(R)-4-((3R,5R,8R,9S,10S,12S,13R,14S,17R)-12-Acetoxy-3-azido-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoic acid methyl ester | 198974-64-0

• 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: (R)-4-((3R,5R,8R,9S,10S,12S,13R,14S,17R)-12-Acetoxy-3-azido-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoic acid methyl ester
• CAS: 198974-64-0
• 化学式: C₂₇H₄₃N₃O₄
• 分子量: 473.656
• InChiKey: YLXVUHADAIQMAO-RFTNVYQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.46
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  101.36
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R)-4-((3R,5R,8R,9S,10S,12S,13R,14S,17R)-12-Acetoxy-3-azido-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoic acid methyl ester 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 以99%的产率得到(4R)-4-((3R,5R,10S,12S,13R,17R)-3-azido-12-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid
  参考文献：
  名称：

  Bile acid toxicity structure–activity relationships: Correlations between cell viability and lipophilicity in a panel of new and known bile acids using an oesophageal cell line (HET-1A)

  摘要：

  The molecular mechanisms and interactions underlying bile acid cytotoxicity are important to understand for intestinal and hepatic disease treatment and prevention and the design of bile acid-based therapeutics.Bile acid lipophilicity is believed to be an important cytotoxicity determinant but the relationship is not well characterized. In this study we prepared new azido and other lipophilic BAs and altogether assembled a panel of 37 BAs with good dispersion in lipophilicity as reflected in RPTLC R-Mw. The MTT cell viability assay was used to assess cytotoxicity over 24 h in the HET-1A cell line (oesophageal). RMw values inversely correlated with cell viability for the whole set (r(2) = 0.6) but this became more significant when non-acid compounds were excluded (r(2) = 0.82, n = 29). The association in more homologous subgroups was stronger still (r(2) > 0.96). None of the polar compounds were cytotoxic at 500 mu M, however, not all lipophilic BAs were cytotoxic. Notably, apart from the UDCA primary amide, lipophilic neutral derivatives of UDCA were not cytotoxic. Finally, CDCA, DCA and LagoDCA were prominent outliers being more toxic than predicted by R-Mw. In a hepatic carcinoma line, lipophilicity did not correlate with toxicity except for the common naturally occurring bile acids and their conjugates. There were other significant differences in toxicity between the two cell lines that suggest a possible basis for selective cytotoxicity. The study shows: (i) azido substitution in BAs imparts lipophilicity and toxicity depending on orientation and ionizability; (ii) there is an inverse correlation between R-Mw and toxicity that has good predictive value in homologous sets; (iii) lipophilicity is a necessary but apparently not sufficient characteristic for BA cytocidal activity to which it appears to be indirectly related. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.030
• 作为产物：
  描述：

  在 Zn(N₃)₂*Py₂ 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 生成 (R)-4-((3R,5R,8R,9S,10S,12S,13R,14S,17R)-12-Acetoxy-3-azido-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoic acid methyl ester
  参考文献：
  名称：

  含有类固醇假氨基酸的环肽中的β-环，γ-环和螺旋肽构象

  摘要：

  类固醇假氨基酸3ã-amino-5β-cholan-24- oicacid （2a），12ã-acetoxy-3ã-氨5β-cholan-24- oicacid （2b）和7ã，12ã-diacetoxy-3ã -amino-5β-cholan-24-oicacid（2c）被用作环状肽的骨架中的刚性间隔基cyclo（– 2a –Phe-Phe–）2（1a），cyclo（– 2b –Phe-Phe– ）2（1b）和cyclo（–2c-Phe-Phe–）2（1c）。在1a和1b的肽链中发现了均相的β环构象，而1c以α-螺旋和γ-环构象的混合物形式存在。构象的结构和均一性是通过几种NMR技术确定的，并得到分子动力学计算的支持。肽的构象取决于环状分子的两个大的亲脂性甾体部分的距离和吸引力。

  DOI：

  10.1002/hlca.19970800716