benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionylamino]-propionyloxy]-4-methylpentanoate | 219606-83-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionylamino]-propionyloxy]-4-methylpentanoate
• CAS: 219606-83-4
• 化学式: C₃₁H₄₂N₂O₈
• 分子量: 570.683
• InChiKey: AAWIVDFIZTWPBS-FTJBHMTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  41.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  129.26
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionylamino]-propionyloxy]-4-methylpentanoate 在 palladium hydroxide - carbon 4-二甲氨基吡啶 、 氢气 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  Total Synthesis of Cryptophycins-1, -3, -4, -24 (Arenastatin A), and -29, Cytotoxic Depsipeptides from Cyanobacteria of the Nostocaceae

  摘要：

  A convergent synthesis of cryptophycins has been developed in which (5S,GR)-5-hydroxy-6-methyl-8-phenylocta-2(E),7(E)-dienoic add (A) is coupled with an amino acid. segment (B). Two stereoselective routes to A are described, the first employing allylation of an alpha-homochiral aldehyde and the second using asymmetric crotylation of an achiral aldehyde to establish the two stereogenic centers present in a. The styryl moiety of A was attached either via Stille coupling or through a Wadsworth-Emmons condensation with diethyl benzylphosphonate. The amino acid subunit B was prepared from benzyl (2S)-2-hydroxyisocaproate by connection first to N-Boc-beta-alanine or its (2R)-methyl-substituted derivative and then to (2R)-N-Boc-O-methyltyrosine or its nt-chloro derivative. Fusion of the A and B subunits was accomplished by initial esterification of the former with the latter, followed by macrocyclization using diphenyl phosphorazidate. In this way, cryptophycin-3, -4, and -29 were obtained along with the nonnatural cyclic depsipeptide 52. Epoxidation of cryptophycin-3 with dimethyldioxirane gave cryptophycin-1; analogous epoxidation of 52 afforded arenastatin A (cryptophycin-24).

  DOI：

  10.1021/jo9907585
• 作为产物：
  描述：

  (2S,2'R)-benzyl 2-[(3'-{[(tert-butoxy)carbonyl]amino}propionyl)oxy]-4-methylpentanoate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 benzyl (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionylamino]-propionyloxy]-4-methylpentanoate
  参考文献：
  名称：

  A concise synthesis of the cytotoxic depsipeptide arenastatin A

  摘要：

  Arenastatin A (1, cryptophycin 24) was synthesized by convergence of hydroxy eater 16 with amino acid derivative 27; two independent and highly efficient routes to 16 are disclosed. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)02014-0

文献信息

• Design and synthesis of a new class of cryptophycins based tubulin inhibitors
  作者：Arvind Kumar、Manjeet Kumar、Simmi Sharma、Santosh Kumar Guru、Shashi Bhushan、Bhahwal Ali Shah

  DOI：10.1016/j.ejmech.2014.11.068

  日期：2015.3

  Tubulin binding compounds represent one of the most attractive targets for anticancer drug development. They broadly fall into two categories viz., tubulin polymerization inhibitors, which block microtubule growth and destabilize microtubules like vinca alkaloids and cryptophycins, and the others, which polymerize microtubules into hyperstable forms represented by family of taxanes. In this context, we aimed at design and synthesis of cryptophycins based macrocyclic depsipeptides, which are synthetically more accessible, however have the basic information to target tubulins and establish structure activity relationship (SAR). Thus, a new class of cryptophycins based marocyclic depsipeptides with a truncated epoxide chain were synthesized as potential tubulin inhibitors. The resultant lead analogues 15a and 16a exhibited good anti-cancer activity, induced apoptosis, caused block/delay in cell cycle as well as significantly reduced the expression of alpha- and beta-tubulins. Molecular modelling studies show that 15a and 16a bind in the same domain as that of cryptophycins. (C) 2015 Elsevier Masson SAS. All rights reserved.