase [21]. To further research the biological activities of the sex pheromone, herein, new and efficient synthesis of the sex pheromone of S. mosellana and its stereoisomers (Figure 1) is achieved.

2. Results and Discussion

2.1. Retrosynthetic Analysis

The retrosynthetic analysis of the sex pheromone of S. mosellana (2S,7S)-1 is shown in Scheme 1. The target pheromone (2S,7S)-1 was obtained through the acylation of alkynyl diol (2S,7S)-8 with butyric anhydride (10). The chiral secondary hydroxy at C2 of (2S,7S)-8 was envisioned to be constructed through the addition of (S)-2-methyloxirane ((S)-6) with chiral TBDPS ether (S)-5 and n-BuLi. The other stereocenter of (2S,7S)-8 was obtained from the chiral source (S)-2-ethyloxirane ((S)-2). Following a similar procedure for sex pheromone (2S,7S)-1, its stereoisomers (2R,7S)-1, (2S,7R)-1, (2R,7R)-1 were prepared.

2.2. Synthesis of Chiral TBDPS Ethers

Based on the retrosynthetic analysis of the sex pheromone (2S,7S)-1, our synthesis started from the preparation of chiral TBDPS ethers (S)- and (R)-5 (Scheme 2). The reaction of (S)-2-ethyloxirane ((S)-2) with lithium acetylide ethylenediamine complex (3) in DMSO yielded (S)-hex-5-yn-3-ol ((S)-4) (87% yield) [22,23]. The specific rotation of chiral alcohol (S)-4 was identical to that in the literature data [24]. The secondary hydroxy of (S)-4 was then protected by a treatment with TBDPSCl and imidazole to provide chiral TBDPS ether (S)-5 in a 95% yield [25,26]. Similarly, (R)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane ((R)-5) was prepared via the ring opening of (R)-2-ethyloxirane ((R)-2) with lithium acetylide ethylenediamine complex (3) and the protection of hydroxy of (R)-4 with TBDPSCl.

2.3. Synthesis of Sex Pheromone of S. mosellana

With the key chiral block (S)- 5 in hand, we next prepared the sex pheromone of S. mosellana (Scheme 3). In the presence of boron trifluoride-diethyl etherate, the addition of (S)-2-methyloxirane ((S)-6) with alkynyllithium, prepared in situ from the chiral TBDPS ether (S)-5 and n-BuLi, provided (2S,7S)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2S,7S)-7) almost quantitatively [27,28]. The subsequent deprotection with TBAF gave (2S,7S)-non-4-yne-2,7-diol ((2S,7S)-8) in a 93% yield [29]. Finaly, the hydrogenation of the triple bond of chiral alkynyl diol (2S,7S)-8 resulted in the formation of (2S,7S)-nonane-2,7-diol ((2S,7S)-9) [30,31], which was treated with butyric anhydride (10) to yield (2S,7S)-nonane-2,7-diyl dibutyrate ((2S,7S)-1) [32,33]. The NMR spectra, HRMS, and specific rotation of the sex pheromone (2S,7S)-1 matched those in reference [20].

2.4. Synthesis of Stereoisomers of S. mosellana Sex Pheromone

Having achieved the synthesis of the sex pheromone of S. mosellana, we next investigated the preparation of its stereoisomers (Scheme 4). According to a similar procedure for the sex pheromone (2S,7S)-1, its stereoisomers (2R,7S)-1, (2S,7R)-1 and (2R,7R)-1 were synthesized from chiral TBDPS ether (S)-5 and (R)-2-methyloxirane ((R)-6); chiral TBDPS ether (R)-5 and (S)-2-methyloxirane ((S)-6); and chiral TBDPS ether (R)-5 and (R)-2-methyloxirane ((R)-6), respectively. The structures of these stereoisomers were characterized by specific rotation, NMR spectra and HRMS (The NMR spectra are available in the Supplementary Materials).

3. Materials and Methods

3.1. General Information

Unless otherwise stated, all reactions were performed under an argon atmosphere with a Schlenk line system. All commercial reagents and starting materials were used as received. The chiral reagents of (S)-2-ethyloxirane (268 RMB/100 mL), (R)-2-ethyloxirane (268 RMB/100 mL), (S)-2-methyloxirane (104 RMB/5 g) and (R)-2-methyloxirane (240 RMB/5 g) were purchased from Anhui Senrise Technology Co., Ltd., (Anhui, China). Dichloromethane, tetrahydrofuran, methanol and dimethyl sulfone were purchased from Beijing Ouhe Technology Co., Ltd., (Beijing, China), and purified according to standard procedures. 1H NMR and 13C NMR spectra were recorded on a Bruker AscendTM 500 MHz spectrometer (Bruker Corporation, Billerica, MA, USA) at 500 MHz and 125 MHz, respectively. The chemical shifts were reported in ppm using TMS (0.00 ppm) and CDCl3 (77.16 ppm) as internal standards. High-resolution mass spectra (HRMS) were obtained on a Waters LCT PremierTM (Waters Corporation, Milford, MA, USA) with an electrospray ionization (ESI) mass spectrometer. Optical rotations were measured on a Rudolph AUTOPOL-IV polarimeter (Rudolph Research Analytical, Flanders, NJ, USA).

3.2. Synthesis of (S)-5-hexyn-3-ol ((S)-4)

Under an argon atmosphere, (S)-2-ethyloxirane ((S)-2) (5.00 g, 69.35 mmol, >99% ee, 1.0 equiv.) was added slowly to a stirred suspension of lithium acetylide ethylenediamine complex (3) (15.96 g, 173.38 mmol, 2.5 equiv.) in DMSO (100 mL) at 0 °C. The reaction mixture was allowed to warm to room temperature and stirred continuously overnight. The reaction was then quenched by adding cold water (50 mL), followed by extraction with DCM (3 × 30 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield the crude product. The crude product was purified by silica gel column chromatography using an eluent of ethyl acetate and petroleum ether (1:5) to produce (S)-hex-5-yn-3-ol ((S)-4) (5.92 g, 87% yield) as a colorless oil. [α]D25 = +2.78 (c 1.29, CHCl3). Lit. [24] [α]D = +3.00 (c 2.00, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.65–3.60 (m, 1H), 2.39–2.34 (m, 1H), 2.28–2.23 (m, 1H), 2.04 (br s, 1H), 1.98 (t, J = 2.7 Hz, 1H), 1.57–1.45 (m, 2H), 0.89 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 81.0, 71.3, 70.8, 29.2, 27.0, 10.0. HRMS (ESI, m/z): calculated for [M + Na]+ C6H10ONa 121.0624, found: 121.0615.

3.3. Synthesis of (R)-5-hexyn-3-ol ((R)-4)

Using a similar procedure for chiral alcohol (S)-4, the addition of lithium acetylide ethylenediamine complex 3 (15.96 g, 173.38 mmol, 2.5 equiv.) to (R)-2-ethyloxirane ((R)-2) (5.00 g, 69.35 mmol, >99% ee, 1.0 equiv.) yielded (R)-5-Hexyn-3-ol ((R)-4) (5.98 g, 88% yield) as a colorless oil. [α]D25 = −4.45 (c 0.99, CHCl3). Lit. [24] [α]D = −4.00 (c 2.00, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.65–3.60 (m, 1H), 2.39–2.34 (m, 1H), 2.28–2.23 (m, 1H), 1.99–1.98 (m, 1H), 1.90–1.88 (m, 1H), 1.55–1.47 (m, 2H), 0.90 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 81.0, 71.3, 70.8, 29.2, 27.0, 10.0. HRMS (ESI, m/z): calculated for [M + Na]+ C6H10ONa 121.0624, found: 121.0612.

3.4. Synthesis of (S)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane ((S)-5)

Under an argon atmosphere, (S)-5-hexyn-3-ol ((S)-4) (8.54 g, 87.00 mmol, 1.0 equiv.) was added slowly to a solution of DMAP (2.13 g, 17.40 mmol, 0.2 equiv.) and imidazole (14.81 g, 217.50 mmol, 2.5 equiv.) in DCM (200 mL) at 0 °C. Subsequently, TBDPSCl (29.12 g, 104.4 mmol, 1.2 equiv.) was added. The mixture was allowed to warm to room temperature and stirred continuously overnight. The reaction was then quenched by adding water (50 mL), followed by a separation of the lower organic phase. The higher aqueous phase was extracted with DCM (3 × 30 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield the crude product. The crude product was purified by silica gel column chromatography using an eluent of ethyl acetate and petroleum ether (1:20) to produce (S)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane ((S)-5) (27.8 g, 95% yield) as a light yellow oil. [α]D25 = −26.58 (c 4.91, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.61–7.58 (m, 4H), 7.30–7.23 (m, 6H), 3.74–3.70 (m, 1H), 2.24–2.14 (m, 2H), 1.76 (t, J = 2.7 Hz, 1H), 1.60–1.47 (m, 2H), 0.97 (s, 9H), 0.74 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 136.03, 136.00, 134.4, 134.2, 129.8, 127.76, 127.69, 81.4, 72.6, 70.1, 28.7, 27.1, 26.0, 19.5, 9.1. HRMS (ESI, m/z): calculated for [M + H]+ C22H29OSi 337.1982, found: 339.1954.

3.5. Synthesis of (R)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane ((R)-5)

Using a similar procedure for chiral TBDPS ether (S)-5, the protection of (R)-5-hexyn-3-ol ((R)-4) (8.54 g, 87.00 mmol, 1.0 equiv.) with TBDPSCl (29.12 g, 104.40 mmol, 1.2 equiv.) yielded (R)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane ((R)-5) (26.9 g, 92% yield) as a light yellow oil. [α]D25 = +25.77 (c 10.58, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.62–7.58 (m, 4H), 7.33–7.25 (m, 6H), 3.75–3.71 (m, 1H), 2.24–2.15 (m, 2H), 1.79 (t, J = 2.7 Hz, 1H), 1.58–1.50 (m, 2H), 0.98 (s, 9H), 0.76 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 136.04, 136.01, 134.4, 134.2, 129.8, 127.69, 127.66, 127.64, 81.5, 72.6, 70.0, 28.7, 27.1, 26.0, 19.5, 9.1. HRMS (ESI, m/z): calculated for [M + H]+ C22H29OSi 337.1982, found: 339.1956.

3.6. Synthesis of (2S,7S)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2S,7S)-7)

Under an argon atmosphere, n-BuLi (2.69 mL, 2.4 M in n-hexane, 6.45 mmol, 2.15 equiv.) was added dropwise to a stirred solution of (S)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane ((S)-5) (2.54 g, 7.50 mmol, 2.5 equiv.) in THF (15 mL) at −78 °C. The mixture was stirred for 1.5 h at the same temperature, and a solution of (S)-2-methyloxirane ((S)-6) (>99% ee, 174.3 mg, 3.00 mmol, 1.0 equiv.) in THF (1 mL) and boron trifluoride-diethyl etherate (852.0 mg, 6.00 mmol, 2.0 equiv.), which were pre-chilled at −78 °C, was then added. The reaction mixture was allowed to warm to room temperature and stirred continuously for 12 h. The reaction was quenched by adding saturated aqueous NaHCO3 solution (5 mL), followed by separation of the organic phase. The aqueous phase was extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield the crude product. The crude product was purified by silica gel column chromatography using an eluent of ethyl acetate and petroleum ether (1:5) to produce (2S,7S)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2S,7S)-7) (1.15 g, 97% yield) as a colorless oil. [α]D25 = −28.17 (c 1.53, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.63–7.60 (m, 4H), 7.35–7.28 (m, 6H), 3.80–3.74 (m, 1H), 3.72–3.67 (m, 1H), 2.26–2.12 (m, 4H), 1.69 (br s, 1H), 1.57–1.49 (m, 2H), 1.13 (d, J = 6.2 Hz, 3H), 0.99 (s, 9H), 0.77 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 136.0, 134.5, 134.3, 129.73, 129.69, 127.7, 127.6, 80.2, 78.0, 73.0, 66.6, 29.6, 29.0, 27.1, 26.3, 22.3, 19.5, 9.2. HRMS (ESI, m/z): calculated for [M + H]+ C25H35O2Si 395.2401, found: 395.2396.

3.7. Synthesis of (2R,7S)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2R,7S)-7)

Using a similar procedure for chiral TBDPS ether alcohol (2S,7S)-7, the ring opening of (R)-2-methyloxirane (R)-6 (>99% ee, 174.3 mg, 3.00 mmol, 1.0 equiv.) with (S)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane (S)-5 (2.54 g, 7.50 mmol, 2.5 equiv.) and n-BuLi (2.69 mL, 2.4 M in n-hexane, 6.45 mmol, 2.15 equiv.) yielded (2R,7S)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2R,7S)-7) (1.15 g, 97% yield) as a colorless oil. [α]D25 = −30.66 (c 4.84, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.70–7.67 (m, 4H), 7.43–7.35 (m, 6H), 3.87–3.81 (m, 1H), 3.80–3.75 (m, 1H), 2.33–2.20 (m, 4H), 1.99 (br s, 1H), 1.65–1.56 (m, 2H), 1.20 (d, J = 6.1 Hz, 3H), 1.06 (s, 9H), 0.84 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 136.0, 134.5, 134.2, 129.72, 129.68, 127.7, 127.6, 80.2, 78.0, 73.0, 66.6, 29.6, 28.9, 27.1, 26.3, 22.3, 19.5, 9.2. HRMS (ESI, m/z): calculated for [M + H]+ C25H35O2Si 395.2401, found: 395.2401.

3.8. Synthesis of (2S,7R)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2S,7R)-7)

Using a similar procedure for chiral TBDPS ether alcohol (2S,7S)-7, the ring opening of (S)-2-methyloxirane ((S)-6) (>99% ee, 174.3 mg, 3.00 mmol, 1.0 equiv.) with (R)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane ((R)-5) (2.54 g, 7.50 mmol, 2.5 equiv.) and n-BuLi (2.69 mL, 2.4 M in n-hexane, 6.45 mmol, 2.15 equiv.) yielded (2S,7R)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2S,7R)-7) (1.17 g, 99% yield) as a light yellow oil. [α]D25 = +32.25 (c 3.28, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.70–7.67 (m, 4H), 7.43–7.35 (m, 6H), 3.85–3.82 (m, 1H), 3.79–3.75 (m, 1H), 2.33–2.19 (m, 4H), 1.98 (br s, 1H), 1.64–1.57 (m, 2H), 1.20 (d, J = 6.1 Hz, 3H), 1.06 (s, 9H), 0.84 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 136.0, 134.5, 134.2, 129.72, 129.69, 127.7, 127.6, 80.2, 78.0, 73.0, 66.6, 29.6, 28.9, 27.1, 26.3, 22.3, 19.5, 9.2. HRMS (ESI, m/z): calculated for [M + H]+ C25H35O2Si 395.2401, found: 395.2401.

3.9. Synthesis of (2R,7R)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2R,7R)-7)

Using a similar procedure for chiral TBDPS ether alcohol (2S,7S)-7, the ring opening of (R)-2-methyloxirane ((R)-6) (>99% ee, 174.3 mg, 3.00 mmol, 1.0 equiv.) with (R)-tert-butyl(hex-5-yn-3-yloxy)diphenylsilane ((R)-5) (2.54 g, 7.50 mmol, 2.5 equiv.) and n-BuLi (2.69 mL, 2.4 M in n-hexane, 6.45 mmol, 2.15 equiv.) yielded (2R,7R)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2R,7R)-7) (1.12 g, 95% yield) as a light yellow oil. [α]D25 = +22.59 (c 3.40, CHCl3). 1H NMR (500 MHz, CDCl3) δ 7.70–7.67 (m, 4H), 7.43–7.35 (m, 6H), 3.87–3.82 (m, 1H), 3.79–3.75 (m, 1H), 2.33–2.19 (m, 4H), 1.98 (br s, 1H), 1.65–1.56 (m, 2H), 1.20 (d, J = 6.2 Hz, 3H), 1.06 (s, 9H), 0.84 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 136.0, 134.5, 134.2, 129.73, 129.69, 127.7, 127.6, 80.1, 78.0, 73.0, 66.6, 29.6, 28.9, 27.1, 26.3, 22.3, 19.5, 9.2. HRMS (ESI, m/z): calculated for [M + H]+ C25H35O2Si 395.2401, found: 395.2385.

3.10. Synthesis of (2S,7S)-non-4-yne-2,7-diol ((2S,7S)-8)

Under an argon atmosphere, TBAF (4 mL, 1 M in THF, 4.00 mmol, 2.0 equiv.) was added slowly to a stirred solution of (2S,7S)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2S,7S)-7) (790.0 mg, 2.00 mmol, 1.0 equiv.) in THF (5 mL) at 0 °C. The reaction mixture was allowed to warm to room temperature and stirred continuously overnight. The reaction was then quenched by adding water (5 mL), followed by separation of the organic phase. The aqueous phase was extracted with EtOAc (3 × 8 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield the crude product. The crude product was purified by silica gel column chromatography using an eluent of ethyl acetate and petroleum ether (1:2) to produce (2S,7S)-non-4-yne-2,7-diol ((2S,7S)-8) (290.0 mg, 93% yield) as a colorless oil. [α]D25 = +14.47 (c 2.24, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.89–3.84 (m, 1H), 3.61–3.56 (m, 1H), 2.44 (br s, 2H), 2.38–2.30 (m, 2H), 2.26–2.21 (m, 2H), 1.53–1.45 (m, 2H), 1.18 (d, J = 6.3 Hz, 3H), 0.89 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 79.3, 79.2, 71.7, 66.6, 29.4, 29.3, 27.2, 22.4, 10.1. HRMS (ESI, m/z): calculated for [M + H]+ C9H17O2 157.1223, found: 157.1225.

3.11. Synthesis of (2R,7S)-non-4-yne-2,7-diol ((2R,7S)-8)

Using a similar procedure for chiral alkynyl diol (2S,7S)-8, deprotection of (2R,7S)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2R,7S)-7) (790.0 mg, 2.00 mmol, 1.0 equiv.) with TBAF (4 mL, 1 M in THF, 4.00 mmol, 2.0 equiv.) yielded (2R,7S)-non-4-yne-2,7-diol ((2R,7S)-8) (284 mg, 91% yield) as a colorless oil. [α]D25 = −3.83 (c 1.25, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.96–3.90 (m, 1H), 3.68–3.63 (m, 1H), 2.46–2.28 (m, 6H), 1.59–1.53 (m, 2H), 1.25 (d, J = 6.2 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 79.3, 79.2, 71.7, 66.6, 29.4, 29.3, 27.3, 22.4, 10.1. HRMS (ESI, m/z): calculated for [M + H]+ C9H17O2 157.1223, found: 157.1220.

3.12. Synthesis of (2S,7R)-non-4-yne-2,7-diol ((2S,7R)-8)

Using a similar procedure for chiral alkynyl diol (2S,7S)-8, deprotection of (2S,7R)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2S,7R)-7) (790.0 mg, 2.00 mmol, 1.0 equiv.) with TBAF (4 mL, 1 M in THF, 4.00 mmol, 2.0 equiv.) yielded (2S,7R)-non-4-yne-2,7-diol ((2S,7R)-8) (264 mg, 86% yield) as a colorless oil. [α]D25 = +3.18 (c 2.14, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.96–3.90 (m, 1H), 3.67–3.64 (m, 1H), 2.62–2.28 (m, 6H), 1.59–1.54 (m, 2H), 1.25 (d, J = 6.2 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 79.3, 79.2, 71.7, 66.6, 29.4, 29.2, 27.2, 22.4, 10.0. HRMS (ESI, m/z): calculated for [M + H]+ C9H17O2 157.1223, found: 157.1221.

3.13. Synthesis of (2R,7R)-non-4-yne-2,7-diol ((2R,7R)-8)

Using a similar procedure for chiral alkynyl diol (2S,7S)-8, deprotection of (2R,7R)-7-((tert-butyldiphenylsilyl)oxy)non-4-yn-2-ol ((2R,7R)-7) (790.0 mg, 2.00 mmol, 1.0 equiv.) with TBAF (4 mL, 1 M in THF, 4.00 mmol, 2.0 equiv.) yielded (2R,7R)-non-4-yne-2,7-diol ((2R,7R)-8) (293 mg, 94% yield) as a colorless oil. [α]D25 = −20.82 (c 1.13, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.97–3.90 (m, 1H), 3.68–3.63 (m, 1H), 2.46–2.27 (m, 6H), 1.59–1.53 (m, 2H), 1.25 (d, J = 6.3 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 79.4, 79.2, 71.7, 66.6, 29.4, 29.3, 27.3, 22.5, 10.1. HRMS (ESI, m/z): calculated for [M + H]+ C9H17O2 157.1223, found: 157.1220.

3.14. Synthesis of (2S,7S)-nonane-2,7-diol ((2S,7S)-9)

Under a hydrogen atmosphere, (2S,7S)-non-4-yne-2,7-diol ((2S,7S)-8) (180.0 mg, 1.15 mmol, 1.0 equiv.) was add to a stirred solution of Pd/C (18.0 mg, 10%) in MeOH (5 mL) at room temperature. The reaction mixture was stirred continuously overnight under a hydrogen atmosphere, followed by being filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure to yield the crude product. The crude product was purified by silica gel column chromatography using an eluent of ethyl acetate and petroleum ether (1:2) to produce (2S,7S)-nonane-2,7-diol ((2S,7S)-9) (162.0 mg, 88% yield) as a colorless oil. [α]D25 = +14.77 (c 0.87, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.77–3.71 (m, 1H), 3.49–3.44 (m, 1H), 1.58 (br s, 2H), 1.47–1.30 (m, 10H), 1.12 (d, J = 6.2 Hz, 3H), 0.87 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 73.3, 68.1, 39.4, 37.0, 30.3, 25.9, 25.7, 23.7, 10.0. HRMS (ESI, m/z): calculated for [M + H]+ C9H21O2 161.1536, found: 161.1538.

3.15. Synthesis of (2R,7S)-nonane-2,7-diol ((2R,7S)-9)

Using a similar procedure for chiral diol (2S,7S)-9, the hydrogenation of (2R,7S)-non-4-yne-2,7-diol ((2R,7S)-8) (154.0 mg, 0.99 mmol, 1.0 equiv.) catalyzed with Pd/C (15.0 mg, 10%) yielded (2R,7S)-nonane-2,7-diol ((2R,7S)-9) (145.0 mg, 92% yield) as a colorless oil. [α]D25 = +0.56 (c 2.15, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.83–3.77 (m, 1H), 3.55–3.51 (m, 1H), 1.71 (br s, 2H), 1.53–1.40 (m, 8H), 1.37–1.30 (m, 2H), 1.19 (d, J = 6.2 Hz, 3H), 0.94 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 73.3, 68.1, 39.4, 36.9, 30.3, 25.9, 25.8, 23.6, 10.0. HRMS (ESI, m/z): calculated for [M + H]+ C9H21O2 161.1536, found: 161.1538.

3.16. Synthesis of (2S,7R)-nonane-2,7-diol ((2S,7R)-9)

Using a similar procedure for chiral diol (2S,7S)-9, the hydrogenation of (2S,7R)-non-4-yne-2,7-diol ((2S,7R)-8) (180.0 mg, 1.15 mmol, 1.0 equiv.) catalyzed with Pd/C (18.0 mg, 10%) yielded (2S,7R)-nonane-2,7-diol ((2S,7R)-9) (170.0 mg, 92% yield) as a colorless oil. [α]D25 = −1.24 (c 1.93, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.75–3.69 (m, 1H), 3.46–3.43 (m, 1H), 1.85 (br s, 2H), 1.46–1.33 (m, 8H), 1.31–1.24 (m, 2H), 1.11 (d, J = 6.2 Hz, 3H), 0.87 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 73.3, 68.1, 39.3, 36.9, 30.3, 25.9, 25.8, 23.6, 10.0. HRMS (ESI, m/z): calculated for [M + H]+ C9H21O2 161.1536, found: 161.1539.

3.17. Synthesis of (2R,7R)-nonane-2,7-diol ((2R,7R)-9)

Using a similar procedure for chiral diol (2S,7S)-9, the hydrogenation of (2R,7R)-non-4-yne-2,7-diol (2R,7R)-8 (293.0 mg, 1.87 mmol, 1.0 equiv.) catalyzed with Pd/C (30.0 mg, 10%) yielded (2R,7R)-nonane-2,7-diol ((2R,7R)-9) (270.0 mg, 90% yield) as a colorless oil. [α]D25 = −17.76 (c 1.25, CHCl3). 1H NMR (500 MHz, CDCl3) δ 3.76–3.71 (m, 1H), 3.48–3.43 (m, 1H), 1.65 (br s, 2H), 1.47–1.27 (m, 10H), 1.12 (d, J = 6.2 Hz, 3H), 0.87 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 73.3, 68.1, 39.3, 36.9, 30.3, 25.8, 25.7, 23.6, 10.0. HRMS (ESI, m/z): calculated for [M + H]+ C9H21O2 161.1536, found: 161.1538.

3.18. Synthesis of (2S,7S)-nonane-2,7-diyl dibutyrate ((2S,7S)-1)

Under an argon atmosphere, butyric anhydride (10) (95.0 mg, 0.60 mmol, 3.0 equiv.) was added slowly to a stirred solution of (2S,7S)-nonane-2,7-diol ((2S,7S)-9) (32.0 mg, 0.20 mmol, 1.0 equiv.) in anhydrous pyridine (5 mL) at 0 °C. The reaction solution was allowed to warm to room temperature and stirred continuously overnight. The mixture was concentrated under reduced pressure to yield the crude product. The crude product was purified by silica gel column chromatography using an eluent of ethyl acetate and petroleum ether (1:50) to produce (2S,7S)-nonane-2,7-diyl dibutyrate ((2S,7S)-1) (56.0 mg, 94% yield) as a colorless oil. [α]D25 = −2.41 (c 1.16, CHCl3). Lit. [20] [α]D20 =–6.7 (c 0.6, CHCl3). 1H NMR (500 MHz, CDCl3) δ 4.92–4.86 (m, 1H), 4.84–4.79 (m, 1H), 2.26 (dt, J = 11.3, 7.5 Hz, 4H), 1.69–1.61 (m, 4H), 1.57–1.44 (m, 6H), 1.33–1.26 (m, 4H), 1.19 (d, J = 6.3 Hz, 3H), 0.97–0.87 (m, 6H), 0.87 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 173.7, 173.5, 75.2, 70.7, 36.8, 36.7, 36.0, 33.7, 27.1, 25.5, 25.3, 20.1, 18.8, 18.7, 13.83, 13.79, 9.7. HRMS (ESI, m/z): calculated for [M + H]+ C17H33O4 301.2373, found: 301.2374.

3.19. Synthesis of (2R,7S)-nonane-2,7-diyl dibutyrate ((2R,7S)-1)

Using a similar procedure for pheromone (2S,7S)-1, the acylation of (2R,7S)-nonane-2,7-diol ((2R,7S)-9) (135.0 mg, 0.84 mmol, 1.0 equiv.) with butyric anhydride (10) (400.0 mg, 2.53 mmol, 3.0 equiv.) yielded (2R,7S)-nonane-2,7-diyl dibutyrate ((2R,7S)-1) (237.0 mg, 94% yield) as a colorless oil. [α]D25 = −3.97 (c 1.00, CHCl3). 1H NMR (500 MHz, CDCl3) δ 4.92–4.86 (m, 1H), 4.84–4.79 (m, 1H), 2.26 (dt, J = 11.3, 7.4 Hz, 4H), 1.69–1.61 (m, 4H), 1.58–1.46 (m, 6H), 1.35–1.26 (m, 4H), 1.19 (d, J = 6.2 Hz, 3H), 0.97–0.93 (m, 6H), 0.87 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 173.7, 173.5, 75.2, 70.7, 36.8, 36.7, 36.0, 33.7, 27.1, 25.5, 25.3, 20.1, 18.8, 18.7, 13.83, 13.78, 9.7. HRMS (ESI, m/z): calculated for [M + H]+ C17H33O4 301.2373, found: 301.2375.

3.20. Synthesis of (2S,7R)-nonane-2,7-diyl dibutyrate ((2S,7R)-1)

Using a similar procedure for pheromone (2S,7S)-1, the acylation of (2S,7R)-nonane-2,7-diol ((2S,7R)-9) (127.0 mg, 0.79 mmol, 1.0 equiv.) with butyric anhydride (10) (376.0 mg, 2.38 mmol, 3.0 equiv.) yielded (2S,7R)-nonane-2,7-diyl dibutyrate ((2S,7R)-1) (221.0 mg, 93% yield) as a colorless oil. [α]D25 = +3.46 (c 1.97, CHCl3). 1H NMR (500 MHz, CDCl3) δ 4.92–4.86 (m, 1H), 4.84–4.79 (m, 1H), 2.26 (dt, J = 11.3, 7.4 Hz, 4H), 1.69–1.61 (m, 4H), 1.59–1.46 (m, 6H), 1.36–1.24 (m, 4H), 1.19 (d, J = 6.3 Hz, 3H), 0.97–0.93 (m, 6H), 0.87 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 173.7, 173.5, 75.1, 70.7, 36.74, 36.72, 36.0, 33.7, 27.1, 25.5, 25.3, 20.1, 18.8, 18.7, 13.82, 13.77, 9.7. HRMS (ESI, m/z): calculated for [M + H]+ C17H33O4 301.2373, found: 301.2374.

3.21. Synthesis of (2R,7R)-nonane-2,7-diyl dibutyrate ((2R,7R)-1)

Using a similar procedure for pheromone (2S,7S)-1, the acylation of (2R,7R)-nonane-2,7-diol ((2R,7R)-9) (258.0 mg, 1.61 mmol, 1.0 equiv.) with butyric anhydride (10) (764.0 mg, 4.83 mmol, 3.0 equiv.) yielded (2R,7R)-nonane-2,7-diyl dibutyrate ((2R,7R)-1) (458.0 mg, 95% yield) as a colorless oil. [α]D25 = +2.37 (c 1.52, CHCl3). 1H NMR (500 MHz, CDCl3) δ 4.92–4.86 (m, 1H), 4.84–4.79 (m, 1H), 2.26 (dt, J = 11.3, 7.4 Hz, 4H), 1.69–1.61 (m, 4H), 1.59–1.44 (m, 6H), 1.32–1.28 (m, 4H), 1.19 (d, J = 6.3 Hz, 3H), 0.97–0.93 (m, 6H), 0.87 (t, J = 7.4 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 173.7, 173.5, 75.2, 70.7, 36.74, 36.72, 36.0, 33.7, 27.1, 25.5, 25.3, 20.1, 18.8, 18.7, 13.83, 13.78, 9.7. HRMS (ESI, m/z): calculated for [M + H]+ C17H33O4 301.2373, found: 301.2366.

4. Conclusions

In summary, we have conducted a new and efficient synthesis of the sex pheromone of S. mosellana and its stereoisomers with overall yields of 59–64%. The key reactions were the ring opening of chiral epoxide with an alkynyllithium and the hydrogenation of a triple bond. Compared with the existing synthetic methods, our approach has the advantages of cheap materials, high total yields and being easily scaled. Furthermore, our synthesis would be useful in integrated pest management programs for the orange wheat blossom midge.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules30030671/s1, Figures S1–S40 and Table S1. The 1H NMR and 13C NMR spectra for all the synthetic compounds, and comparison of NMR Data between the precious [20] and current synthesized (2S,7S)-1.

Author Contributions

Conceptualization, J.Z.; Methodology, J.W., X.L. and Y.Z.; Writing—review & editing, Q.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the National Key Technology Research and Development Program of China (No. 2023YFD1800900).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this article are available in the Supplementary Materials.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Zhang, G.; Meng, L.; Chen, R.; Wang, W.; Jing, X.; Zhu-Salzman, K.; Cheng, W. Characterization of three glutathione S-transferases potentially associated with adaptation of the wheat blossom midge Sitodiplosis mosellana to host plant defense. Pest Manage. Sci. 2024, 80, 885. [Google Scholar] [CrossRef] [PubMed]
  2. Weeraddana, C.D.S.; Wijesundara, R.; Hillier, W.; Swanburg, T.; Hillier, N.K.; Wang, H.V.; Faraone, N.; Wolfe, S.; McCartney, C.; Wist, T.; et al. Volatile organic compounds mediate host selection of wheat midge, Sitodiplosis mosellana (Gehin) (Diptera: Cecidomyiidae) between preanthesis and postanthesis stages of wheat. J. Chem. Ecol. 2024, 50, 237. [Google Scholar] [CrossRef] [PubMed]
  3. Mingeot, D.; Chavalle, S.; Buhl, P.N.; Sonet, G.; Dubois, B.; Hautier, L. Molecular methods for the detection and identification of parasitoids within larval wheat midges. Sci. Rep. 2024, 14, 27770. [Google Scholar] [CrossRef] [PubMed]
  4. Huang, Q.; Han, X.; Zhang, G.; Zhu-Salzman, K.; Cheng, W. Plant volatiles mediate host selection of Sitodiplosis mosellana (Diptera: Cecidomyiidae) among wheat varieties. J. Agric. Food Chem. 2022, 70, 10466. [Google Scholar] [CrossRef]
  5. Ding, H.; Lamb, R.J. Oviposition and larval establishment of Sitodiplosis mosellana (Diptera: Cecidomyiidae) on wheat (Gramineae) at different growth stages. Can. Entomol. 1999, 131, 475. [Google Scholar] [CrossRef]
  6. Echegaray, E.R.; Barbour, C.R.; Talbert, L.; Stougaard, R.N. Evaluation of Sitodiplosis mosellana (Diptera: Cecidomyiidae) infestation and relationship with agronomic traits in selected spring wheat cultivars in northwestern Montana, United States of America. Can. Entomol. 2018, 150, 675. [Google Scholar] [CrossRef]
  7. Dufton, S.V.; Jorgensen, A.M.; Olfert, O.O.; Otani, J.K. Sitodiplosis mosellana (Gehin), orange wheat blossom midge/Cecidomyie du blé (Diptera: Cecidomyiidae). In Biological Control Programmes in Canada, 2013–2023; Vankosky, M.A., Martel, V., Eds.; CABI: Wallingford, UK, 2024; Volume 6, p. 359. [Google Scholar]
  8. Shrestha, G.; Reddy, G.V.P. Field efficacy of insect pathogen, botanical, and jasmonic acid for the management of wheat midge Sitodiplosis mosellana and the impact on adult parasitoid Macroglenes penetrans populations in spring wheat. Insect Sci. 2019, 26, 523. [Google Scholar] [CrossRef]
  9. El-Wakeil, N.E.; Abdel-Moniem, A.S.H.; Gaafar, N.; Volkmar, C. Effectiveness of some insecticides on wheat blossom midges in winter wheat. Gesunde Pflanz. 2013, 65, 7. [Google Scholar] [CrossRef]
  10. Dufton, S.V.; Olfert, O.O.; Laird, R.A.; Floate, K.D.; Ge, X.; Otani, J.K. A global review of orange wheat blossom midge, Sitodiplosis mosellana (Gehin) (Diptera: Cecidomyiidae), and integrated pest management strategies for its management. Can. Entomo. 2022, 154, e30. [Google Scholar] [CrossRef]
  11. Chavalle, S.; Jacquemin, G.; De Proft, M. Assessing cultivar resistance to Sitodiplosis mosellana (Gehin) (Diptera: Cecidomyiidae) using a phenotyping method under semi-field conditions. J. Appl. Entomol. 2017, 141, 780. [Google Scholar] [CrossRef]
  12. Kumar, S.; Burt, A.; Green, D.; Humphreys, G.; McCallum, B.; Fetch, T.; Menzies, J.; Aboukhaddour, R.; Henriquez, M.A. AAC darby Canada western red spring wheat. Can. J. Plant Sci. 2024. [Google Scholar] [CrossRef]
  13. Rizvi, S.A.H.; George, J.; Reddy, G.V.P.; Zeng, X.; Guerrero, A. Latest developments in insect sex pheromone research and its application in agricultural pest management. Insects 2021, 12, 484. [Google Scholar] [CrossRef] [PubMed]
  14. Souza, J.P.A.; Bandeira, P.T.; Bergmann, J.; Zarbin, P.H.G. Recent advances in the synthesis of insect pheromones: An overview from 2013 to 2022. Nat. Prod. Rep. 2023, 40, 866. [Google Scholar] [CrossRef]
  15. Gries, R.; Gries, G.; Khaskin, G.; King, S.; Olfert, O.; Kaminski, L.-A.; Lamb, R.; Bennett, R. Sex pheromone of orange wheat blossom midge, Sitodiplosis mosellana. Naturwissenschaften 2000, 87, 450. [Google Scholar] [CrossRef] [PubMed]
  16. Chavalle, S.; Censier, F.; Gomez, G.S.M.Y.; De Proft, M. Effect of trap type and height in monitoring the orange wheat blossom midge, Sitodiplosis mosellana (Gain) (Diptera: Cecidomyiidae) and its parasitoid, Macroglenes penetrans (Kirby) (Hymenoptera: Pteromalidae). Crop Prot. 2019, 116, 101. [Google Scholar] [CrossRef]
  17. Senevirathna, K.M.; Guelly, K.N.; Mori, B.A. Management of the orange blossom wheat midge, Sitodiplosis mosellana, in western Canada. Plant Health Cases 2023, 2023, phcs20230002. [Google Scholar] [CrossRef]
  18. Li, C.; Wu, Y.; Yin, X.; Gong, Z.; Xing, H.; Miao, J.; Wang, S.; Liu, J.; Na, R.; Li, Q. Modular synthesis of the pheromone (2S, 7S)-2, 7-nonanediyl dibutyrate and its racemate and their field efficacy to control orange wheat blossom midge, Sitodiplosis mosellana (Géhin)(Diptera: Cecidomyiidae). Pest Manag. Sci. 2023, 79, 97. [Google Scholar] [CrossRef]
  19. Na, R.; Liu, J.; Song, N.; Yin, X.; Lu, S.; Wu, Y.; Tang, Q.; Li, W.; Liu, B.; Wang, C. Synthesis of Red Wheat Blossom Midge Sex Pheromone Precursor Compound and Red Wheat Blossom Midge Sex Pheromone. CN Patent 105085168, 29 March 2017. [Google Scholar]
  20. Hooper, A.M.; Dufour, S.; Willaert, S.; Pouvreau, S.; Pickett, J.A. Synthesis of (2S,7S)-dibutyroxynonane, the sex pheromone of the orange wheat blossom midge, Sitodiplosis mosellana (Gehin) (Diptera: Cecidomyiidae), by diastereoselective silicon-tethered ring-closing metathesis. Tetrahedron Lett. 2007, 48, 5991. [Google Scholar] [CrossRef]
  21. Bruce, T.J.; Hooper, A.M.; Ireland, L.; Jones, O.T.; Martin, J.L.; Smart, L.E.; Oakley, J.; Wadhams, L.J. Development of a pheromone trap monitoring system for orange wheat blossom midge, Sitodiplosis mosellana, in the UK. Pest Manag. Sci. 2007, 63, 49. [Google Scholar] [CrossRef]
  22. Hernandez-Torres, G.; Mateo, J.; Urbano, A.; Carreno, M.C. The shortest (four-step) total synthesis of the eight-membered cyclic ether racemic- and (-)-cis-lauthisan. Eur. J. Org. Chem. 2013, 2013, 6259. [Google Scholar] [CrossRef]
  23. Thiraporn, A.; Rukachaisirikul, V.; Iawsipo, P.; Somwang, T.; Tadpetch, K. Total synthesis and cytotoxic activity of 5′-hydroxyzearalenone and 5′β-hydroxyzearalenone. Eur. J. Org. Chem. 2017, 2017, 7133. [Google Scholar] [CrossRef]
  24. Abad, J.-L.; Camps, F.; Fabrias, G. Substrate-dependent stereochemical course of the (Z)-13-desaturation catalyzed by the processionary moth multifunctional desaturase. J. Am. Chem. Soc. 2007, 129, 15007. [Google Scholar] [CrossRef]
  25. Yan, F.; Moon, S.-J.; Liu, P.; Zhao, Z.; Lipscomb, J.D.; Liu, A.; Liu, H.-w. Determination of the substrate binding mode to the active site iron of (S)-2-hydroxypropylphosphonic acid epoxidase using 17O-enriched substrates and substrate analogues. Biochemistry 2007, 46, 12628. [Google Scholar] [CrossRef] [PubMed]
  26. Bhuniya, R.; Mahapatra, T.; Nanda, S. Klebsiellapneumoniae (NBRC 3319) mediated asymmetric reduction of α-substituted β-oxo esters and its application to the enantioiselective synthesis of small-ring carbocycle derivatives. Eur. J. Org. Chem. 2012, 2012, 1597. [Google Scholar] [CrossRef]
  27. Pettersson, M.; Johnson, D.S.; Humphrey, J.M.; am Ende, C.W.; Butler, T.W.; Dorff, P.H.; Efremov, I.V.; Evrard, E.; Green, M.E.; Helal, C.J.; et al. Discovery of clinical candidate PF-06648671: A potent γ-secretase modulator for the treatment of Alzheimer’s disease. J. Med. Chem. 2024, 67, 10248. [Google Scholar] [CrossRef] [PubMed]
  28. Bucknam, A.R.; Micalizio, G.C. Asymmetric de novo synthesis of a cucurbitane triterpenoid: Total synthesis of octanorcucurbitacin B. J. Am. Chem. Soc. 2022, 144, 8493. [Google Scholar] [CrossRef] [PubMed]
  29. Geerdink, D.; Horst, B.T.; Lepore, M.; Mori, L.; Puzo, G.; Hirsch, A.K.H.; Gilleron, M.; de Libero, G.; Minnaard, A.J. Total synthesis, stereochemical elucidation and biological evaluation of Ac2SGL; a 1,3-methyl branched sulfoglycolipid from Mycobacterium tuberculosis. Chem. Sci. 2013, 4, 709. [Google Scholar] [CrossRef]
  30. Madasu, M.; Mohapatra, D.K. Total synthesis of okaspirodiol. ChemistrySelect 2023, 8, e202300352. [Google Scholar] [CrossRef]
  31. Takahashi, N.; Hayashi, H.; Poznaks, V.; Kakeya, H. Total synthesis of verucopeptin, an inhibitor of hypoxia-inducible factor 1 (HIF-1). Chem. Commun. 2019, 55, 11956. [Google Scholar] [CrossRef]
  32. Chen, D.; Evans, P.A. A concise, efficient and scalable total synthesis of thapsigargin and nortrilobolide from (R)-(-)-carvone. J. Am. Chem. Soc. 2017, 139, 6046. [Google Scholar] [CrossRef] [PubMed]
  33. Zheng, J.F.; Lan, H.Q.; Yang, R.F.; Peng, Q.L.; Xiao, Z.H.; Tuo, S.C.; Hu, K.Z.; Xiang, Y.G.; Wei, Z.; Zhang, Z.; et al. Asymmetric syntheses of the sex pheromones of pine sawflies, their homologs and stereoisomers. Helv. Chim. Acta 2012, 95, 1799. [Google Scholar] [CrossRef]
Molecules 30 00671 g001
Figure 1. Sex pheromone of S. mosellana and its stereoisomers.
Figure 1. Sex pheromone of S. mosellana and its stereoisomers.
Molecules 30 00671 g001
Molecules 30 00671 sch001
Scheme 1. Retrosynthetic analysis of sex pheromone of S. mosellana (2S,7S)-1.
Scheme 1. Retrosynthetic analysis of sex pheromone of S. mosellana (2S,7S)-1.
Molecules 30 00671 sch001
Molecules 30 00671 sch002
Scheme 2. Synthesis of chiral TBDPS ethers (S)- and (R)-5.
Scheme 2. Synthesis of chiral TBDPS ethers (S)- and (R)-5.
Molecules 30 00671 sch002
Molecules 30 00671 sch003
Scheme 3. Synthesis of sex pheromone of S. mosellana.
Scheme 3. Synthesis of sex pheromone of S. mosellana.
Molecules 30 00671 sch003
Molecules 30 00671 sch004
Scheme 4. Synthesis of stereoisomers of S. mosellana sex pheromone.
Scheme 4. Synthesis of stereoisomers of S. mosellana sex pheromone.
Molecules 30 00671 sch004
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Wang, J.; Li, X.; Zhou, Y.; Bian, Q.; Zhong, J. Enantioselective Synthesis of the Sex Pheromone of Sitodiplosis mosellana (Géhin) and Its Stereoisomers. Molecules 2025, 30, 671. https://doi.org/10.3390/molecules30030671

AMA Style

Wang J, Li X, Zhou Y, Bian Q, Zhong J. Enantioselective Synthesis of the Sex Pheromone of Sitodiplosis mosellana (Géhin) and Its Stereoisomers. Molecules. 2025; 30(3):671. https://doi.org/10.3390/molecules30030671

Chicago/Turabian Style

Wang, Jianan, Xiaoyang Li, Yun Zhou, Qinghua Bian, and Jiangchun Zhong. 2025. "Enantioselective Synthesis of the Sex Pheromone of Sitodiplosis mosellana (Géhin) and Its Stereoisomers" Molecules 30, no. 3: 671. https://doi.org/10.3390/molecules30030671

APA Style

Wang, J., Li, X., Zhou, Y., Bian, Q., & Zhong, J. (2025). Enantioselective Synthesis of the Sex Pheromone of Sitodiplosis mosellana (Géhin) and Its Stereoisomers. Molecules, 30(3), 671. https://doi.org/10.3390/molecules30030671

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