用猪去氧胆酸立体选择性合成脑甾醇的新方法

目的 探讨立体选择性合成脑甾醇的新方法.方法 以猪去氧胆酸为原料,经甲酯化、还原、Wittig反应、Sharpless不对称双羟化等9步反应合成脑甾醇,其中以乙酰链甾醇为关键中间体,以Sharpless不对称双羟化反应为关键步骤.结果 以52％的总收率、97％ de的立体选择性合成脑甾醇,其结构用质谱(MS)、核磁共振氢谱(1HNMR)、核磁共振碳谱(13CNMR)、红外光谱(IR)和元素分析等证实.结论 新的合成方法立体选择性高、收率高、每个中间体均为晶体易于重结晶纯化,可用于大量合成脑甾醇.     

Effect of raloxifene and hormone therapy on serum markers of brain and whole-body cholesterol metabolism in postmenopausal women

OBJECTIVE: To compare the 2-year effects of raloxifene (Rlx) with oral postmenopausal hormone therapy (HT) on serum markers of brain and whole-body cholesterol metabolism. METHODS: In a randomized, double-blind, placebo-controlled trial, 95 healthy, non-hysterectomized, early postmenopausal women received either daily Rlx 60 mg (n = 24), Rlx 150 mg (n = 23), HT (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 2.5 mg; n = 24), or placebo (n = 24). Fasting blood samples were collected at baseline and after 6, 12, and 24 months of treatment for measurement of serum concentrations of cholesterol by means of gas-liquid chromatography; 24S-hydroxycholesterol (cerebrosterol), lathosterol, and the plant sterol campesterol by means of gas-liquid chromatography-mass spectrometry. The analyses were performed retrospectively from serum samples stored at -70 degrees C for 5 years. RESULTS: Twenty-four months of treatment with raloxifene 150 mg was associated with a significant reduction in serum cholesterol concentrations (-10%, P = 0.007). The ratio of 24S-hydroxycholesterol to cholesterol, a serum marker of brain cholesterol metabolism, showed a significant increase after 6 and 12 months with raloxifene 150 mg but not after 24 months (P = 0.001). The ratio of lathosterol to cholesterol, a marker of whole-body cholesterol synthesis, increased with raloxifene 60 mg (P = 0.163), raloxifene 150 mg (P < 0.001), as well as with HT (P = 0.005). The ratio of campesterol to cholesterol, a marker of cholesterol absorption rate, was significantly reduced with HT (P = 0.002). CONCLUSION: Two-year treatment with raloxifene or HT had no influence on brain cholesterol metabolism, while whole-body cholesterol synthesis, assessed by the ratio of lathosterol to cholesterol, increased during raloxifene and HT.