Ai. Ayi et al., 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 THEIRDERIVATIVES, Journal of fluorine chemistry, 73(2), 1995, pp. 165-169
The hydrolysis of methyl D,L-3,3-difluorophenyl alanate (la) and methy
l D,L-3,3-difluoro-2-aminobutanoate (Ib) and their N-acetyl derivative
s 2a and 2b by subtilisin has been studied. All derivatives examined w
ere 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-ace
tylamino 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-difluor
o-D-phenyl alanime (8a), In the same manner, L- and D-2-amino-3,3-difl
uorobutanoic acids 7b and 8b were prepared starting from 5b and 6b, Op
tical 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 est
er derivatives showed an ee of greater than or equal to 90% while L-am
ino acids were estimated to have greater than or equal to 95% ee.