penta-O-methyl-(+)-gallocathechin | 273931-30-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: penta-O-methyl-(+)-gallocathechin
• 英文别名: penta-O-methylgallocatechin；(2R,3S)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-ol；(2R)-5,7-Dimethoxy-2r-(3,4,5-trimethoxy-phenyl)-chroman-3t-ol；(2R,3S)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-3,4-dihydro-2H-chromen-3-ol
• CAS: 273931-30-9
• 化学式: C₂₀H₂₄O₇
• 分子量: 376.406
• InChiKey: XTGUWFUENAJQSX-IFXJQAMLSA-N

物化性质

• 沸点：
  536.3±50.0 °C(Predicted)
• 密度：
  1.220±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  藜芦酸 、 penta-O-methyl-(+)-gallocathechin 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以87.4%的产率得到(2R,3S)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl 3,4-dimethoxybenzoate
  参考文献：
  名称：

  Potent and Nontoxic Chemosensitizer of P-Glycoprotein-Mediated Multidrug Resistance in Cancer: Synthesis and Evaluation of Methylated Epigallocatechin, Gallocatechin, and Dihydromyricetin Derivatives

  摘要：

  We are interested in developing novel natural product-derived P-gp inhibitors to reverse cancer drug resistance. Here, we have synthesized 55 novel derivatives of methylated epigallocatechin (EGC), gallocatechin (GC), and dihydromyricetin (DHM). Three EGC derivatives (23, 35, and 36) and three GC derivatives (50, 51, and 53) are significantly better than epigallocatechin gallate (EGCG) with a relative fold (RF) ranging from 31.4 to 53.6. The effective concentration (EC50) of 23 and 51 ranges from 102 to 195 nM. Compounds 23 and 51 are noncytotoxic to fibroblasts with IC50 > 100 mu M. Compound 23 is specific for P-gp without modulating activity toward MITI or BCRP. Compounds 23 and 51 are non-P-gp substrates. Important pharmacophores for P-gp modulation were identified. In summary, methylated EGC and GC derivatives represent a new class of potent, specific, noncytotoxic, and nonsubstrate P-gp modulators.

  DOI：

  10.1021/acs.jmedchem.5b00085
• 作为产物：
  描述：

  (2R,3S)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)chroman-3-yl 3,4,5-trimethoxybenzoate 在 甲醇 、 potassium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 以87.1%的产率得到penta-O-methyl-(+)-gallocathechin
  参考文献：
  名称：

  Potent and Nontoxic Chemosensitizer of P-Glycoprotein-Mediated Multidrug Resistance in Cancer: Synthesis and Evaluation of Methylated Epigallocatechin, Gallocatechin, and Dihydromyricetin Derivatives

  摘要：

  We are interested in developing novel natural product-derived P-gp inhibitors to reverse cancer drug resistance. Here, we have synthesized 55 novel derivatives of methylated epigallocatechin (EGC), gallocatechin (GC), and dihydromyricetin (DHM). Three EGC derivatives (23, 35, and 36) and three GC derivatives (50, 51, and 53) are significantly better than epigallocatechin gallate (EGCG) with a relative fold (RF) ranging from 31.4 to 53.6. The effective concentration (EC50) of 23 and 51 ranges from 102 to 195 nM. Compounds 23 and 51 are noncytotoxic to fibroblasts with IC50 > 100 mu M. Compound 23 is specific for P-gp without modulating activity toward MITI or BCRP. Compounds 23 and 51 are non-P-gp substrates. Important pharmacophores for P-gp modulation were identified. In summary, methylated EGC and GC derivatives represent a new class of potent, specific, noncytotoxic, and nonsubstrate P-gp modulators.

  DOI：

  10.1021/acs.jmedchem.5b00085

文献信息

• Cronje, Annemarie; Steynberg, Jan P.; Brandt, E. Vincent, Journal of the Chemical Society. Perkin transactions I, 1993, p. 2467 - 2478
  作者：Cronje, Annemarie、Steynberg, Jan P.、Brandt, E. Vincent、Young, Desmond A.、Ferreira, Daneel

  DOI：——

  日期：——
• Mayer; Bauni, Justus Liebigs Annalen der Chemie, 1958, vol. 611, p. 264,267
  作者：Mayer、Bauni

  DOI：——

  日期：——
• Structure and synthesis of the first procassinidin dimers based on epicatechin, and gallo- and epigallo-catechin
  作者：Johan Coetzee、Lulama Mciteka、Elfranco Malan、Daneel Ferreira

  DOI：10.1016/s0031-9422(00)00017-0

  日期：2000.4

  The range of natural dimeric procassinidins is extended by identification of cassiaflavan-(4 alpha --> 8)-epicatechin, cassiaflavan-(4 alpha --> 8)-epigallocatechin, cassiaflavan-(4 beta --> 8)-epicatechin, cassiaflavan-(4 beta --> 8)-epigallocatechin, cassiaflavan-(4 beta --> 8)-gallocatechin, ent-cassiaflavan-(4 beta --> 8)-epicatechin and cassiaflavan-(4 alpha --> 6)-epicatechin in the bark of Cassia petersiana. Their structures and absolute configuration were confirmed by synthesis. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Potent and Nontoxic Chemosensitizer of P-Glycoprotein-Mediated Multidrug Resistance in Cancer: Synthesis and Evaluation of Methylated Epigallocatechin, Gallocatechin, and Dihydromyricetin Derivatives
  作者：Iris L. K. Wong、Bao-Chao Wang、Jian Yuan、Liang-Xing Duan、Zhen Liu、Tao Liu、Xue-Min Li、Xuesen Hu、Xiao-Yu Zhang、Tao Jiang、Sheng-Biao Wan、Larry M. C. Chow

  DOI：10.1021/acs.jmedchem.5b00085

  日期：2015.6.11

  We are interested in developing novel natural product-derived P-gp inhibitors to reverse cancer drug resistance. Here, we have synthesized 55 novel derivatives of methylated epigallocatechin (EGC), gallocatechin (GC), and dihydromyricetin (DHM). Three EGC derivatives (23, 35, and 36) and three GC derivatives (50, 51, and 53) are significantly better than epigallocatechin gallate (EGCG) with a relative fold (RF) ranging from 31.4 to 53.6. The effective concentration (EC50) of 23 and 51 ranges from 102 to 195 nM. Compounds 23 and 51 are noncytotoxic to fibroblasts with IC50 > 100 mu M. Compound 23 is specific for P-gp without modulating activity toward MITI or BCRP. Compounds 23 and 51 are non-P-gp substrates. Important pharmacophores for P-gp modulation were identified. In summary, methylated EGC and GC derivatives represent a new class of potent, specific, noncytotoxic, and nonsubstrate P-gp modulators.