18,19-二羟基皮质酮的合成

Synthesis of 18,19-dihydroxycorticosterone.

作者信息

Harnik M, Carmely S, Cojocaru M, Kashman Y

出版信息

Steroids. 1986 Feb-Mar;47(2-3):205-13. doi: 10.1016/0039-128x(86)90089-9.

Abstract

A four-step synthesis of 18,19-dihydroxycorticosterone 5c, starting with 19,21-dihydroxy-3,20-dioxopregn-5-ene-18,11 beta-lactone-di-(ethylene ketal) 2, is presented. Reduction of 2 with sodium aluminum bis-(methoxyethoxy)hydride gave 11 beta,18,19,21-tetrahydroxy-pregn-5-ene-3,20-dione-di-(ethylene ketal) 3a. Acetylation furnished the corresponding 18,19,21-triacetate 3b, which on treatment with a mixture of perchloric and acetic acids gave 18,19-dihydroxycorticosterone 18,19,21-triacetate 4b. Mild saponification yielded the title compound which, on the basis of ir and nmr spectra, exists as one C-20 isomer of the hemiacetal structure 5c. Periodate oxidation of 5c gave the expected 11 beta, 19-dihydroxy-3-oxoandrost-4-ene-17 beta, 18-carbolactone 6b.

摘要

本文介绍了以19,21 - 二羟基 - 3,20 - 二氧代孕甾 - 5 - 烯 - 18,11β - 内酯 - 二（亚乙基缩酮）2为起始原料，四步合成18,19 - 二羟基皮质酮5c的方法。用双（甲氧基乙氧基）氢化铝钠还原2得到11β,18,19,21 - 四羟基 - 孕甾 - 5 - 烯 - 3,20 - 二酮 - 二（亚乙基缩酮）3a。乙酰化反应得到相应的18,19,21 - 三乙酸酯3b，用高氯酸和乙酸的混合物处理3b得到18,19 - 二羟基皮质酮18,19,21 - 三乙酸酯4b。温和皂化反应得到标题化合物，根据红外光谱和核磁共振光谱，该化合物以半缩醛结构5c的一种C - 20异构体形式存在。5c经高碘酸盐氧化得到预期的11β,19 - 二羟基 - 3 - 氧代雄甾 - 4 - 烯 - 17β,18 - 内酯6b。