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

Maryam Bashir; Muhammad Arshad; Robina Begum; Varinder k. Aggarwal

doi:10.1021/acs.orglett.3c01286

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

Maryam Bashir, Muhammad Arshad^*, Robina Begum, Varinder k. Aggarwal^*

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

4 Citations (Scopus)

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.

Original language	English
Pages (from-to)	4281–4285
Number of pages	5
Journal	Organic Letters
Volume	25
Issue number	23
Early online date	7 Jun 2023
DOIs	https://doi.org/10.1021/acs.orglett.3c01286
Publication status	Published - 16 Jun 2023

Bibliographical note

Funding Information:
The authors thank Commonwealth Commission UK under the Split-site Ph.D. Programme (2021-2022) and the Higher Education Commission (HEC), Pakistan, under IRSIP (2022) for generous financial support.

Publisher Copyright:
© 2023 American Chemical Society. All rights reserved.

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

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.",

author = "Maryam Bashir and Muhammad Arshad and Robina Begum and Aggarwal, {Varinder k.}",

note = "Funding Information: The authors thank Commonwealth Commission UK under the Split-site Ph.D. Programme (2021-2022) and the Higher Education Commission (HEC), Pakistan, under IRSIP (2022) for generous financial support. Publisher Copyright: {\textcopyright} 2023 American Chemical Society. All rights reserved.",

year = "2023",

month = jun,

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doi = "10.1021/acs.orglett.3c01286",

language = "English",

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journal = "Organic Letters",

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T1 - Application of Enantioselective Sulfur Ylide Epoxidation to a Short Asymmetric Synthesis of Bedaquiline, a Potent Anti-Tuberculosis Drug

AU - Bashir, Maryam

AU - Arshad, Muhammad

AU - Begum, Robina

AU - Aggarwal, Varinder k.

N1 - Funding Information: The authors thank Commonwealth Commission UK under the Split-site Ph.D. Programme (2021-2022) and the Higher Education Commission (HEC), Pakistan, under IRSIP (2022) for generous financial support. Publisher Copyright: © 2023 American Chemical Society. All rights reserved.

PY - 2023/6/16

Y1 - 2023/6/16

N2 - 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.

AB - 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.

U2 - 10.1021/acs.orglett.3c01286

DO - 10.1021/acs.orglett.3c01286

M3 - Article (Academic Journal)

C2 - 37284829

SN - 1523-7060

VL - 25

SP - 4281

EP - 4285

JO - Organic Letters

JF - Organic Letters

IS - 23

ER -

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

Abstract

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