Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

enantiomers of methyl ketoglutarate 4.22 (R = Me) was observecl since a 1: 1 mixture of
2S:4R and 2R:4S rnethylglutarnic acid was isolated.fz
In 1987, Bolte et al. reporteci the large-scale synthesis of y-hydroxy-L-glutank
acid by the transamination of cysteine sulfinic acid and y-hydroxy-a-ketoglutarate
cataiyzed by glutamic oxalacetic transaminase (E.C. 2-61. l)." In 1993, the sarne group
descnbed the synthesis of methyl and ethyl y-substituted glutarnic acid and in 1999 the
synthesis of n-propyl-y-giutamate (Scheme 4.6, cight-hand side). Al1 three alkyl
substituents gave 4: 1 ratios of 2S:4R to 234s palkylglutamates while equal amounts of
threo and erythro y-hydroxyglutarnate were is~lated.~
Kokuryo et al.35 used a combination of recrystalüzation and porcine kidney
arninoacylase (EC. 3 S. 1.14) to prepare enantiomericall y pure L-erythro and L-threo-4-
fluoroglutamic acid in poor yield from a racemic mixture of 4-fîuoroglutamate 4.12
synthesized via Hudlicky's methoci.'
EtOH CH3CH0
Scheme 4.6
GDH = Glutamate dehydmgenase
YADH = Yeast alcohd dehydrogenase
GOT = Glutamic oxalacetic transaminase
HO&
,-y+q-
Cysteine O HO&
sulfinic
acid SO. + A cozH R = Me. Et.
nPr, OH