N^2'-deacetyl-N^2'-[2-(methyldithio)-1-oxopropyl]maytansine

• 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: N^2'-deacetyl-N^2'-[2-(methyldithio)-1-oxopropyl]maytansine
• 英文别名: [(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2R)-2-[methyl-[3-(methyldisulfanyl)propanoyl]amino]propanoate
• 化学式: C₃₆H₅₀ClN₃O₁₀S₂
• 分子量: 784.392
• InChiKey: ZLUUPZXOPGORNG-UNXOEUSJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  52
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  207
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N^2'-deacetyl-N^2'-[2-(methyldithio)-1-oxopropyl]maytansine 在 乙二胺四乙酸 、 1,4-二巯基-2,3-丁二醇 作用下， 以 甲醇 、 phosphate buffer 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 D-N^2'-deacetyl-N^2'-(3-mercapto-1-oxopropyl)maytansine
  参考文献：
  名称：

  Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer

  摘要：

  Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.

  DOI：

  10.1021/jm060319f
• 作为产物：
  描述：

  (S)-2-(n-甲基-3-(甲基二磺酰基)丙酰胺)丙酸 、 maytansinol 在 N,N'-二环己基碳二亚胺 、 zinc(II) chloride 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.0h， 以32%的产率得到N^2'-deacetyl-N^2'-[3-(methyldithio)-1-oxopropyl]maytansine
  参考文献：
  名称：

  Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer

  摘要：

  Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.

  DOI：

  10.1021/jm060319f

文献信息

• [EN] PREPARATION OF MAYTANSINOID ESTERS<br/>[FR] PRÉPARATION D'ESTERS DE MAYTANSINOÏDE
  申请人：BIO THERA SOLUTIONS LTD

  公开号：WO2014094354A1

  公开（公告）日：2014-06-26

  Provided are efficient methods for direct coupling of a maytansinoid with a carboxylic acid to prepare a maytansinoid C-3 ester in high yield using a rare earth metal-based or trifluoromethanesulfonate-based Lewis acid catalyst and a base together with a coupling reagent. Also provided are compositions used in such methods.

  提供了一种高效的方法，用稀土金属基或三氟甲磺酸盐基的路易斯酸催化剂和碱以及偶联试剂直接偶联马坦西酮与羧酸，以高收率制备马坦西酮C-3酯。还提供了在这种方法中使用的组合物。
• Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer
  作者：Wayne C. Widdison、Sharon D. Wilhelm、Emily E. Cavanagh、Kathleen R. Whiteman、Barbara A. Leece、Yelena Kovtun、Victor S. Goldmacher、Hongsheng Xie、Rita M. Steeves、Robert J. Lutz、Robert Zhao、Lintao Wang、Walter A. Blättler、Ravi V. J. Chari

  DOI：10.1021/jm060319f

  日期：2006.7.1

  Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.