4-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-4'-demethylepipodophyllotoxin | 144177-24-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-4'-demethylepipodophyllotoxin
• 英文别名: 4-O-(2’,3’,4’,6’-tetra-O-acetyl-α-D-glucopyranosyl)-4-demethylepipodophyllotoxin；[(2R,3R,4S,5R,6S)-6-[[(5S,5aR,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]oxy]-3,4,5-triacetyloxyoxan-2-yl]methyl acetate
• CAS: 144177-24-2
• 化学式: C₃₅H₃₈O₁₇
• 分子量: 730.677
• InChiKey: ZMFUAABNHDNWCY-CJQKZJOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  52
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  207
• 氢给体数：
  1
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  4-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-4'-demethylepipodophyllotoxin 在 甲醇 、 sodium methylate 作用下， 反应 2.0h， 以78%的产率得到4-O-(α-D-glucopyranosyl)-4'-demethylepipodophyllotoxin
  参考文献：
  名称：

  鬼臼毒素葡萄糖苷衍生物：合成、理化性质和细胞毒性

  摘要：

  Background: Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4 beta-triazolyl-podophyllotoxin glycosides show good anticancer activity, the peracetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied.Methods: A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 (leukemia), SMMC-7721 (hepatoma), A-549 (lung cancer), MCF-7 (breast cancer), and SW480 (colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure-activity relationship and the physicochemical property-anticancer activity relationship of these compounds.Results: Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27 +/- 0.21 to 11.37 +/- 0.52 mu M. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA < 20, ClogP > 2, MW > 700 Da, and RB > 10.Conclusion: We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents.

  DOI：

  10.2147/dddt.s215895
• 作为产物：
  描述：

  2,3,4,5-tetra-O-acetyl-D-glucopyranose 在 三氟化硼乙醚 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 4-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-4'-demethylepipodophyllotoxin
  参考文献：
  名称：

  Stereoselective glucosidation of podophyllum lignans. A new simple synthesis of etoposide

  摘要：

  DOI：

  10.1021/jo00067a071

文献信息

• A short and simple synthesis of the antitumor agent etoposide
  作者：Pietro Allevi、Mario Anastasia、Pierangela Ciuffreda、Anna Maria Sanvito、Peter Macdonald

  DOI：10.1016/s0040-4039(00)61297-2

  日期：1992.8

  the antitumor agent etoposide has been synthesized for the first time from unprotected 4'-demethylepipodophyllotoxin.