Laboratoire de Pharmacocinétique et Toxicocinétique (EA 3286), Faculté de Pharmacie, 13385, Marseille, France.
Rapid Commun Mass Spectrom. 2014 May 15;28(9):1004-10. doi: 10.1002/rcm.6879.
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.
在天然产物哈普林（9-甲氧基-2,2-二甲基-2,6-二氢哒嗪并[3,2-c]喹啉-5-酮）的体外和体内研究中观察到顺式和反式邻二醇的形成。这些化合物被鉴定为顺式和反式 3,4-二羟基-9-甲氧基-2,2-二甲基-2,3,4,6-四氢哒嗪并[3,2-c]喹啉-5-酮和顺式和反式 3,4,9-三羟基-2,2-二甲基-2,3,4,6-四氢哒嗪并[3,2-c]喹啉-5-酮，它们在肿瘤学中有潜在的应用价值。因此，阐明它们的电子电离质谱（EIMS）裂解途径至关重要。
研究了 3,4-二羟基和 3,4,9-三羟基哈普林的三甲基硅基（TMS）衍生物的 EIMS 裂解途径。这些途径通过以下方法得到证实：（i）与结构类似物（各种色烯和 1,2-二氢萘获得的硅烷化二醇）的 EI 质谱进行比较，（ii）低能碰撞诱导解离（CID）气相色谱/串联质谱（GC/MS/MS）和（iii）（18）O 标记。
CID-MS/MS 分析和（18）O 标记表明，这些 TMS 衍生物的 EI 质谱裂解涉及吡喃环的transannular 裂解，形成特征强烈的环状离子。对不同色烯和 1,2-二羟基萘的 TMS 衍生物的质谱研究证实了所提出的裂解途径，并表明只有当吡喃环存在时才会发生这些途径。
在 3,4-二羟基和 3,4,9-三羟基哈普林的 TMS 衍生物的 EI 质谱裂解中，中性元素[(CH3)2=C(H)OSi(CH3)3]的消除和环状离子的形成起着关键作用。这些裂解途径可以推广到具有靠近吡喃环的邻二醇的环状化合物的 TMS 衍生物。
