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

Countiess examples exist of the synthesis of unusual a-amino acids from other amino
acid precurs~rs,'~*"~~ but as a whole. general methods for the synthesis of a-amino acids
can be separated into three groups: formylglycine equivalents, alanine p-anion
equivalents and alanine &cation equivalents. The basic chiral a-amino acid synthons are
the alanine p-anion 1.48 and p-cation 1.49 which are generally denved frorn senne,
cysteine, aspartic acid and to a lesser extent from glutamic acid (Scheme 1.22).
Formylglycine, although discussed separately, can be considered an alanine B-cation
equivalent .
1.3.4.1 Formyiglycine Equivalents
Scheme 1.22
The most common formylglycine equivalents are serine aldehydes generally
derived directly from serine. As an obvious choice for the derivatization to other a-
amino acids, serine suffers from a few notable deficiencies that must necessarily be
addressed. Senne is one of the amino acids most prone to racernization and is believed to
involve a plana. carbanion intemediate produced by the rate-determining removal of the
a-proton.' This increased rate is due to the hydroxyl gmup which helps stabilue the
intermediate anion. Furthemore, if the side chain is oxidized to a senne aldehyde,
enolization results in racemization at the a-center. As such, numerous approaches have
been undertaken in order to adbss this issue. Two routes may be employed in the