3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-3-(methoxyamino)-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one | 868753-49-5

• 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: 3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-3-(methoxyamino)-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
• CAS: 868753-49-5
• 化学式: C₂₄H₃₇NO₄
• 分子量: 403.562
• InChiKey: UJTKKPSEKYHORZ-BMPKRDENSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-3-(methoxyamino)-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one 、 2-deoxy-2-azido-D-xylospyranose 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以11%的产率得到
  参考文献：
  名称：

  Influence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity

  摘要：

  The synthesis of a set of digitoxigenin neogluco/xylosides and corresponding study of their anticancer SAR revealed sugar amine regiochemistry has a dramatic effect upon activity. Specifically, this study noted sugar 3-amino followed 1 by 4-amino-substitution to be most advantageous where the solvent accessibility of the appended amine within neoglycoside-Na+,K+-ATPase docked models correlated with increased anticancer potency. This study presents a preliminary model for potential further warhead optimization in the context of antibody-directed steroidal glycosides and extends the demonstrated compatibility of aminosugars in the context of neoglycosylation.

  DOI：

  10.1021/acsmedchemlett.5b00120
• 作为产物：
  描述：

  4-((5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-3-(methoxyimino)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)furan-2(5H)-one 在 盐酸 、 硼烷-叔丁基胺 、 水 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 2.5h， 以44%的产率得到4-((3R,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-3-(methoxyamino)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)furan-2(5H)-one
  参考文献：
  名称：

  [EN] NEOGLYCORANDOMIZATION AND DIGITOXIN ANALOGS
  [FR] ALEATOIRISATION DES NEOGLYCOSIDES ET ANALOGUES DE LA DIGITOXINE

  摘要：

  本发明提供了一种生产具有增强理想性能和减少副作用的化合物库的方法，以及通过这些方法生产的化合物。在优选实施例中，本发明的方法使用一种通用的化学糖基化方法，该方法采用还原糖，无需保护或激活。在优选实施例中，本发明提供了一种新糖苷地高辛类似物库，其中包括对人类癌细胞具有显著增强的细胞毒性活性和肿瘤特异性的化合物，但在人类细胞系中对Na+/K+-ATPase的抑制作用较地高辛要弱。

  公开号：

  WO2006002381A1

文献信息

• A Direct Comparison of the Anticancer Activities of Digitoxin MeON-Neoglycosides and <i>O</i>-Glycosides
  作者：Anand Krishnan V. Iyer、Maoquan Zhou、Neelam Azad、Hosam Elbaz、Leo Wang、Derek K. Rogalsky、Yon Rojanasakul、George A. O'Doherty、Joseph M. Langenhan

  DOI：10.1021/ml1000933

  日期：2010.10.14

  Digitoxin is a cardiac glycoside currently being investigated for potential use in oncology; however, an investigation of anticancer activity as a function, of oligosaccharide chain length has not yet been performed. We generated mono-, di-, and tri-O-digitoxoside derivatives, of digitoxin and compared their activities to the corresponding MeON-neoglycosides. Both classes of cardenolide derivatives display comparable oligosaccharide chain length-dependent cytotoxicity toward human cancer cell lines. Further investigation revealed that both classes of compounds induce caspase-9-mediated apoptosis in non-small cell lung cancer cells (NCI-H460). Because O-glycosides and MeON-neoglycosides share a similar mode of action, the convenience of MeON-neoglycosylation could be exploited in future SAR work to rapidly survey large numbers of carbohydrates to prioritize selected O-glycoside candidates for traditional synthesis.
• Modifying the glycosidic linkage in digitoxin analogs provides selective cytotoxins
  作者：Joseph M. Langenhan、Jeffery M. Engle、Lauren K. Slevin、Lindsay R. Fay、Ryan W. Lucker、Kyle R. Smith、Matthew M. Endo

  DOI：10.1016/j.bmcl.2007.11.058

  日期：2008.1

  A chemoselective reaction between oxyamines and unprotected, unactivated reducing sugars was used to construct for the first time a panel of linkage-diversified neoglycosides. This panel of digitoxin analogs included potent and selective tumor cytotoxins; cytotoxicity was dependent on the structure of the glycosidic linkage. These results validate linkage diversification through neoglycosylation as a unique and simple strategy to powerfully complement existing methods for the optimization of glycoconjugates. (c) 2007 Elsevier Ltd. All rights reserved.