Synthesis of Azedarachol and 2α,3α,20R-Trihydroxypregnane-16β-methacrylate

doi:10.6023/cjoc202203040

Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (8): 2521-2526.DOI: 10.6023/cjoc202203040 Previous Articles Next Articles

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苦楝甾醇及2α,3α,20R-三羟基孕甾-16β-甲基丙烯酸酯的合成

高冉^a^,^*(), 田伟生^b^,^*()

a 淮北师范大学化学与材料科学学院安徽淮北 235000
b 中国科学院上海有机化学研究所天然产物有机合成化学重点实验室上海 200032

收稿日期:2022-03-21 修回日期:2022-04-27 发布日期:2022-05-06
通讯作者: 高冉, 田伟生

Synthesis of Azedarachol and 2α,3α,20R-Trihydroxypregnane-16β-methacrylate

Ran Gao^a(), Weisheng Tian^b()

a School of Chemistry and Materials Science, Huaibei Normal University, Huaibei, Anhui 235000
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences, Shanghai 200032

Received:2022-03-21 Revised:2022-04-27 Published:2022-05-06
Contact: Ran Gao, Weisheng Tian

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Abstract

Azedarachol (3) and 2α,3α,20R-trihydroxypregnane-16β-methacrylate (4) were isolated from the root bark of Melia azedarach L. in 1984 by Nakatani and coworkers. Azedarachol (3) shows excellent antifeedant activity against the larvae of Ajrotis sejetum Denis at the concentration of 500 μg/mL, and 2α,3α,20R-trihydroxypregnane-16β-methacrylate (4) inhibits the HGC27 tumor cells with an IC₅₀ value of (11.3±0.5) μg/mL. The noteworthy activities and the high oxidation state structure as well as the scarce of sample suppling in nature resources have attracted considerable attention from the synthetic community. Herein the synthesis of these two natural products from preganetriol (2) is reported. The route features a stereoselective inversion at C(20) and a substrate controlled dihydroxylation of C(23) double bond. 3 and 4 were obtained in an overall yields of 6% (11 steps) and 7.5% (11 steps), respectively.

Key words: preganetriol, azedarachol, 2α,3α,20R-trihydroxypregnane-16β-methacrylate, total synthesis, natural products

Cite this article

Ran Gao, Weisheng Tian. Synthesis of Azedarachol and 2α,3α,20R-Trihydroxypregnane-16β-methacrylate[J]. Chinese Journal of Organic Chemistry, 2022, 42(8): 2521-2526.

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Fig. & Tab. 4

Figure 1. Structures of tigogenin (1), preganetriol (2), azedarachol (3) and 2α,3α,20R-trihydroxypregnane-16β-methacrylate (4)

Scheme 1. Retrosynthetic analysis of 3 and 4

Scheme 2. Preparation of 11

Scheme 3. Synthesis of azedarachol (3) and 2α,3α,20R-trihydroxypregnane-16β-methacrylate (4)

References 6

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[6]	Compound 10/11 cannot be separated by column chromatography, and the proportion of oxidation product 10a/11a obtained by further oxidation is 74%/11%.

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苦楝甾醇及2α,3α,20R-三羟基孕甾-16β-甲基丙烯酸酯的合成

Synthesis of Azedarachol and 2α,3α,20R-Trihydroxypregnane-16β-methacrylate

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