Nitrile biotransformations for the synthesis of highly enantioenriched beta-hydroxy and beta-amino acid and amide derivatives: a general and simple but powerful and efficient benzyl protection strategy to increase enantioselectivity of the amidase.
Biotransformations of a number of racemic beta-hydroxy and beta-amino nitrile derivatives were studied using Rhodococcus erythropolis AJ270, the nitrile hydratase and amidase-containing microbial whole cell catalyst, under very mild conditions. The overall enantioselectivity of nitrile biotransformations was governed predominantly by the amidase whose enantioselectivity was switched on remarkably by an O- and a N-benzyl protection group of the substrates. While biotransformations of beta-hydroxy and beta-amino alkanenitriles gave low yields of amide and acid products of very low enantiomeric purity, introduction of a simple benzyl protection group on the beta-hydroxy and beta-amino of nitrile substrates led to the formation of highly enantioenriched beta-benzyloxy and beta-benzylamino amides and acids in almost quantitative yield. The easy protection and deprotection operations, high chemical yield, and excellent enantioselectivity render the nitrile biotransformation a useful protocol in the synthesis of enantiopure beta-hydroxy and beta-amino acids.
Ma
Da-You
DY
Beijing National Laboratory for Molecular Sciences, Laboratory of Chemical Biology, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Wang
De-Xian
DX
Pan
Jie
J
Huang
Zhi-Tang
ZT
Wang
Mei-Xiang
MX
D000577:Amides / Q000737:chemistry*; D000581:Amidohydrolases / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D009570:Nitriles / Q000737:chemistry*; D012240:Rhodococcus / Q000201:enzymology; D013237:Stereoisomerism
D000577:Amides; D000596:Amino Acids; D009570:Nitriles; D000581:Amidohydrolases; C019665:amidase