Asymmetric synthesis of 1,3-oxathiolan-5-one derivatives through dynamic covalent kinetic resolution

TETRAHEDRON

卷:70

Article

Zhang, Yan¹  Schaufelberger, Fredrik¹  Sakulsombat, Morakot¹  Liu, Chelsea¹  Ramstrom, Olof¹ 

[1] KTH Royal Inst Technol, Dept Chem, S-10044 Stockholm, Sweden

关键词: Dynamic chemistry;    Dynamic kinetic resolution;    Enzyme catalysis;    Hemithioacetal formation;    Lactonization;    Nucleoside analogs;   

DOI  :  10.1016/j.tet.2014.03.059

来源: Elsevier

【 摘 要 】

The asymmetric synthesis of 1,3-oxathiolan-5-one derivatives through an enzyme-catalyzed, dynamic covalent kinetic resolution strategy is presented. Dynamic hemithioacetal formation combined with intramolecular, lipase-catalyzed lactonization resulted in good conversions with moderate to good enantiomeric excess (ee) for the final products. The process was evaluated for different lipase preparations, solvents, bases, and reaction temperatures, where lipase B from Candida antarctica (CAL-B) proved most efficient. The substrate scope was furthermore explored for a range of aldehyde structures, together with the potential access to nucleoside analog inhibitor core structures. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.

【 授权许可】

Free