Chemical synthesis of 15-ketosterols and their inhibitions of cholesteryl ester transfer protein.
作者： Hong-Seok Kim , Sang Ho Oh , Dong-Il Kim , In-Chul Kim , Kyung-Hyun Cho
DOI: 10.1016/0968-0896(95)00025-C
关键词: Organic chemistry 、 Cholesterylester transfer protein 、 Chemical synthesis 、 Clemmensen reduction 、 Diosgenin 、 Hydrolysis 、 Cholesteryl ester 、 In vitro 、 Chemistry 、 Acceptor
摘要: Abstract Described herein are the chemical syntheses of 3β-hydroxy-5α-cholest-8(14)-en-15-one and 3β-hydroxy-5α-cholest-8(14), 16-dien-15-one from diosgenin examinations their ability to inhibit cholesteryl ester transfer protein (CETP). Clemmensen reduction gave cholest-5-ene-3β,16β,26-triol. Tosylation latter compound cholest-5-ene-3β,16β,26-triol 26-tosylate which, upon with LiAlH 4 , cholest-5-ene-3β,16β-diol. Hydrogenation-benzoylation 5α-cholest-3β,16β-diol 3β-benzoate followed by mesylation-elimination 5α-cholest-16-ene-3β-ol 3β-benzoate. Controlled oxidation CrO3-dimethylpyrazole 3β-hydroxy-5α,14α-cholest-16-en-15-one Oxidation Δ 16 -15-one SeO 2 3β-hydroxy-5α-cholest-8(14),16-dien-15-one along 3β-hydroxy-5α,14β-cholest-16-en-15-one Selective hydrogenation 8(14).16 -15-ketosteryl ester, base hydrolysis 3β-hydroxy-5α-cholest-8(14)-en-15-one. Hydrolysis in basic media 3β-hydroxy-5α-cholest-8(14),16-dien-15-one. The effects 15-ketosterols on CETP activity were studied vitro incubating donor (HDL), acceptor (LDL) human plasma as a source at 37 °C. 3β-Hydroxy-5α-cholest-8(14)-en-15-one was found be active supression levels plasma.
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