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

of Rheum rhaponticum over forty years agoa and since that time has been shown to be a
constituent of a large variety of flowenng plants, fems, mosses and mushrooms?
4.7 R'=&H. R~~I-I
4.9 R'=R- OH, R2= H
4.10 R'&o~~, R2=R3= H
Scheme 4.1
The best-known y-substituted-a-amino acid is ycarboxyglutamic acid 4.10 which
is a component of several vitamin K dependent hemostasis proteins, including
prothrombin. 'O The y-dicartmxylate moiety binds ca2+ ions to induce a conformational
change in numerous hemostasis proteins providing a biofeedback route for the control of
bleeding. First detected in 1974 this calcium binding amino acid has also been
discovered in the conantokins, potent N-methylaspartate receptor agonist peptides
isolated from the venom of the cone snail Conus geographus.."
y-Aminoglutamic acid 4.11 and y-haloglutarnic acids 4.12 have not been
identified in nature to date but the compounds are of interest therapeuticaily as will be
discussed (vide infia).