ENZYMATIC-HYDROLYSIS OF METHYL 3,3-DIFLUORO-2-AMINO ESTERS - SYNTHESIS OF D-3,3-DIFLUORO-2-AMINO AND L-3,3-DIFLUORO-2-AMINO ACIDS AND THEIR DERIVATIVES

The hydrolysis of methyl D,L-3,3-difluorophenyl alanate (la) and methyl D,L-3,3-difluoro-2-aminobutanoate (Ib) and their N-acetyl derivatives 2a and 2b by subtilisin has been studied. All derivatives examined were enzymatically resolved to separable mixtures of the corresponding 3,3-difluoro-L-amino acids (3a and 3b) or N-acetylamino acids (5a and 5b) and the unchanged 3,3-difluoro-D-amino esters (4a and 4b) or N-acetylamino esters (6a and 6b). Acidic hydrolysis of methyl 3,3-difluoro-D-phenyl alanate (4a) or its N-acetyl derivative 6a led to 3,3-difluoro-D-phenyl alanime (8a), In the same manner, L- and D-2-amino-3,3-difluorobutanoic acids 7b and 8b were prepared starting from 5b and 6b, Optical purity and enantiomeric excess were determined by GC analysis of the N-acetyl esters and by NMR analysis determined in the presence of Eu(tfc)3, By these methods, unchanged methyl 3,3-difluoro-D-amino ester derivatives showed an ee of greater than or equal to 90% while L-amino acids were estimated to have greater than or equal to 95% ee.