17,19-di-O-ethyl-17-O-demethylgeldanamycin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 17,19-di-O-ethyl-17-O-demethylgeldanamycin
• 英文别名: [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19,21-diethoxy-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate
• 化学式: C₃₂H₄₆N₂O₁₀
• 分子量: 618.725
• InChiKey: PQYLCHCTBXODCV-IJZSZPJDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  173
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  sodium ethanolate 、 格尔德霉素 以 乙醇 、 二甲基亚砜 为溶剂， 反应 16.0h， 以15%的产率得到17,19-di-O-ethyl-17-O-demethylgeldanamycin
  参考文献：
  名称：

  Geldanamycin derivatives and neuroprotective effect on cultured P19-derived neurons

  摘要：

  Geldanamycin (1), an antifungal and anticancer ansamycin, was reported as a neurotrophic and neuroprotective substance against antineoplastic drugs, pactitaxel, vincristine, and cisplatin, on cultured dorsal root ganglion neurons from chick embryos. In this study, 1 in a large quantity, together with a known 17-O-demethylgeldanamycin (2), and a new 17-O-demethylgeldanamycin hydroquinone (3) were obtained from a mangrove Streptomyces sp. A series of O-alkyl and N-alkyl derivatives of 1 were prepared by modification of C-17 and/or C-19 on the quinone ring and were evaluated for in vitro activity against P19-derived neurons. Compound 1 and 19-O-methylgeldanamycin (7) at a very low dose (1 nM) enhanced survival and neurite outgrowth of P19-derived neurons and prevented neurotoxicity of paclitaxel and vinblastine. Compound 7, possessing the lowest cytotoxicity and neurotoxicity, is serving as the most promising candidate in neurodegenerative therapy against neurotoxic anticancer drugs. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.041

文献信息

• Geldanamycin derivatives and neuroprotective effect on cultured P19-derived neurons
  作者：Sarin Tadtong、Duangdeun Meksuriyen、Somboon Tanasupawat、Minoru Isobe、Khanit Suwanborirux

  DOI：10.1016/j.bmcl.2006.12.041

  日期：2007.5

  Geldanamycin (1), an antifungal and anticancer ansamycin, was reported as a neurotrophic and neuroprotective substance against antineoplastic drugs, pactitaxel, vincristine, and cisplatin, on cultured dorsal root ganglion neurons from chick embryos. In this study, 1 in a large quantity, together with a known 17-O-demethylgeldanamycin (2), and a new 17-O-demethylgeldanamycin hydroquinone (3) were obtained from a mangrove Streptomyces sp. A series of O-alkyl and N-alkyl derivatives of 1 were prepared by modification of C-17 and/or C-19 on the quinone ring and were evaluated for in vitro activity against P19-derived neurons. Compound 1 and 19-O-methylgeldanamycin (7) at a very low dose (1 nM) enhanced survival and neurite outgrowth of P19-derived neurons and prevented neurotoxicity of paclitaxel and vinblastine. Compound 7, possessing the lowest cytotoxicity and neurotoxicity, is serving as the most promising candidate in neurodegenerative therapy against neurotoxic anticancer drugs. (c) 2006 Elsevier Ltd. All rights reserved.