(2R,6R)-2-(digitoxigenoxy)-3,6-dihydro-6-methyl-2H-pyran | 912454-91-2

• 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: (2R,6R)-2-(digitoxigenoxy)-3,6-dihydro-6-methyl-2H-pyran
• 英文别名: cis-3,6-dihydro-6-methyl-2-(digitoxigenoxy)-2H-pyran；3-[(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-3-[[(2R,6R)-6-methyl-3,6-dihydro-2H-pyran-2-yl]oxy]-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
• CAS: 912454-91-2
• 化学式: C₂₉H₄₂O₅
• 分子量: 470.649
• InChiKey: FEKFMSRTJINZSK-FCOBINHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,6R)-2-(digitoxigenoxy)-3,6-dihydro-6-methyl-2H-pyran 在 tris(dibenzylideneacetone)dipalladium (0) sodium tetrahydroborate 、 四氧化锇 、 cerium(III) chloride 、 对甲苯磺酸 、 N-甲基吗啉氧化物 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 丙酮 、 叔丁醇 为溶剂， 反应 15.0h， 生成 digitoxigen 3-O-acetyl-2,6-dideoxy-4-O-((2'R,5'S,6'R)-5',6'-dihydro-5'-hydroxy-6'-methyl-2H-pyran-2'-yl)-β-D-ribo-hexopyranoside
  参考文献：
  名称：

  通过钯催化的糖基化从洋地黄毒苷立体选择性合成洋地黄毒苷和洋地黄毒苷单和双指氧苷。

  摘要：

  已经开发了收敛和立体控制的三糖天然产物洋地黄毒苷的途径。该路线适合于制备洋地黄毒苷和双洋地黄毒苷。该途径的特征是钯催化的糖基化反应，还原性1,3-移位，非对映选择性二羟基化和区域选择性保护的迭代应用。天然产物洋地黄毒苷从洋地黄毒苷2和吡喃酮8a开始共分15步，或从非手性酰基呋喃开始共18步。

  DOI：

  10.1021/ol061683b
• 作为产物：
  描述：

  (2R,6R)-3,6-dihydro-2-methyl-6-(digitoxigenoxy)-2H-pyran-3-ol 在 2-硝基苯磺酰肼 N-甲基吗啉 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以80%的产率得到(2R,6R)-2-(digitoxigenoxy)-3,6-dihydro-6-methyl-2H-pyran
  参考文献：
  名称：

  从头开始的2-Deoxy-β-糖苷方法：地高糖和Digitoxin 1的不对称合成

  摘要：

  已经开发出了高度对映选择性和直接的途径来制备三糖天然产物地高糖和洋地黄毒苷。该方法的关键是钯催化糖基化反应，还原性1,3-移位，非对映选择性二羟基化和区域选择性保护的迭代应用。天然产物digoxose的第一全合成是在非手性从2- acylfuran 19个总步骤完成，和洋地黄毒苷在15个步骤塑成从洋地黄毒苷开始2和吡喃酮8 β。这种灵活的合成策略还允许制备地高糖和洋地黄毒苷的单糖和二糖类似物。

  DOI：

  10.1021/jo062534+

文献信息

• Stereochemical Survey of Digitoxin Monosaccharides
  作者：Hua-Yu Leo Wang、Wenjun Xin、Maoquan Zhou、Todd A. Stueckle、Yon Rojanasakul、George A. O'Doherty

  DOI：10.1021/ml100219d

  日期：2011.1.13

  A stereochemically diverse array of monosaccharide analogues of the trisaccharide-based cardiac glycoside natural product digitoxin has been synthesized using a de novo asymmetric approach. The analogues were tested for cytotoxicity against nonsmall cell human lung cancer cells (NCI-H460). The results were compared with digitoxin and its aglycone digitoxigenin. Three novel digitoxin monosaccharide analogues with beta-D-digitoxose, alpha-L-rhamnose, and alpha-L-amicetose sugar moieties showed excellent selectivity and activity. Further investigation revealed that digitoxin alpha-L-rhamnose and alpha-L-amicetose analogues displayed similar anti-proliferation effects but with at least 5-fold greater potency in apoptosis induction than digitoxin against NCI-H460. This study demonstrates the ability to improve the digitoxin anticancer activity by modification of the stereochemistry and substitution of the carbohydrate moiety of this known cardiac drug.
• 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.