Synthesis of some substituted 4-Aminobut-2-enoic acids as analogues of the neurotransmitter GABA

Allylic bromination of a series of α,β-unsaturated acids with N- bromosuccinimide gave crude products which could be aminated conveniently in liquid ammonia to prepare the substituted 4-aminobut-2- enoic acid (4-aminocrotonic acid) derivatives (4a-f) in low to moderate yields. The assignment of the trans configuration of the carboxyl and aminomethyl groups about the double bond of the amino acid products is supported by chemical studies and proton magnetic resonance spectral data. The procedure worked conveniently with methylamine to give the unsaturated secondary amino acids (8a,b). Methylamine was also shown to remove a phthalimido protecting group cleanly in the presence of an α,β-unsaturated acid functionality.