Asymmetric synthesis of (-)-fosfomycin and its trans-(1S,2S)-diastereomer using a biocatalytic reduction as the key step

作者：Marocco Christian P; Davis Erik V; Finnell Julie E; Phung Hoang Nguyen; Mateer Scott C; Ghiviriga Ion; Padgett Clifford W; Feske Brent D^*

来源：Tetrahedron: Asymmetry , 2011, 22(18-19): 1784-1789.

DOI：10.1016/j.tetasy.2011.10.009

Fosfomycin is a gram positive and gram negative antibiotic that contains an asymmetric epoxide. An enzyme library was screened for its ability to reduce dimethyl(1-chloro-2-oxopropyl)phosphonate to the corresponding asymmetric chlorohydrin. Homology models were built in MOE, which were shown to accurately model the enzyme-substrate complex displaying the stereoselectivity that we observed. Two enzymes, YDR368w and YHR104w, were chosen for the scale up and synthesis of fosfomycin and its trans-(1S,2S)-diastereomer.

• 出版日期2011-10-15