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

Abstract
Non-proteinacous amino acids are important components of numerous
biologically active compounds. As a consequence, there is much interest in the
development of straightforward routes for their synthesis. A novel strategy for the
synthesis of several classes of non-proteinacous a-amino acids from a variety of a-arnino
acids is presented in this thesis.
A general strategy of protecting the a-carboxyl group of serine. threonine,
aspartic acid and glutamic acid as a cyclic ortho ester (OBO), sufficiently reduces the
acidity of the a-proton to allow the use of a variety of basic reagents minimizing
racemization at the a-proton.
The sidechain hydroxyl group in BodOBO protected senne and threonine is
oxidized to the corresponding aldehyde and ketone without enolization. Grignard and
Reformatsky additions produced predorninantly threo-fl-hydroxy-a-amino acids in good
selectivi ty w i th no racemization. Adaptation of the methodology ont0 the solid phase
also gave threo-P-hydroxy-a-amino acids albeit with some racemization
The addition of various electrophiles to the enolate of N-Cbz-a-OBO-y-methyl
ester glutamic acid gave the 2S,4S stereoisorners with excellent selectivity and good
yield. Alkylation, acylation, Aldol and Claisen reactions and the electrophilic addition of
various heteroatoms is described.
Electrophilic additions to the enolate of N-Cbz-a-OBO-y-rnethyl ester aspartic
acid gave the more dificult to synthesize 2S,3S stereoisomer with varying degrees of
stereoselectivity and yields depending on the electrophile.
The stereochemistry of addition for the enolate chernistry is also explored.
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