20,29-dihydro-20,29-(dichloromethylene)betulin | 557075-83-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 20,29-dihydro-20,29-(dichloromethylene)betulin
• 英文别名: (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bS)-1-(2,2-dichloro-1-methylcyclopropyl)-3a-(hydroxymethyl)-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-9-ol
• CAS: 557075-83-9
• 化学式: C₃₁H₅₀Cl₂O₂
• 分子量: 525.643
• InChiKey: YJIGFZJTPGIDEV-IEFJETGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  20,29-dihydro-20,29-(dichloromethylene)betulin 在 chromium(VI) oxide 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 0.17h， 以61.2%的产率得到20,29-dihydro-20,29-dichloromethylenebetulonic acid
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Cyclopropane Derivatives of Betulinic and Betulonic Acids

  摘要：

  通过将二氯卡宾或二溴卡宾连接到白桦脂酸二乙酸酯的双键上，然后脱去羟基保护基，合成了新的环丙烷白桦脂酸衍生物。通过在叔丁醇中用锂处理20,29-二氢-20,29-二氯亚甲基白桦脂酸，获得了白桦脂酸环丙烷衍生物。这些化合物通过三氧化铬氧化转化为相应的白桦脂酮酸衍生物。使用硼氢化钠还原羰基则得到相应的白桦脂酸衍生物。20,29-二氢-20,29-二氯亚甲基白桦脂酸对Colo 38和Bro系人类黑色素瘤以及CaOv系人类卵巢癌（IC50 10 μM）显示出最强的细胞毒性。20,29-二氢-20,29-二溴亚甲基白桦脂酸在10 μM浓度下几乎抑制Bro黑色素瘤细胞系和CaOv癌细胞系生长50%。其他白桦脂酸和白桦脂酮酸衍生物对所有三种癌细胞系在高于10 μM的浓度下均有活性。

  DOI：

  10.1007/s11171-005-0039-z
• 作为产物：
  描述：

  3β,28-diacetoxy-20,29-dichloromethanolupane 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 17.0h， 以3.50 g的产率得到20,29-dihydro-20,29-(dichloromethylene)betulin
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Cyclopropane Derivatives of Betulinic and Betulonic Acids

  摘要：

  通过将二氯卡宾或二溴卡宾连接到白桦脂酸二乙酸酯的双键上，然后脱去羟基保护基，合成了新的环丙烷白桦脂酸衍生物。通过在叔丁醇中用锂处理20,29-二氢-20,29-二氯亚甲基白桦脂酸，获得了白桦脂酸环丙烷衍生物。这些化合物通过三氧化铬氧化转化为相应的白桦脂酮酸衍生物。使用硼氢化钠还原羰基则得到相应的白桦脂酸衍生物。20,29-二氢-20,29-二氯亚甲基白桦脂酸对Colo 38和Bro系人类黑色素瘤以及CaOv系人类卵巢癌（IC50 10 μM）显示出最强的细胞毒性。20,29-二氢-20,29-二溴亚甲基白桦脂酸在10 μM浓度下几乎抑制Bro黑色素瘤细胞系和CaOv癌细胞系生长50%。其他白桦脂酸和白桦脂酮酸衍生物对所有三种癌细胞系在高于10 μM的浓度下均有活性。

  DOI：

  10.1007/s11171-005-0039-z

文献信息

• Cyclopropanation of betulin and its diacetate with dihalocarbenes
  作者：N. G. Komissarova、N. G. Belenkova、O. V. Shitikova、L. V. Spirikhin、M. S. Yunusov

  DOI：10.1007/s11178-005-0041-1

  日期：2004.10

  Reactions of betulin, its diacetate, and 17-acetoxy-28-norlupan-3-one with dichlorocarbene generated from chloroform follow the [1 + 2]-cycloaddition pattern leading to the corresponding adducts in moderate to quantitative yield. In the reaction with betulin, [1 + 2]-cycloaddition is accompanied by dichlorocarbene attack on the primary hydroxy group to give the corresponding halogen derivative and formate. The addition of dichlorocarbene to betulin is strictly stereoselective, while the reaction with betulin diacetate affords a mixture of two diastereoisomers at a ratio of 95 : 5. The reaction of betulin diacetate with dibromocarbene yields dibromocyclopropane derivative which can be converted into the the corresponding diol.

  从氯仿生成的二氯碳烯与贝图林、其二乙酰酸酯和17-乙酰氧基-28-去氢化-3-酮的反应遵循[1 + 2]-环加成模式，生成相应的加合物，其产率为中等至定量。在与贝图林的反应中，[1 + 2]-环加成伴随着二氯碳烯对初级羟基的攻击，生成相应的卤素衍生物和甲酸酯。二氯碳烯与贝图林的加成是严格的立体选择性，而与贝图林二乙酰酸酯的反应则生成两种diastereoisomer的混合物，比例为95:5。贝图林二乙酰酸酯与二溴碳烯的反应产生二溴环丙烷衍生物，该衍生物可以转化为相应的二醇。
• Selective inhibition of the interaction of C1q with immunoglobulins and the classical pathway of complement activation by steroids and triterpenoids sulfates
  作者：Svetlana Bureeva、Julian Andia-Pravdivy、Andrey Symon、Anna Bichucher、Vera Moskaleva、Vladimir Popenko、Alexey Shpak、Vitaly Shvets、Leonid Kozlov、Alexander Kaplun

  DOI：10.1016/j.bmc.2007.03.002

  日期：2007.5

  Since undesirable activation of the complement system through the classical pathway is associated with tissue damage and other pathologic proinflammatory consequences at ischemia/reperfusion injury, autoimmune diseases, and rejection of allo-and xenografts, creation of selective inhibitors of the classical pathway leaving the alternative pathway intact is of great importance. Classical pathway is triggered by binding of its recognizing unit, protein Clq, to a number of targets like antibodies, pentraxins, apoptotic cells, and others. In order to obtain inhibitors blocking the first step of the classical cascade, synthesis of sulfates of steroids (Delta(5)-3 beta-hydroxycholenic, Delta(5)-3 beta-hydroxyetiocholenic, deoxycholic, and cholic acids) and triterpenoids (betulin, 20,29-dihydro-20,29-dichloromethylenbetulin, betulinic, Ursolic, and oleanolic acids) has been performed. Testing of the compounds in classical pathway inhibition assay has displayed derivatives of triterpenoid betulin (betulin disulfate and betulinic acid sulfate) to be the most potent inhibitors. Further studies of the two compounds established that their activity to inhibit the classical pathway had been due to their capability to block the interaction of Clq with antibodies. Betulin disulfate and betulinic acid sulfate have shown weak inhibition of the alternative route of activation, what makes them promising inhibitors for the selective suppression of the classical complement pathway at the earliest possible level as well as perspective agents for blocking the interaction of Clq with its other targets. (c) 2007 Elsevier Ltd. All rights reserved.