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

formation of serine aldehydes; direct oxidation of the side chah to the aldehyde without
altering the oxidation state of the carboxylic acid group, and reduction of the acid to the
aldehyde and subsequently oxidizing the side chah to the carboxylic acid in order to
regenerate the a-amino acid These methods include the use of protecting groups that
reduce or mask the ability of the a-proton to racernize.
The most important serine-derived aldehydes designed for the synthesis of a-
arnino acids are illustrated in Figure l. l.
dH
" q C 0 2 " MMe e w O C H 3 O
NHS02Ph NHPhFl
Figure 1.1: Important Serine Aldebyde Equivalents.
NPhR O ~ R
O R = Boc, Cbz, Bn
dcHo
Rapoport first described the conversion of L-serine to D-amino acids in 1984
using a-suIfonamido acids 1.50 treated with excess organo-Li reagents or Grignard
reagents? These could be reduced directly to p-hydroxy-a-amino acids, erythro
configuration with NaB& (7:3 ratio), threo with L-selectride (99: 1) in good yield or to
the alkyl derivative via thioketal desulfurization or trïethylsilane reduction. Platinum
catdyzed oxidation and subsequent deprotection gave the desired D-amino acids in very
good overall yields (Scheme 1.23). However, the conditions used for reduction and
oxidation limit the functional groups that can be incorporated. A large scale synthesis
has aiso been developed for the preparation of a-amino ketones 1.54.62 This synthon has
been applied to the synthesis of various carbacephems6' and calicogorgin A."