Mass Spectrometry in Structural and Stereochemical Problems. LXV.¹ Synthesis and Fragmentation Behavior of 15-Keto Steroids. The Importance of Interatomic Distance in the McLafferty Rearrangement²

A highly efficient, stereoselective oxyfunctionalization of unactivated carbons in steroids with dimethyldioxirane†

“…For instance, identification of 16-oxo steroids 16, 21, 22, 24, and 25 was made as follows: in the 1 H-NMR spectrum, the 18-methyl proton signal is shifted downfield by ca. 0.15-0.16 ppm, compared with that of the respective parent compounds 3-5, 7b while the C-20 carbon signal in the 13 C-NMR spectrum is shifted to up field by 4.5-4.9 ppm due to the γ-effect of the ketogenesis, and the resonance position of the C-16 carbon is in good agreement with that (δ C 217.4 ppm) of methyl 3,7,16-trioxo-5β-cholan-24-oate [unpublished]; diagnostic fragment ions occurring in the MS of the 16-oxo steroids, 24 which are usually absent in those of 15-oxo analogs, 25 supported the structures proposed. Furthermore, the presence of the cyclic γ-lactone ring at the C-17 position in compound 18 was elucidated by a characteristic absorption peak at 1771 cm Ϫ1 in the IR spectrum, a considerable down field shift of the C-21 methyl protons (relative to that of 3) at δ 1.45 as a singlet, 26 and the disappearance of the methyl ester protons in the 1 H-NMR spectrum as well as those of the C-20 (δ C 88.4) and C-24 (δ C 177.4) signals and the absence of a C-25 methyl ester signal (δ C ≈ 51.5) in the 13 C-NMR spectrum, and intense fragment ions at m/z 414 (14%) and 354 (85%) forming by the loss of one and two acetic acid molecules from the molecular ion, respectively.…”

“…The observation indicates that a methyl ester at C-24 in 1 is also a deactivating group against DMDO reaction. In particular, for compound 5 possessing four deactivating groups (three acetoxy groups and one methyl ester), total conversion into the oxyfunctionalized products (23)(24)(25) was only 54%, even though the DMDO reaction was carried out over a period of 60 h.…”

Mass Spectrometry in Doping Control Analysis

“…Extensive studies regarding the metabolic pathways of AAS [19] as well as mass spectrometric behavior of target compounds after EI with or without derivatization have been conducted allowing the unambiguous identification of respective xenobiotic agents. Budzikiewicz, Djerassi, and co-workers did extensive research on dissociation routes of common natural steroids including various derivatives such as ketals and acetates, and a comprehensive summary was published in 1964 [20] followed by numerous additional articles [21][22][23][24][25]. The trace analysis in doping controls has required derivatization in order to improve chromatographic as well as mass spectrometric properties of target compounds, and because of the ease of trimethylsilylation (TMS) of steroids by Nmethyl-N-trimethylsilyltrifluoroacetamide (MSTFA) [26,27] or its mixture with ammonium iodide and ethanethiol promoting the in-situ formation of the highly reactive trimethyliodosilane (TMIS) almost all commonly accepted assays are based on the detection of trimethylsilylated steroid derivatives [28][29][30][31].…”

A review of the total synthesis of the most important marine natural products in the Red Sea

“…Cholesterol was isolated from the Red Sea sponge Negombata corticata, 1 the total synthesis of which was reported by Marino and others. 15,16 They applied a stereospecific epoxidation of α, βunsaturated ketone 22 using meta-chloroperoxybenzoic acid, with attack of a peroxy acid at the Re side rather than the Se side of the molecule because of steric hindrance of the methyl group. This was followed by protection of the OH group in the equatorial position with tert-butyldimethylsilyl.…”