Green Synthesis and Catalysis (Aug 2021)

Enantioselective biocatalytic desymmetrization for synthesis of enantiopure cis-3,4-disubstituted pyrrolidines

  • Hui-Juan Hu,
  • Qi-Qiang Wang,
  • De-Xian Wang,
  • Yu-Fei Ao

Journal volume & issue
Vol. 2, no. 3
pp. 324 – 327

Abstract

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A versatile biocatalytic desymmetric method for efficiently accessing enantiopure cis-3,4-disubstituted pyrrolidines was developed. Catalyzed by amidase-containing E. coli whole cells, a series of meso pyrrolidine-2,5-dicarboxamides were hydrolyzed to obtain 4-carbamoylpyrrolidine-3-carboxylic acid derivatives in 47%–95% yields and 62% ∼ >99.5% ee values under mild condition. The catalytic efficiency and enantioselectivity are related to the substituents in the phenyl ring. The enzyme-substrate binding mode is established and the high enantioselectivity of amidase is revealed by MD simulations. The improvement of biocatalytic efficiency has been preliminarily explored through protein engineering.

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