Unexpected Synthesis of Conformationally Restricted Analogues of 7-Amino Butyric Acid(GABA):Mechanism Elucidation by Electrospray Ionization Mass Spectrometry

摘要

From previous results with lower homologues,dehydroiodination of the three alkenyl-beta-enamino esters 3a-c was expected to provide six-membered N-heterocyclic products.The reactions of 3a-c with triethylamine are found to lead,however,to the unexpected stereoselective synthesis of the trisubstituted cyclopentane derivatives 4a-c,as confirmed by IR and NMR spectroscopy.Cyclo-pentanes 4a-c bear two chiral centers and a y-amino ester moiety,and are therefore conformationally restricted analogues of y-amino butyric acid(GABA),which is the major inhibitory neurotransmitter in the central nervous system.Use of electrospray ionization mass(ESI-MS)and tandem mass spectromeiry(ESI-MS/MS)allowed the key iminium ion intermediates 5a-c~+,as well as the protonated molecules of both the reactant and final products,[3a-c + H]~+ and [4a-c + H]~+,to be intercepted and structurally characterized.From these findings a mechanism for this~-unexpected but synthetically attractive and efficient stereoselective reaction is proposed.