Stereospecific Alkylation of the Schiff Base Ester of Alanine with 2-Substituted-(E)- and -(Z)-vinyl Bromides. An Efficient Synthesis of 2-Methyl-(E)-3,4-didehydroglutamic Acid, a Potent Substrate-Induced Irreversible Inhibitor of L-Glutamate-1-decarboxylase.

Article abstract of DOI:10.1021/jo01304a021

The nucleophilic vinylic substitution by the enolate of methyl N-benzylidenealanate (1) of (E)- and (Z)-vinylbromides 4 and 5 has been examined as an approach to the synthesis of the E and Z isomers of 2-methyl-3,4-didehydroglutamic acid.Under aprotic conditions, the nucleophilic displacement has been found to proceed stereospecifically with retention of configuration of the double bond to afford in good yield the corresponding (E)- and (Z)-substituted products.The configuration of the substitution products has been assigned from the analysis of their 1H NMR spectra on the basis of the value of the coupling constant of the vicinal vinyl ic protons.Subsequent removal of the protecting groups from the substitution products 6 in the E series gives the corresponding 2-methyl-(E)-3,4-didehydroglutamic acid derivatives 2 in good yield.The Z isomers 3 prove to be very unstable and have not been isolated.