美登素杂质 | 902768-55-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 中文名称: 美登素杂质
• 英文名称: N^2'-deacetyl-N^2'-[4-methyl-4-(methyldithio)-1-oxopentyl]-D-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-[4-methyl-4-(methyldisulfanyl)pentanoyl]amino]propanoate
• CAS: 902768-55-2
• 化学式: C₃₉H₅₆ClN₃O₁₀S₂
• 分子量: 826.473
• InChiKey: LTLNAIFGVAUBEJ-QLVIVZODSA-N

物化性质

• 熔点：
  165-167 °C
• 沸点：
  963.8±65.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  55
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 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：

  美登素杂质 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， 生成 D-N^2'-deacetyl-N^2'-(4-mercapto-4-methyl-1-oxopentyl)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：

  2,5-dioxopyrrolidin-1-yl 4-methyl-4-(methyldisulfanyl)pentanoate 在 三乙胺 、 N,N'-二环己基碳二亚胺 、 zinc(II) chloride 作用下， 以 乙二醇二甲醚 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 美登素杂质
  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

• Method for the preparation of maytansinoid esters
  申请人：Widdison C. Wayne

  公开号：US20060167245A1

  公开（公告）日：2006-07-27

  Improved processes for the preparation and purification of maytansinoid esters, especially thiol and disulfide-containing maytansinoids are described. In one aspect the process comprises a process of making a maytansinoid ester comprising forming an anion of maytansinol or a maytansinoid bearing a free C-3 hydroxyl moiety and reacting the anion with an activated carboxyl compound to thereby produce the maytansinoid ester.

  描述了用于制备和纯化美坦西酯类化合物的改进过程，特别是含有硫醇和二硫键的美坦西酯类化合物。在一个方面，该过程包括制备美坦西酯类化合物的过程，其中包括形成美坦西醇或带有游离C-3羟基的美坦西酯类化合物的阴离子，并将该阴离子与活化的羧基化合物反应，从而产生美坦西酯类化合物。
• 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.