Schänzer W, Opfermann G, Donike M
Institut für Biochemie, Deutsche Sporthochschule, Cologne, Germany.
Steroids. 1992 Nov;57(11):537-50. doi: 10.1016/0039-128x(92)90023-3.
The 17-epimers of the anabolic steroids bolasterone (I), 4-chlorodehydromethyltestosterone (II), fluoxymesterone (III), furazabol (IV), metandienone (V), mestanolone (VI), methyltestosterone (VII), methandriol (VIII), oxandrolone (IX), oxymesterone (X), oxymetholone (XI), stanozolol (XII), and the human metabolites 7 alpha,17 alpha-dimethyl-5 beta-androstane-3 alpha,17 beta-diol (XIII) (metabolite of I), 6 beta-hydroxymetandienone (XIV) (metabolite of V), 17 alpha-methyl-5 beta-androst-1-ene-3 alpha,17 beta-diol (XV) (metabolite of V), 3'-hydroxystanozolol (XVI) (metabolite of XII), as well as the reference substances 17 beta-hydroxy-17 alpha-methyl-5 beta-androstan-3-one (XVII), 17 beta-hydroxy-17 alpha-methyl-5 beta-androst-1-en-3-one (XVIII) (also a metabolite of V), the four isomers 17 alpha-methyl-5 alpha-androstane-3 alpha,17 beta-diol (XIX) (also a metabolite of VI, VII, and XI), 17 alpha-methyl-5 alpha-androstane-3 beta,17 beta-diol (XX), 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol (XXI) (also a metabolite of V, VII, and VIII), 17 alpha-methyl-5 beta-androstane-3 beta,17 beta-diol (XXII), and 17 beta-hydroxy-7 alpha,17 alpha-dimethyl-5 beta-androstan-3-one (XXIII) were synthesized via a 17 beta-sulfate that spontaneously hydrolyzed in water to several dehydration products, and to the 17 alpha-hydroxy-17 beta-methyl epimer. The 17 beta-sulfate was prepared by reaction of the 17 beta-hydroxy-17 alpha-methyl steroid with sulfur trioxide pyridine complex. The 17 beta-methyl epimers are eluted in gas chromatography as trimethylsilyl derivatives from a capillary SE-54 or OV-1 column 70-170 methylen units before the corresponding 17 alpha-methyl epimer. The electron impact mass spectra of the underivatized and trimethylsilylated epimers are in most cases identical and only for I, II, and V was a differentiation between the 17-epimers possible. 1H nuclear magnetic resonance (NMR) spectra show for the 17 beta-methyl epimer a chemical shift for the C-18 protons (singlet) of about 0.175 ppm (in deuterochloroform) to a lower field. 13C NMR spectra display differences for the 17-epimeric steroids in shielding effects for carbons 12-18 and 20. Excretion studies with I-XII with identification and quantification of 17-epimeric metabolites indicate that the extent of 17-epimerization depends on the A-ring structure and shows a great variation for the different 17 alpha-methyl anabolic steroids.
合成代谢类固醇勃拉睾酮（I）、4-氯去氢甲基睾酮（II）、氟甲睾酮（III）、呋咱甲氢龙（IV）、美雄酮（V）、美睾酮（VI）、甲睾酮（VII）、美雄醇（VIII）、氧雄龙（IX）、羟甲睾酮（X）、羟甲烯龙（XI）、司坦唑醇（XII）的17-差向异构体，以及人体代谢物7α,17α-二甲基-5β-雄甾烷-3α,17β-二醇（XIII）（I的代谢物）、6β-羟基美雄酮（XIV）（V的代谢物）、17α-甲基-5β-雄甾-1-烯-3α,17β-二醇（XV）（V的代谢物）、3'-羟基司坦唑醇（XVI）（XII的代谢物），以及参考物质17β-羟基-17α-甲基-5β-雄甾烷-3-酮（XVII）、17β-羟基-17α-甲基-5β-雄甾-1-烯-3-酮（XVIII）（也是V的代谢物）、四种异构体17α-甲基-5α-雄甾烷-3α,17β-二醇（XIX）（也是VI、VII和XI的代谢物）、17α-甲基-5α-雄甾烷-3β,17β-二醇（XX）、17α-甲基-5β-雄甾烷-3α,17β-二醇（XXI）（也是V、VII和VIII的代谢物）、17α-甲基-5β-雄甾烷-3β,17β-二醇（XXII）和17β-羟基-7α,17α-二甲基-5β-雄甾烷-3-酮（XXIII）是通过17β-硫酸盐合成的，该硫酸盐在水中自发水解为几种脱水产物以及17α-羟基-17β-甲基差向异构体。17β-硫酸盐是通过17β-羟基-17α-甲基类固醇与三氧化硫吡啶络合物反应制备的。在气相色谱中，17β-甲基差向异构体作为三甲基硅烷基衍生物从毛细管SE-54或OV-1柱上洗脱，比相应的17α-甲基差向异构体早70 - 170个亚甲基单元。未衍生化和三甲基硅烷基化差向异构体的电子轰击质谱在大多数情况下是相同的，只有对于I、II和V，才有可能区分17-差向异构体。1H核磁共振（NMR）光谱显示，对于17β-甲基差向异构体，C-18质子（单峰）的化学位移在氘代氯仿中约为0.175 ppm，向低场移动。13C NMR光谱显示17-差向异构类固醇在碳12 - 18和20的屏蔽效应方面存在差异。对I - XII进行的排泄研究以及对17-差向异构代谢物的鉴定和定量表明，17-差向异构化的程度取决于A环结构，并且在不同的17α-甲基合成代谢类固醇中差异很大。
