3α,5α-四氢醛固酮的合成
Synthesis of 3 alpha, 5 alpha-tetrahydroaldosterone.
作者信息
Harnik M, Kashman Y, Morris D J
出版信息
J Steroid Biochem. 1984 Jun;20(6A):1313-20. doi: 10.1016/0022-4731(84)90162-6.
3 alpha, 5 alpha-Tetrahydroaldosterone (12a), a metabolite of aldosterone, has been synthesized from the lactone 2a or, preferably 11 beta, 21-dihydroxy-5-pregnene-3,20-dione-18-oic acid 3,20-di-(ethylene glycol)-ketal (18----11) lactone 21-acetate (6b), via 11 beta, 21-dihydroxy-5 alpha-pregnane-3,20-dione-18-oic acid 3,20-di-(ethylene glycol) ketal (18----11) lactone 21-acetate (4b). Selective hydrolysis of the latter at C-3 furnished the monoketal 5 which, on reduction with potassium tri-sec-butylborohydride, yielded predominantly 3 alpha, 11 beta, 21-trihydroxy-5 alpha-pregnan-20-one-18-oic acid 20-(ethylene glycol)-ketal (18----11) lactone (8a) and its acetate 8b. Further reduction with diisobutylaluminum hydride afforded 3 alpha, 5 alpha-tetrahydroaldosterone-20-ketal (10a), which was directly hydrolyzed to 12a with dilute acid in tetrahydrofuran-dioxan. Periodate oxidation led to the gamma-etiolactone 14a, which was then further converted into 5 alpha-dihydroaldosterone-gamma-etiolactone (14c).
3α,5α-四氢醛固酮（12a），醛固酮的一种代谢产物，已由内酯2a或更优选地由11β,21-二羟基-5-孕烯-3,20-二酮-18-酸3,20-二（乙二醇）-缩酮（18→11）内酯21-乙酸酯（6b），通过11β,21-二羟基-5α-孕烷-3,20-二酮-18-酸3,20-二（乙二醇）缩酮（18→11）内酯21-乙酸酯（4b）合成。后者在C-3位的选择性水解得到单缩酮5，用三叔丁基硼氢化钾还原后，主要生成3α,11β,21-三羟基-5α-孕烷-20-酮-18-酸20-（乙二醇）-缩酮（18→11）内酯（8a）及其乙酸酯8b。用二异丁基氢化铝进一步还原得到3α,5α-四氢醛固酮-20-缩酮（10a），其在四氢呋喃-二氧六环中用稀酸直接水解为12a。高碘酸盐氧化生成γ-乙内酰脲内酯14a，然后进一步转化为5α-二氢醛固酮-γ-乙内酰脲内酯（14c）。
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