CAS: 474-25-9; (R)-4-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-Dihydroxy-10,13-Dimethylhexadecahydro-1H-Cyclopenta[a]Phenanthren-17-yl)Pentanoic Acid

上下游产品

3,7-diket°Cholanic acid methyl 3α,7α-diacetoxy-12-one-5β-cholest-24-carboxylate 7-Ketolith°Cholic acid sodium ethanolatebis(3α-phenylsulfonyloxy-5β-cholansaeure-7α-yl)diester 5β-cholanic acid-3α,7α-diol di-p-fluorobenzoate 5β-cholestane-3α,7α-diol 7-Ketolith°Cholic acid

胆酸置于吡啶,Chromium(Vi) Oxide体系中,化学反应生成 鹅去氧胆酸
参考文献:P450 单加氧酶的工程区域选择性能够通过石胆酸的 7β-羟基化合成熊去氧胆酸
标题:P450 单加氧酶的工程区域选择性能够通过石胆酸的 7β-羟基化合成熊去氧胆酸
摘要:我们从抗生素链霉菌中改造了细胞色素 P450 单加氧酶 Cyp107D1 (Olep),用于石胆酸 (Lca) 的立体和区域选择性 7β-羟基化,产生熊去氧胆酸 (Udca).此前研究表明,Olep 可在 7β 位羟基化睾酮,但 Lca 仅在 6β 位羟基化,形成鼠脱氧胆酸 (Mdca).使用结构和 3Dm 分析以及分子对接来鉴定氨基酸残基 F84,S240 和 V291 作为特异性决定残基.丙氨酸扫描鉴定出 S240A 是产生 Udca 的变体.使用 Udca 比色测定法筛选基于这些位置的合成"小而智能"文库.我们鉴定了一种几乎完美的区域和立体选择性三重突变体(f84Q/s240A/v291G),其产生的 Udca 水平比 S240A 变体高 10 倍.这种生物催化剂为从生物废品 Lca 中环保合成 Udca 开辟了新的可能性.
DOI:10.1002/anie.202012675

专利信息

专利号:US-2013261317-A1
优先权日:2010-09-27
标题 :Methods for preparing synthetic bile acids and compositions comprising the same
发明人：MORIARTY ROBERT M; RAO PHOTON
权利人:MORIARTY ROBERT M; RAO PHOTON; KYTHERA BIOPHARMACEUTICALS INC
摘要:This invention relates generally to methods for preparing certain bile acids from non-mammalian sourced starting materials as well as to synthetic bile acids and compositions comprising such acids wherein the acids are characterized by a different C 14 population than naturally occurring bile acids as well as being free from any mammalian pathogens. This invention is also directed to the synthesis of intermediates useful in the synthesis of such bile acids. Accordingly, the C ring of the steroidal scaffold is oxidized to provide a synthetic route and intermediates to DCA. This invention also provides synthetic methods for preparing deoxycholic acid or a salt thereof starting from aromatic steroids such as estrogen, equilenin, and derivatives thereof. This invention is also directed to intermediates such as 12-oxo or delta-9,11-ene steroids as well as novel processes for their preparation. In preferred embodiments, bile acids are provided herein which have substituents on the B-ring and/or D-ring side chain and optionally on the hydroxy group of the A-ring.

专利号:US-7671085-B2
优先权日:2002-11-15
标 题 :Non-steroidal farnesoid X receptor modulators and methods for the use thereof
发明人：DOWNES MICHAEL R; EVANS RONALD M
权利人:SALK INST FOR BIOLOGICAL STUDI
摘要:The efficient regulation of cholesterol synthesis, metabolism, acquisition, and transport is an essential component of lipid homeostasis. The farnesoid X receptor (FXR) is a transcriptional sensor for bile acids, the primary product of cholesterol metabolism. Accordingly, the development of potent, selective, small molecule agonists, partial agonists, and antagonists of FXR would be an important step in further deconvoluting FXR physiology. In accordance with the present invention, the identification of novel potent FXR activators is described. Two derivatives of invention compounds, bearing stilbene or biaryl moieties, contain members that are the most potent FXR agonists reported to date in cell-based assays. These compounds are useful as chemical tools to further define the physiological role of FXR as well as therapeutic leads for the treatment of diseases linked to cholesterol, bile acids and their metabolism and homeostasis.