Both trans and cis isomers
of 4-amino-3-halogenobut-2-enoic acid have been prepared as potential irreversible
inhibitors of the enzyme GABA- transaminase. trans-Addition of HX to
4-chlorobut-2-ynoic acid and subsequent amination gave the trans isomers (2; X
= Cl, Br, I), while the key step in the synthesis of
the cis isomers (3; X = Cl, Br) was the isomerization
to cis-4-bromo-3-halogenobut-2-enoic acids during allylic bromination. The
stereochemical assignments are supported by 1H and 13C
n.m.r. spectral data. A convenient preparation of cis-4- aminobut-2-enoic acid
by reduction of the bromo derivative is described, as well as the synthesis of
4-phthalimidobut-2-ynoic acid which is suitable for preparing radiolabelled
GABA of high specific activity.