Cerný I, Fajkos J, Pouzar V
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague.
Steroids. 1996 Feb;61(2):58-64. doi: 10.1016/0039-128x(95)00196-w.
Reaction of 3 beta-hydroxyandrosta-5,15-dien-17-one with 4-methoxybenzyl alcohol followed by acetylation gave mainly 15 beta-[(4-methoxyphenyl)methoxy]-17-oxoandrost-5-en-3 beta-yl acetate. This product was transformed by borohydride reduction and organosilyl derivatization into the orthogonally protected 17 beta-(dimethylthexylsiloxy)-15 beta-[(4-methoxyphenyl)methoxy]androst-5-en-3 beta-yl acetate and 17 beta-(dimethylisopropylsiloxy)-15 beta-[4-methoxyphenyl)methoxy]androst-5-en-3 beta-yl acetate. After deacetylation, these intermediates were submitted to Oppenauer oxidation and both yielded testosterone derivatives 17 beta-(dimethylthexylsiloxy)-15 beta-[(4-methoxyphenyl)methoxy]androst-4- en-3-one and 17 beta-(dimethylisopropylsiloxy)-15 beta-[(4-methoxyphenyl)- methoxy]androst-4-en-3-one. Removal of the (4-methoxyphenyl)methyl group from position 15 by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone treatment gave the partially protected derivatives 17 beta-(dimethylthexylsiloxy)-15 beta-hydroxyandrost-4-en-3-one and 17 beta-(dimethylisopropylsiloxy)-15 beta-hydroxyandrost-4-en-3-one. After acidic deprotection, the dimethylthexylsilyl derivative yielded 15 beta-hydroxytestosterone (15 beta,17 beta-dihydroxyandrost-4-en-3-one). Dimethylisopropylsilyl derivative was converted to the corresponding 15-hemisuccinate and 15-hemiglutarate (17 beta-hydroxy-3-oxoandrost-4-en-15 beta-yl 15-hemisuccinate and 15-hemiglutarate, respectively), which were designed as model haptens for immunoassay studies.
3β-羟基雄甾-5,15-二烯-17-酮与4-甲氧基苄醇反应，随后进行乙酰化，主要得到15β-[(4-甲氧基苯基)甲氧基]-17-氧代雄甾-5-烯-3β-基乙酸酯。该产物经硼氢化物还原和有机硅烷基衍生化，转化为正交保护的17β-(二甲基叔丁基硅氧基)-15β-[(4-甲氧基苯基)甲氧基]雄甾-5-烯-3β-基乙酸酯和17β-(二甲基异丙基硅氧基)-15β-[(4-甲氧基苯基)甲氧基]雄甾-5-烯-3β-基乙酸酯。脱乙酰化后，将这些中间体进行欧芬脑尔氧化，二者均得到睾酮衍生物17β-(二甲基叔丁基硅氧基)-15β-[(4-甲氧基苯基)甲氧基]雄甾-4-烯-3-酮和17β-(二甲基异丙基硅氧基)-15β-[(4-甲氧基苯基)甲氧基]雄甾-4-烯-3-酮。用2,3-二氯-5,6-二氰基-1,4-苯醌处理去除15位的(4-甲氧基苯基)甲基，得到部分保护的衍生物17β-(二甲基叔丁基硅氧基)-15β-羟基雄甾-4-烯-3-酮和17β-(二甲基异丙基硅氧基)-15β-羟基雄甾-4-烯-3-酮。酸性脱保护后，二甲基叔丁基硅烷基衍生物得到15β-羟基睾酮(15β,17β-二羟基雄甾-4-烯-3-酮)。二甲基异丙基硅烷基衍生物转化为相应的15-半琥珀酸酯和15-半戊二酸酯(分别为17β-羟基-3-氧代雄甾-4-烯-15β-基15-半琥珀酸酯和15-半戊二酸酯)，它们被设计用作免疫分析研究的模型半抗原。
