Sites of reaction of pilocarpine

Analysis of the sites of reaction of a biologically important compound, pil ocarpine, a molecule with imidazole and butyrolactone rings connected by a methylene bridge, has been accomplished in a quadrupole ion trap with the a im of characterizing its structure/reactivity relationships. Ion-molecule r eactions of pilocarpine with chemical ionizing agents, dimethyl ether (DME) , 2-methoxyethanol, and trimethyl berate (TMB), along with collision-activa ted dissociation elucidated the reaction sites of pilocarpine and made poss ible the comparison of structural features that affect sites of reaction. B ased on MS/MS experiments, methylation occurs on the imidazole ring upon re actions with CH3OCH2+ or (CH3OCH2CH2OH)H+ ions but methylation occurs on th e lactone ring for reactions with (CH3O)(2)B+ ions. Bracketing experiments with two model compounds, alpha-methyl-gamma-butyrolactoane and N-methyl im idazole, show the imidazole ring to have a greater gas-phase basicity and m ethyl cation affinity than the lactone ring. The contrast of methylation by TMB ions on the lactone ring is explained by initial addition of the dimet hoxyborinium ion, (CH3)(2)B+, on the imidazole ring with subsequent collisi onal activation promoting an intramolecular transfer of a methyl group to t he lactone ring with concurrent loss of CH3OBO. Semiempirical molecular orb ital calculations are undertaken to further address the favored reaction si tes. (C) 1999 American Society for Mass Spectrometry.