Enzymatic resolution of Cα-fluoroalkyl substituted amino acids

A methodology for the enzymatic resolution of sterically constrained C-alpha-fluoroalkyl substituted amino acids has been developed. Racemic H-(alphaTfm)Ala-NH2, H-(alphaCF(2)Cl)Ala-NH2 and H-(alphaCF(2)Br)Ala-NH2 was separated with very high enantio-selectivity (E >200) into their enantiomers using amidase from Mycobacterium neoaurum yielding the corresponding (R)-acids. Furthermore, the first example of an enzymatic resolution of a C-alpha-fluoroalkyl substituted Phe derivative has been established using amidase from Ochrobactrum anthropi. (C) 2004 Published by Elsevier Ltd.