3-O-[N-(allyl)carbamoyl]betulinic acid | 1187569-39-6

• 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: 3-O-[N-(allyl)carbamoyl]betulinic acid
• 英文别名: (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-9-(prop-2-enylcarbamoyloxy)-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylic acid
• CAS: 1187569-39-6
• 化学式: C₃₄H₅₃NO₄
• 分子量: 539.799
• InChiKey: LQJHUIYCGAWSTG-WVRTZRCQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  白桦脂酸 、 3-异氰酸丙烯 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以53%的产率得到3-O-[N-(allyl)carbamoyl]betulinic acid
  参考文献：
  名称：

  Rational Design and Semisynthesis of Betulinic Acid Analogues as Potent Topoisomerase Inhibitors

  摘要：

  Chemical transformation studies were conducted on betulinic acid (1), a common plant-derived lupane-type triterpene. Eleven new rationally designed derivatives of 1 (2-5 and 7-13) were synthesized based on docking studies and tested for their topoisomerase I and II alpha inhibitory activity. Semisynthetic reactions targeted C-3, C-20, and C-28 in 1. Structures of the new compounds were confirmed by spectroscopic methods (1D and 2D NMR and MS). Compound 9, 3-O-[N-(phenylsulfonyl)carbamoyl-17 beta-N-(phenylsulfonyl)amide]betulinic acid, showed 1.5-fold the activity of CPT in a topoisomerase I DNA relaxation assay. Four out of 14 betulinic acid analogues (5, 9, 11, and 12) showed 1.5-fold the activity of etoposide in a topoisomerase II assay. The new analogues exhibited better cytotoxic activities against the human colon cancer cells SW948 and HCT-116 and the breast cancer cell line MDA-MB-231 compared to the parent (1). Betulinic acid (1) is a potential scaffold for the design of new topoisomerase I and II alpha inhibitors.

  DOI：

  10.1021/np900312u

文献信息

• Rational Design and Semisynthesis of Betulinic Acid Analogues as Potent Topoisomerase Inhibitors
  作者：Fatma M. Abdel Bar、Mohammad A. Khanfar、Ahmed Y. Elnagar、Hui Liu、Ahmed M. Zaghloul、Farid A. Badria、Paul W. Sylvester、Kadria F. Ahmad、Kevin P. Raisch、Khalid A. El Sayed

  DOI：10.1021/np900312u

  日期：2009.9.25

  Chemical transformation studies were conducted on betulinic acid (1), a common plant-derived lupane-type triterpene. Eleven new rationally designed derivatives of 1 (2-5 and 7-13) were synthesized based on docking studies and tested for their topoisomerase I and II alpha inhibitory activity. Semisynthetic reactions targeted C-3, C-20, and C-28 in 1. Structures of the new compounds were confirmed by spectroscopic methods (1D and 2D NMR and MS). Compound 9, 3-O-[N-(phenylsulfonyl)carbamoyl-17 beta-N-(phenylsulfonyl)amide]betulinic acid, showed 1.5-fold the activity of CPT in a topoisomerase I DNA relaxation assay. Four out of 14 betulinic acid analogues (5, 9, 11, and 12) showed 1.5-fold the activity of etoposide in a topoisomerase II assay. The new analogues exhibited better cytotoxic activities against the human colon cancer cells SW948 and HCT-116 and the breast cancer cell line MDA-MB-231 compared to the parent (1). Betulinic acid (1) is a potential scaffold for the design of new topoisomerase I and II alpha inhibitors.