Low Energy Collision-Induced Dissociation of Azepine Pictet–Spengler Adducts of N_ω-Methylserotonin

Cimitrypazepines are a class of natural products produced by Pictet-Spengler condensation of Nω-methylserotonin and aldehydes in a manner that produces a seven-membered azepine ring. In this study, the fragmentation behavior of this class of molecules under low-energy CID was investigated in detail. Proposed mechanisms of fragmentation were supported by deuterium labeling and DFT calculations. Loss of methylamine and methylenimine were dominant fragmentation pathways of analogs containing an aliphatic side chain. Loss of methylenimine was found to proceed via unusual methyl cation transfer. Fragmentation of analogs containing an aromatic side chain was strongly influenced by the nature of the substituents and proceeded via a novel retro-Pictet-Spengler pathway and involvement of ion-neutral complexes. In some cases, a gas-phase interconversion between the azepine and β-carboline ring was observed during fragmentation. Detailed analysis of fragmentation behavior provided in this study will serve as a valuable guide for the discovery of new analogs from natural sources.