Structural studies on bioactive-compounds. Part 7. The design and synthesis of α-substituted serines as prospective inhibitors of serine hydroxymethyltransferase

Abstract

A short series of α-substituted analogues of serine, designed as enzyme-activated, irreversible inhibitors of serine hydroxymethyltransferase, has been prepared. (±)-α-Allyl- and (±)-α-prop-2-ynyl-serine were synthesised by appropriate alkylation of the anion derived from ethyl acetamidocyanoacetate, followed by selective reduction of the ester function and hydrolysis of protecting groups. Acetoxymethylation of the anion derived from methyl 2-(benzylideneamino)but-2-enoate gave (±)-α-vinylserine after deprotection. These novel analogues of serine were largely inactive as inhibitors of the enzyme, except that (±)-α-vinylserine showed weak competitive inhibition.