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

A general method for the synthesis of a wide variety of SS,U 'substituted
glutamates has been developed w ith diastereoselectivities generall y >95: 5 (2S94S;2S,4R).
This methodology represents a significant step in the synthesis of y-substituted glutamic
acids due to its hi& selectivity and flexibility since a wide variety of substituents rnay be
incorporated. Overail yield of the fne ysubstituted glutamic acids fiom glutamic acid
4.60 range from 15-33% over six steps. The fully protected glutamate 4.69 is
conveniently crystalline as are a number of the y-substituted derivatives.
The 4-alkyl substitutents are easily generated in high yield (75-846 yield) and
excellent diastereoselectivity (>95:5) with the only contaminant starting material, whic h
may be recovered and recycled.
y-Hydroxyglutamic acid 4.4 is synthesized in good overaii yield (2546) and
excellent diastereomeric purity (~95:s) and is a noteworthy improvement over cumnt
rnethods used to synthesize this amino acid. The synthesis of the two unidentified
dias tereomers of dihydroxyglutamic acid (4.102/4.103) represents a significan t
improvement of current methods in both length and overdl yield. fi-Hydroxyglutamic
acid 4.7 was synthesized in both good yield and high diastereoselectivity, comparable to
other reported methods. Furthermore, crystalline ~S,~S-C~~-G~U(~OH)(OM~)OBO
ester
4.96 provides access to a number of other potential denvatives via functionalization of
the hydroxyl group as illustrated in the synîhesis of the 2S,4R isomer of diaminoglutamic
acid.
Protected 2S,4S-azidoglutamic acid 4.106 was obtained in moderate yield (54%)
but excellent diastereomeric purity (>95:5). Reduction and deprotection gave 2S,4S-