title: Unexpected synthesis of conformationally restricted analogues of gamma-amino butyric acid (GABA): mechanism elucidation by electrospray ionization mass spectrometry.
abstract: 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. Cyclopentanes 4a-c bear two chiral centers and a gamma-amino ester moiety, and are therefore conformationally restricted analogues of gamma-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 spectrometry (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.
authors.affiliation: Institute of Chemistry, University of São Paulo-USP, São Paulo SP, 05508-900, Brazil. hmferraz@iq.usp.br
authors.forename: Helena M C
authors.initials: HM
authors.lastname: Ferraz
authors.forename: Fernando L C
authors.initials: FL
authors.lastname: Pereira
authors.forename: Erika R S
authors.initials: ER
authors.lastname: Gonçalo
authors.forename: Leonardo S
authors.initials: LS
authors.lastname: Santos
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
mesh_terms: D020650:Combinatorial Chemistry Techniques; D003517:Cyclopentanes / Q000138:chemical synthesis*; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D003517:Cyclopentanes; D005680:gamma-Aminobutyric Acid