Synthesis of the 1β-Hydroxylated Bile Acids, Unusual Bile Acids in Human Biological Fluids.
Synthesis of the 1β-Hydroxylated Bile Acids, Unusual Bile Acids in Human Biological Fluids.
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1β-羟基胆汁酸的合成，人体生物液中不寻常的胆汁酸。
DOI：
10.1002/chin.198701292
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
S. Ikegawa
中科院分区：
文献类型：
--
作者：
M. Thoma;R. Mahara;H. Takeshita;T. Kurosawa;S. Ikegawa
以相应的胆汁酸甲酯（1a-d）为原料合成了1β-羟基化石胆酸（10a）、去氧胆酸（10 b）、鹅去氧胆酸（10 c）和胆酸（10 d）。3-氧代胆汁酸酯（2a-d）经2，4-二溴代物（3a，eg）用醋酸铬还原脱溴，再用碳酸锂-溴化锂脱溴化氢，得到Δ 1-不饱和酮（6a，eg），再用碱性过氧化氢氧化，得到1β-2β-环氧酮（7a，eg）。环氧化物（7a，eg）经还原裂解后，用硼氢化钠还原，得到1β，3α-二羟基化合物（9a，eg），水解后得到1β-羟基化胆汁酸（10a-d）。本文用气相色谱-质谱联用技术，在健康人和肾脏病患者尿中检出1β，3α，12α-三羟基-5 β-胆烷-24-酸（10 b）。从人胎粪中检出新的1β，3α，7α-三羟基-（10 c）和1β，3α，-7α，12α-四羟基-5 β-胆烷-24-酸（10 d）。
1β-Hydoxylated lithocholic (10a), deoxycholic (10b), chenodeoxycholic (10c) and cholic (10d) acids were synthesized from the corresponding bile acid methyl esters (1a-d) as starting materials. The Δ 1-unsaturated ketones (6a, eg) were prepard from the 3-oxo bile acid esters (2a-d) via reductive debromination of their 2, 4-dibromides (3a, eg) with chromous acetate and dehydrobromination with lithium carbonate-lithium bromide, and oxidized with alkaline hydrogen peroxide to give the 1β-2β-epoxyketones (7a, eg). Reductive cleavage of the epoxides (7a, eg) and subsequent reduction with sodium borohydride afforded the 1β, 3α-dihydroxy compounds (9a, eg), which were hydrolyzed to the 1β-hydroxylated bile acids (10a-d). 1β, 3α, 12α-Trihydroxy-5β-cholan-24-oic acid (10b) was identified in the urine of healthy men and patients with kidney disease by gas chrmatography-mass spectrometric analysis. Novel 1β, 3α, 7α-trihydroxy-(10c) and 1β, 3α,-7α, 12α-tetrahydroxy-5β-cholan-24-oic acids (10d) were detected in human meconium.