Synthesis and identification of twelve A-ring reduced 6α- and 6β-hydroxylated compounds derived from 11-deoxycortisol, corticosterone and 11-dehydrocorticosterone
| Autor: | J.C. van der Molen, R.W.J. Zijlstra, G.T. Nagel, J. Hartstra, N.M. Drayer, W.H. Kruizinga, G.P.B. Kraan, B.G. Wolthers |
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| Rok vydání: | 1994 |
| Předmět: |
3-Hydroxysteroid Dehydrogenases
Magnetic Resonance Spectroscopy Double bond Stereochemistry Endocrinology Diabetes and Metabolism medicine.medical_treatment Cortodoxone Clinical Biochemistry Hydroxylation Biochemistry Chemical synthesis High-performance liquid chromatography Gas Chromatography-Mass Spectrometry Steroid Endocrinology medicine Molecular Biology Chromatography High Pressure Liquid chemistry.chemical_classification Chromatography Chemistry Elution Cell Biology 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) NAD Mass spectrum Molecular Medicine Steroids Epimer Gas chromatography–mass spectrometry Corticosterone Oxidation-Reduction |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 49:233-244 |
| ISSN: | 0960-0760 |
| Popis: | The synthesis and identification of 12 A-ring reduced 6 alpha-(and 6 beta-)hydroxylated compounds derived from 11-deoxycortisol (S), corticosterone (B) and 11-dehydrocorticosterone (A) are reported here. These steroids were prepared in two steps from the corresponding 6 6 alpha-(and 6 beta-)hydroxy-4-pregnene-3-ones. Selective reduction of the 4,5 double bond yielded 12 6 alpha-(and 6 beta)hydroxy-5 alpha-(and 5 beta)pregnane-3,20-diones. Enzymatic reduction of these compounds with NADH and 3 alpha-hydroxysteroid dehydrogenase yielded the corresponding tetrahydro steroids. The steroids were characterized by high performance liquid chromatography (HPLC), gas chromatography mass spectrometry (GC and GC/MS) and in part by 1H-NMR. 6 beta OH-THS and 6 beta OH-5 alpha THS were identified by 1H-NMR. The structures of the two precursors, i.e. 6 beta OH-5 beta DHS and 6 beta OH-5 alpha DHS were confirmed by 1H-NMR using two-dimensional spectra. 6 alpha OH-THS was identified by comparing its HPLC, GC and MS data with those of the steroid obtained by enzymatic oxidation of the standard reference steroid 6 alpha OH-20 beta HHS to the corresponding 20-ketosteroid. The other steroids, e.g. 6 alpha OH-THB and 6 alpha OH-5 alpha THB were identified by using the proved sequence of elution of each of the epimer pairs on the normal phase HPLC column (5 alpha5 beta), and by the reversed order of elution of the same epimer pair as the methoxime-trimethylsilyl ethers on the GC column (5 alpha5 beta) and by the mass spectra, with the exception of 6 beta OH-THA. |
| Databáze: | OpenAIRE |
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