کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
49726 | 46763 | 2015 | 5 صفحه PDF | دانلود رایگان |
• An efficient chemoenzymatic route for the production of gabapentin was developed.
• 1-Cyanocyclohexaneacetic acid was synthesized by a greatly improved nitrilase.
• A feasible procedure for producing the regioselective nitrilase was demonstrated.
• Direct hydrogenation of 1-cyanocyclohexaneacetic acid was performed successfully.
An efficient chemoenzymatic process is devised for synthesizing high-purity gabapentin. 1-Cyanocyclohexaneacetic acid was first produced in 0.94 M from 1.0 M 1-cyanocycloalkaneacetonitrile by a greatly improved nitrilase from Acidovorax facilis ZJB09122, resulting in a commercially attractive bioprocess with an outstanding space-time yield of 461 g/L/day. The resulting aqueous 1-cyanocycloalkaneacetic acid was then directly converted to 2-azaspiro [4.5] decan-3-one without further purification in subsequent hydrogenation by Raney-nickel, followed by simple chemical steps to afford gabapentin in high purity and 77.3% overall yield from 1-cyanocyclohexylacetonitrile. The simplicity of the process makes this new pathway suitable for large-scale preparation.
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Journal: Catalysis Communications - Volume 66, 5 June 2015, Pages 121–125