Journal
ORGANIC PROCESS RESEARCH & DEVELOPMENT
Volume 15, Issue 1, Pages 241-248Publisher
AMER CHEMICAL SOC
DOI: 10.1021/op1001534
Keywords
-
Categories
Ask authors/readers for more resources
The (S)-amino acid, (S)-2-amino-3-(6-o-tolylpyridin-3-yl)propanoic acid (3), is a key intermediate needed for synthesis of an antidiabetic drug candidate. Three enzymatic routes to 3 were explored. (S)-Amino acid 3 could be prepared in 73% isolated yield with 99.9% ee from racemic amino acid 1 using (R)-amino acid oxidase from Trigonopsis variabilis expressed in Escherichia coli in combination with an (S)-aminotransferase using (S)-aspartate as amino donor. The (S)-aminotransferase was purified from a soil organism identified as Burkholderia sp. and cloned and expressed in E. coli. (S)-Amino acid 3 with 100% ee was also prepared in 68% solution yield and 54% isolated yield from 1 using recombinant (R)-amino acid oxidase from T. variabilis and an (S)-amino acid dehydrogenase from Sporosarcina ureae. The cofactor NADH required for the reductive amination reaction was regenerated using formate and formate dehydrogenase. The chemoenzymatic dynamic resolution of 1 by (R)-selective oxidation with Celite-immobilized (R)amino acid oxidase in combination with chemical imine reduction using borane-ammonia complex gave an 81% solution yield and 68% isolated yield of 3 with 100% ee.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available