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Title: Synthesis of chiral sulfinate esters by asymmetric condensation
Authors: Zhang, Xin
Ang, Esther Cai Xia
Yang, Ziqi
Kee, Choon Wee
Tan, Choon-Hong
Keywords: Science::Chemistry
Issue Date: 2022
Source: Zhang, X., Ang, E. C. X., Yang, Z., Kee, C. W. & Tan, C. (2022). Synthesis of chiral sulfinate esters by asymmetric condensation. Nature, 604(7905), 298-303.
Project: RG2/20 
Journal: Nature 
Abstract: Achiral sulfur functional groups, such as sulfonamide, sulfone, thiol and thioether, are common in drugs and natural products. By contrast, chiral sulfur functional groups are often neglected as pharmacophores1-3, although sulfoximine, with its unique physicochemical and pharmacokinetic properties4,5, has been recently incorporated into several clinical candidates. Thus, other sulfur stereogenic centres, such as sulfinate ester, sulfinamide, sulfonimidate ester and sulfonimidamide, have started to attract attention. The diversity and complexity of these sulfur stereogenic centres have the potential to expand the chemical space for drug discovery6-10. However, the installation of these structures enantioselectively into drug molecules is highly challenging. Here we report straightforward access to enantioenriched sulfinate esters via asymmetric condensation of prochiral sulfinates and alcohols using pentanidium as an organocatalyst. We successfully coupled a wide range of sulfinates and bioactive alcohols stereoselectively. The initial sulfinates can be prepared from existing sulfone and sulfonamide drugs, and the resulting sulfinate esters are versatile for transformations to diverse chiral sulfur pharmacophores. Through late-stage diversification11,12 of celecoxib and other drug derivatives, we demonstrate the viability of this unified approach towards sulfur stereogenic centres.
ISSN: 0028-0836
DOI: 10.1038/s41586-022-04524-4
Schools: School of Physical and Mathematical Sciences 
Organisations: Institute of Chemical and Engineering Sciences, Singapore
Rights: © 2022 The Author(s), under exclusive licence to Springer Nature Limited. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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