Schroepfer G J, Parish E J, Kandutsch A A, Bowen S T, Quiocho F A
Department of Biochemistry, Rice University, Houston, Texas 77001.
Biochem Int. 1987 Aug;15(2):403-8.
Treatment of 3 beta-benzoyloxy-14 alpha,15 alpha-epoxy-5 alpha-cholest-7-ene with methyl magnesium iodide gave, as the major product, 15 beta-methyl-5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol. The product was characterized as the free sterol and in the form of its 3 beta-acetoxy and 3 beta-p-bromobenzoate derivatives. Unambiguous assignment of structure was based upon X-ray analysis of the latter derivative. 15 beta-Methyl-5 alpha,14 beta-cholest-7-ene-3 beta,15 alpha-diol was found to be a potent inhibitor of sterol synthesis in cultured mammalian cells. The 15 beta-methyl-3 beta,15 alpha-dihydroxysterol caused a 50% reduction of the level of HMG-CoA reductase activity and a 50% reduction in the incorporation of labeled acetate into digitonin-precipitable sterols in L cells at a concentration of 3.0 x 10(-6) M.
用甲基碘化镁处理3β-苯甲酰氧基-14α,15α-环氧-5α-胆甾-7-烯，得到的主要产物是15β-甲基-5α,14β-胆甾-7-烯-3β,15α-二醇。该产物被表征为游离甾醇及其3β-乙酰氧基和3β-对溴苯甲酸酯衍生物的形式。结构的明确归属基于对后一种衍生物的X射线分析。发现15β-甲基-5α,14β-胆甾-7-烯-3β,15α-二醇是培养的哺乳动物细胞中甾醇合成的有效抑制剂。在浓度为3.0×10⁻⁶ M时，15β-甲基-3β,15α-二羟基甾醇使L细胞中HMG-CoA还原酶活性水平降低50%，并使标记的乙酸掺入洋地黄皂苷可沉淀甾醇的量减少50%。
