Elucidation of electron ionization mass spectrometric fragmentation pathways of trimethylsilyl ether derivatives of vicinal diols deriving from haplamine by collision‐induced dissociation gas chromatography/tandem mass spectrometry and 18O labelling

Abstract

Formation of vicinal diols was observed after in vitro and in vivo studies of the natural product haplamine (9-methoxy-2,2-dimethyl-2,6-dihydropyrano[3,2-c]quinolin-5-one). These compounds, identified as trans- and cis-3,4-dihydroxy-9-methoxy-2,2-dimethyl-2,3,4,6-tetrahydropyrano[3,2-c]quinolin-5-ones and trans- and cis-3,4,9-trihydroxy-2,2-dimethyl-2,3,4,6-tetrahydropyrano[3,2-c]quinolin-5-ones, have a potential interest in oncology. It is therefore essential to elucidate their electron ionization mass spectrometric (EIMS) fragmentation pathways. EIMS fragmentation pathways of trimethylsilyl (TMS) derivatives of 3,4-dihydroxy- and 3,4,9-trihydroxyhaplamines were investigated. These pathways have been substantiated by: (i) comparison with EI mass spectra of structural homologues (silylated diols obtained from various chromenes and 1,2-dihydronaphthalene), (ii) low-energy collision-induced dissociation (CID) gas chromatography/tandem mass spectrometry (GC/MS/MS) and (iii) (18)O labelling. CID-MS/MS analyses and (18)O labelling demonstrated that EI mass spectral fragmentation of these TMS derivatives involves a transannular cleavage of the pyran ring with formation of a characteristic intense cyclic ion. The study of the mass spectra of TMS derivatives of different chromenes and 1,2-dihydroxynaphthalene allowed to confirm the proposed fragmentation pathways and to show that they act only when the pyran ring is present. Elimination of the neutral element [(CH3)2=C(H)OSi(CH3)3] and formation of cyclic ions play a key role during EI mass spectral fragmentation of the TMS derivatives of 3,4-dihydroxy- and 3,4,9-trihydroxyhaplamines. These fragmentation pathways could be generalized to TMS derivatives of cyclic compounds possessing vicinal diols close to a pyran ring.