Z. V. I. Zaretskii

Translational energy release and stereochemistry of steroids

Abstract The measurement of the translational energy, T, released during a unimolecular ionic decomposition in the mass spectrometer in epimeric steroid hydrocarbons of the androstane, pregnane and cholestane series differing in the mode of the rings A/B and C/D junctions, as well as in their deuterated analogues has been employed for the first time with a view to providing a simple and rapid method for identifying the configuration of epimeric centres. A major common reaction, the loss of CH3· from the molecular ion has been chosen for the measurements. It is found that in most cases the 14β- and β-isomers release smaller amounts of translational energy for CH3· loss than their 14α- and 5α-counterparts.

The determination of ring junction stereochemistry in steroids using mass-analysed ion kinetic energy spectrometry

Abstract The unimolecular mass-analysed ion kinetic energy (MIKE) spectra of 9 pairs of hydrocarbon and ketone steroid isomers, differing only in the stereochemistry at the A/B and C/D ring junctions, have been measured and are discussed with a view to unambiguous structural identification. Reproducible differences in the MIKE spectra are observed, which are large enough in certain instances to suggest that MIKE spectrometry may be used for determining the stereochemistry of the A/B and C/D ring junctions in steroidal isomers, even if the second isomer is not available. This fortunate situation is rarely observed in conventional mass spectrometry of stereoisomeric steroids. Furthermore, these differences in the MIKE spectra may be correlated with differences in strain energy between configurational isomers. The sensitivity of MIKE spectrometry to differences in strain energies makes it a potentially powerful stereochemical probe.

Appearance-ionization potentials differences as a guide to the relative stabilities of the cis- and trans-A/B-steroids

Abstract The ionization potentials of cis- and trans-A/B-steroids of the androstane and pregnane series, as well as the appearance potentials of the M+-Me ions have been determined. The approximate activation energies (obtained as the AP-IP differences) for the loss of an angular Me from the molecular ion were found to be higher in the case of the more stable trans-A/B (5α)-steroids as compared to their cis (5β)-isomers.

Withaphysalin C, a naturally occurring 13,14-seco-steroid

The structure of withaphysalin C, a new naturally occurring steroidal lactone of the withanolide group, isolated from Physalis minima(Solanaceae), has been elucidated. This is a 13,14-seco-steroid closely related to withaphysalin A. The lack of a 17α-OH precluded the formation of a 17 → 14 hemiacetal as in the physalins, leading to the alternative formation of a 13 → 14 hemiacetal.

Mass spectrometry of metastable ions and stereochemistry of steroids

Abstract The elimination of water from metastable molecular ions of epimeric hydroxy steroids of the cholestane and androstane series containing a hydroxyl group in the conformationally flexible ring A has been studied. The measurement of translational energy released during the loss of water, and collision-induced decomposition mass-analysed ion kinetic energy spectrometry were the techniques used. It was found that it is possible to distinguish the different configurations of the hydroxy steroids of these series on the basis of the CID MIKE spectra of (MH2O)+ ions formed by dehydration of metastable molecular ions in the first field-free region of a reversed geometry double-focusing mass spectrometer.

9(11)-Secoestra-11,17-dioic acids and related compounds

Abstract While hydrogenations of 2b furnished a mixture in which the rac 14α isomer 8b predominated, the rac lactone 6 was hydrogenolyzed to give the rac 14β diacid 9a. Clemmensen reduction of 6 gave the rac 14α tetrahydro compound 7a. Another route to 8 involved conversion of the d-ketoacid 11b into 23b via the cyanolactone 20b or the amidolactone 21b. Base-catalyzed elimination at 206° yielded the Δ16 diester 27 which was hydrogenated to 8c. An analogous conversion was also carried out in the ring B reduced series 13 → 20a + 21a → 23a → 25a → 26. In the 14β series, using the same sequence of reactions, the rac ketoacid 10a was transformed into the rac lactone ester 29. In distinction from the 14α series, treatment with alkali at 206° gave only partial elimination, the double bond migrating to the 14,15 position to furnish 2. Evidence is presented that amides of the ketoacid 13a exist in the hydroxylactam form 30 and can be readily O-alkylated to furnish 22. Attempts to aromatize ring B of 13a with DDQ led to lactones 15 and 16, while reaction of the ester 13b with DDQ gave the pentaene 17 and the hexaene 18, establishing that dehydrogenation proceeded stepwise in the sequence Δ8, Δ14 and finally Δ6.

Determination of the configuration of epimeric diols of vitamin D3 series by mass spectrometry

The mass spectral elimination of water in epimeric 1,3-diols of vitamin D3 (colecalciferol) series has been investigated. It was found that the mass spectra of these steroisomers differ sharply in the relative intensities of the ions M-H2O (m/e 382) and a-H2O (m/e +/- 34), where ion a (formed via formal cleavage of the 7, 8-double bond) is characteristic of vitamin D3 and its derivatives. So while epimeric 1, 3-diols of vitamin D3 series have very close UV and NMR characteristics, the comparison of the ratios of the peaks M-H2O and M.+, a-H2O and a, respectively, makes it possible to distinguish between stereoisomeric 1 alpha, 3 beta-, 1 beta, 3 beta-, 1 alpha, 3 alpha- and 1 beta, 3 alpha-diols using their mass spectra.