tert-butyl 3-(((2S,3R)-2-(benzyloxycarbonyl)-1-((S)-1-phenylethyl)pyrrolidin-3-yl)methyl)-1H-indole-1-carboxylate | 1048039-40-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 3-(((2S,3R)-2-(benzyloxycarbonyl)-1-((S)-1-phenylethyl)pyrrolidin-3-yl)methyl)-1H-indole-1-carboxylate
• 英文别名: tert-butyl 3-[[(2S,3R)-1-[(1S)-1-phenylethyl]-2-phenylmethoxycarbonylpyrrolidin-3-yl]methyl]indole-1-carboxylate
• CAS: 1048039-40-2
• 化学式: C₃₄H₃₈N₂O₄
• 分子量: 538.687
• InChiKey: QIUNUHKWJLXDFB-OIZHIJAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(((2S,3R)-2-(benzyloxycarbonyl)-1-((S)-1-phenylethyl)pyrrolidin-3-yl)methyl)-1H-indole-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、500.01 kPa 条件下， 反应 172.0h， 生成 (2S,3R)-3-((1H-indol-3-yl)methyl)-1-(2-naphthoyl)pyrrolidine-2-carboxylic acid trifluoroacetic acid
  参考文献：
  名称：

  Synthesis and Evaluation of Analogues of N-Phthaloyl-l-tryptophan (RG108) as Inhibitors of DNA Methyltransferase 1

  摘要：

  DNA methyltransferases (DNMT) are promising drug targets in cancer provided that new, more specific, and chemically stable inhibitors are discovered. Among the non-nucleoside DNMT inhibitors, N-phthaloyl-L-tryptophan 1 (RG108) was first identified as inhibitor of DNMT1. Here, 1 analogues were synthesized to understand its interaction with DNMT. The indole, carboxylate, and phthalimide moieties were modified. Homologated and conformationally constrained analogues were prepared. The latter were synthesized from prolinohomotryptophan derivatives through a methodology based amino-zinc-ene-enolate cyclization. All compounds were tested for their ability to inhibit DNMT1 in vitro. Among them, constrained compounds 16-18 and NPys derivatives 10-11 were found to be at least 10-fold more potent than the reference compound. The cytotoxicity on the tumor, DU145 cell line of the most potent inhibitors was correlated to their inhibitory potency. Finally, docking studies were conducted in order to understand their binding mode. This study provides insights for the design of the next-generation of DNMT inhibitors.

  DOI：

  10.1021/jm401419p
• 作为产物：
  描述：

  1-Boc-3-碘吲哚 、 (S)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate 在 palladium diacetate lithium diisopropyl amide 、 zinc dibromide 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 以60%的产率得到tert-butyl 3-(((2S,3R)-2-(benzyloxycarbonyl)-1-((S)-1-phenylethyl)pyrrolidin-3-yl)methyl)-1H-indole-1-carboxylate
  参考文献：
  名称：

  氨基-锌-烯-烯酸酯环化：短距离获得顺式3取代的脯氨酰-高色氨酸衍生物。

  摘要：

  脯氨酸嵌合体是用于药物化学和/或生物学应用的有用工具。顺式-3-取代的脯氨酸的不对称合成可通过氨基-锌-烯-烯酸酯环化，然后对环状锌中间体进行重金属化以进一步官能化来轻松实现。通过锌中间体与吲哚环的Negishi交叉偶联来实现脯氨酰-高色氨酸衍生物的合成。需要使用衍生自Fu的[（t-Bu3）PH] -BF4的Pd催化剂，以避免不希望的β-氢化物消除。获得易于用于肽合成的光学纯和正交保护的化合物。

  DOI：

  10.1021/jo801006a