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

The success in the optirnized synthesis of allryl and hydroxy glutamic acid
derivatives provides the opportunity to expand the methodology into other aspects of
glutamic acid chemistry. However, the synthesis of the filly protected glutamate
derivative 4.69, although cumntly optirnized, would be advantageous if column
purification could be avoided. The crystalline derivative is stable making it particularly
amenable for use as a generai synthon.
Confirmation of the model predicting the stereochernistry of addition of various
electrophiles with glutamic acid could be achieved by di-N-protection. The N-Li bond,
thus removeci, could no longer participate in chelation, which is cntical in the proposed
model in section 4.2.10. Replacing the OB0 ester protecting group with the AB0 ester
protecting group as described by Wipf et aL2 and thus increasing the sue of the directing
group may have a beneficiai effet on stereoselectivity.
The successful synthesis of 2S,4R-arninogluiamic acid via the nucleophilic
addition of azide illustrates the synthetic utility of the activated hydtonyl derivative of
glutamic acid. Numerous other nucleophilic additions may be envisioned, providing
access to 2S,4R derivatives of glutamic acid and hence complementarity to the synthesis
of 2S94S substituted glutamates described in ihis thesis. The y-bromoglutamate derivative
should also be investigated as a y-cationic glutamate denvative.
Preliminary results indicate the Claisen condensation described in section 4.2.8 to
be partieularly prornising. Current methods for the synthesis of substituted indolizidines
in a stereoselective manner are severely lacking. Decarboxylation of the glutamate dimer
4.117 to the ketone 4.118 would provide the opportunity for 1,3-stereochemical induction
in 4.118. This may allow for the stereoselective introduction of various substituents into