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

pyridoxal phosphate dependent enzyme catdyzing a step in methionine biosynthesist it
can also catdyze B- and y-replacement, p- and y-elimination and a- and p-hydrogen
exchange in a number of arnino a~ids.~ The simplest a,B-unsahuateci a-amino acid, 2-
amino-3-butenoic acid, also known as vinylglycine 3.7, was not isolated until 1974 when
the Denantiorner was found in the mushn>om Rhodophylllus nidor~sus.'~
Most of the interest in a$-unsaturated a-amino acids is due to their ability to act
as suicide substrates or mechanistic probes of pyridoxal phosphate (PLP) dependent
enzymes. These enzymes are involved in cataiyzing chernical changes at the a-. P- or y-
carbons of comrnon amino acids and are a vital link in many biosynthetic pathways. The
concept of suicide substrates in general has been extensively reviewed" as has the
specific use of vinylglycines with respect to PLP dependent enzymes."
Suicide substrates, or enzyme activated inhibitors, are chernically unreactive
substances which possess latent reactive groups that are specifically unmasked through
the action of the target enzyme. Once generated, the reactive intermediate irreversibly
inactivates the enzyme by covalently reacting with an active site residue. Since the
suicide substrate must be pre-activated by the enzyme, these substrates can be designed to
target specific classes of enzymes. The mechanism for inactivation of PLP enzymes is