Synthesis of chiral sulfinate esters by asymmetric condensation

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Synthesis of chiral sulfinate esters by asymmetric condensation
Title:
Synthesis of chiral sulfinate esters by asymmetric condensation
Journal Title:
Nature
Publication Date:
14 February 2022
Citation:
Zhang, X., Ang, E. C. X., Yang, Z., Kee, C. W., & Tan, C.-H. (2022). Synthesis of chiral sulfinate esters by asymmetric condensation. Nature, 604(7905), 298–303. https://doi.org/10.1038/s41586-022-04524-4
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 pharmacophores although sulfoximine, with its unique physicochemical and pharmacokinetic properties, 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 discovery. 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 diversification of celecoxib and other drug derivatives, we demonstrate the viability of this unified approach towards sulfur stereogenic centres.
License type:
Publisher Copyright
Funding Info:
This research / project is supported by the Nanyang Technological University - Tier 1 grant
Grant Reference no. : RG2/20

This research / project is supported by the Ministry of Education, Singapore - Academic Research Fund Tier 2
Grant Reference no. : MOE2019-T2-1-091
Description:
This version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1038/s41586-022-04524-4
ISSN:
1476-4687
0028-0836
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