methyl 3α-[(1,1-dimethylethyl)dimethylsilyloxy]-7-β-hydroxycholan-24-oate | 336099-77-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: methyl 3α-[(1,1-dimethylethyl)dimethylsilyloxy]-7-β-hydroxycholan-24-oate
• 英文别名: methyl 3α-tertbutyldimethylsilyloxy-7β-hydroxy-5β-cholan-24-oate
• CAS: 336099-77-5
• 化学式: C₃₁H₅₆O₄Si
• 分子量: 520.869
• InChiKey: XFDOVQPSOPEMRW-RZAQPKAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  36.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 3α-[(1,1-dimethylethyl)dimethylsilyloxy]-7-β-hydroxycholan-24-oate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 以94%的产率得到3α-tertbutyldimethylsilyloxy-7β-hydroxy-5β-cholan-24-oic acid
  参考文献：
  名称：

  Structural analysis and antitussive evaluation of five novel esters of verticinone and bile acids

  摘要：

  Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation, which consists of Snake Bile (Chinese name "Shedan") and Fritillariae Cirrhosae (Chinese name "Chuanbei"), is the most popular antitussive and expectorant formulation in Chinese communities. However, the clinical application of Shedan-Chuanbei powder is now stringently limited because of the shortage of the two crude medicinal materials, especially for the sake of animal protection. In addition, the inherent defects of the most of the complex of traditional Chinese medicine such as the indistinct basal phartnacodynamic materials and the difficulties in quality control had blocked them heading into the international medicinal market. So we attempted to seek new substitute for Shedan-Chuanbei powder for antitussive drugs. In order to gain some new compounds with better bioactivity and attenuated toxicity, we tried to combine two kinds of drugs through ester bond. Enlightened with "combination principle" in drug discovery, we synthesized five novel esters of verticinone and bile acids, both of which are the major bioactive components in Shedan-Chuanbei powder. We then evaluated the antitussive activity and the acute toxicity of the five ester-linked compounds. The five ester-linked Compounds had much more potent antitussive activity and expectorant activity than single bile acids at the same doses, and had equivalent antitussive activity and expectorant activity in comparison with about double moles dose of the monomer verticinone. Especially, cholic acid-verticinone ester had much more potent antitussive effects than the monomer verticinone or cholic acid at the same dose. A further acute toxicity study showed that the LD50 values of the five ester-linked compounds exceeded 3.5 g/kg by intraperitoneal injection in mice. Based on the studies of pharmacology and acute toxicity, the five ester-linked compounds have synergic pharmacodynamic action and attenuated toxicity compared with single verticinone and single bile acids. (C) 2008 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2008.12.007
• 作为产物：
  描述：

  methyl 3α-[(1,1-dimethylethyl)dimethylsilyloxy]-7-β-nitrosyloxycholan-24-oate 生成 methyl 3α-[(1,1-dimethylethyl)dimethylsilyloxy]-7-β-hydroxycholan-24-oate
  参考文献：
  名称：

  First total synthesis of xestobergsterol A and active structural analogues of the xestobergsterols

  摘要：

  The novel pentacyclic polyhydroxylated sterol, xestobergsterol A la, a strong inhibitor of histamine release from rat mast cells induced by anti-IgE, has been synthesized in 24 steps and good overall yield From stigmasterol 7. The Breslow remote functionalization process has been extended to several more highly functionalized steroid derivatives, especially those with oxygen functionality in the B-ring. The key steps of the synthesis of xestobergsterol A la and its analogues, 7-deoxyxestobergsterol A Id and 16,23-seco-23-deoxyxestobergsterol A 73, are the Breslow remote functionalization of oxygenated steroids and for compounds la and Id, a novel base-catalyzed epimerization-aldol condensation of a dione to give the desired CD-cis ring structure of the xestobergsterols. Thus the known alcohol 75, prepared from stigmasterol 7, was taken to the tetraacetate 107 which was then converted via a Breslow remote functionalization into the alkene aldehyde 114 which was transformed in 5 steps to xestobergsterol A la. Testing of the synthetic materials showed that the two analogues, 7-deoxyxestobergsterol A Ib and 16,23-seco-23-deoxyxestobergsterol A 73, are also potent inhibitors of histamine release with ICS, values (IC50 500 nM and 750 nM, respectively) being only 1015 times less than that of xestobergsterol A itself (50 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)01086-3

文献信息

• [EN] FLUORINATED AND ALKYLATED BILE ACIDS<br/>[FR] ACIDES BILIAIRES FLUORÉS ET ALKYLÉS
  申请人：METSELEX INC

  公开号：WO2016145216A1

  公开（公告）日：2016-09-15

  The present invention relates to fluorinated and alkylated bile acids.

  本发明涉及氟化和烷基化胆酸。
• Bile acids serve as endogenous antagonists of the Leukemia inhibitory factor (LIF) receptor in oncogenesis
  作者：Cristina Di Giorgio、Elva Morretta、Antonio Lupia、Rachele Bellini、Carmen Massa、Ginevra Urbani、Martina Bordoni、Silvia Marchianò、Ginevra Lachi、Pasquale Rapacciuolo、Claudia Finamore、Valentina Sepe、Maria Chiara Monti、Federica Moraca、Nicola Natalizi、Luigina Graziosi、Eleonora Distrutti、Michele Biagioli、Bruno Catalanotti、Annibale Donini、Angela Zampella、Stefano Fiorucci

  DOI：10.1016/j.bcp.2024.116134

  日期：2024.5

  metabolism and the intestinal microbiota. Here we demonstrated that bile acids serve as endogenous antagonist to LIFR in oncogenesis. The tissue characterization of bile acids content in non-cancer and cancer biopsy pairs from gastric adenocarcinomas (GC) demonstrated that bile acids accumulate within cancer tissues, with glyco-deoxycholic acid (GDCA) functioning as negative regulator of LIFR expression.

  白血病抑制因子 （LIF） 是白细胞介素 （IL）-6 细胞因子家族的成员，参与免疫调节、形态发生和肿瘤发生。在癌组织中，LIF 结合由 LIFRβ 亚基和糖蛋白 （gp） 形成的异二聚体受体 （LIFR）130，促进上皮间充质转化和细胞生长。胆汁酸是在宿主代谢和肠道微生物群界面处产生的胆固醇代谢物。在这里，我们证明了胆汁酸在肿瘤发生中是 LIFR 的内源性拮抗剂。胃腺癌 （GC） 非癌和癌症活检对中胆汁酸含量的组织表征表明，胆汁酸在癌组织内积累，其中糖脱氧胆酸 （GDCA） 作为 LIFR 表达的负调节因子。在来自 GC 患者的患者来源类器官 （hPDO） 中，GDCA 可逆转 LIF 诱导的干性和增殖。总之，我们已经确定次级胆汁酸是 LIFR 的第一个内源性拮抗剂，支持在 LIF 介导的肿瘤发生中开发基于胆汁酸的疗法。