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对映选择性硫叶立德环氧化在一种有效的抗结核药物贝达喹啉的不对称短合成中的应用。

Application of Enantioselective Sulfur Ylide Epoxidation to a Short Asymmetric Synthesis of Bedaquiline, a Potent Anti-Tuberculosis Drug.

机构信息

School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, U.K.

Centre for Organic Chemistry, School of Chemistry, University of the Punjab, Lahore 54590, Pakistan.

出版信息

Org Lett. 2023 Jun 16;25(23):4281-4285. doi: 10.1021/acs.orglett.3c01286. Epub 2023 Jun 7.

DOI:10.1021/acs.orglett.3c01286
PMID:37284829
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10278180/
Abstract

A highly selective asymmetric synthesis of a potent anti-TB drug (-)-bedaquiline is accomplished using sulfur ylide asymmetric epoxidation, employing (+)-isothiocineole as an inexpensive and readily available chiral sulfide. Excellent enantioselectivity (er 96:4) and diastereoselectivity (dr 90:10) were obtained for the construction of the key diaryl epoxide, which was subsequently subjected to a highly regioselective ring opening (96:4). The synthesis was completed in nine steps starting from commercially available aldehyde in 8% overall yield.

摘要

使用硫叶立德不对称环氧化反应，以（+）-异硫氰酸松油醇作为廉价易得的手性硫化物，高效高对映选择性（er 96:4）和非对映选择性（dr 90:10）地合成了一种有效的抗结核药物（-）-贝达喹啉。关键的二芳基环氧化物随后进行了高度区域选择性开环（96:4）。该合成从商业可得的醛出发，经 9 步反应以 8%的总收率完成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/543f515e2449/ol3c01286_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/766fcbb22570/ol3c01286_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/766867c922ea/ol3c01286_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/89182bd59165/ol3c01286_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/c3208bfe9bcd/ol3c01286_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/543f515e2449/ol3c01286_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/766fcbb22570/ol3c01286_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/766867c922ea/ol3c01286_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/89182bd59165/ol3c01286_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/c3208bfe9bcd/ol3c01286_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/10278180/543f515e2449/ol3c01286_0005.jpg

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