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

acids will be presented including a number of selected routes that have proven to be of
greatest importance and general utility in leading to enantiomerically pure amino acids.
Methods that are specific to classes of amino acids will be discussed in the relevant
chapter- For a more detailed review of methods for the stereoselective synthesis of a-
amino acids, readers are referred to the excellent reviews by Williarn~'~ and Duthaler."
1.2 Chernical Synthesis of Racemic a-Amino Acids
Prior to the 1970's, the most widely used procedures for the synthesis of a-amino
acids led to racemic compounds. Many of these routes were based on classical syntheses
and could be categorïzed into three groups: addition of the arnino or carboxy function to
the side Chain, alkylation of glycine derivatives and other methods.
1.2.1 Addition of the Amino or Carboxy Function to the Side Chain.
Racemic a-amino acids can be synthesized by the a-amination of a synthon
containing a carboxyl group or conversely, by the a-carboxylation of an amine
containing synthon. The first reported synthesis of an a-amino acid, in 1850 by the
S trecker s ynthesis is an example of this method (Scheme 1.1). ''
Scheme 1.1
R
R
R
NH or
HCN
acid or
RCHo ~2 AOH KCN Y&CN .k.iW ~2 IiTI\C02H
The Strecker synthesis is widely used in industry where the racemic arnino acid is
N-acylated and subsequently enzymatically resolved to give the desired optically pure