Boc-D-Tyr(Me)-bAib(R)-OLeu-OH | 179093-49-3

• 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: Boc-D-Tyr(Me)-bAib(R)-OLeu-OH
• 英文别名: (2S)-2-[(2R)-3-[[(2R)-3-(4-methoxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-2-methylpropanoyl]oxy-4-methylpentanoic acid
• CAS: 179093-49-3
• 化学式: C₂₅H₃₈N₂O₈
• 分子量: 494.585
• InChiKey: IDXGZXHPBWBGBO-AHRSYUTCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  35
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Boc-D-Tyr(Me)-bAib(R)-OLeu-OH 在 4-二甲氨基吡啶 、 (苯并三唑-1-基氧基)二哌啶碳鎓六氟磷酸盐 、 trichlorobenzoyl chloride 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 反应 5.25h， 生成 (3S,6R,10S,16R) 3-isobutyl-10-(4-methoxybenzyl)-6-methyl-16-(3-phenylacryloyl)-1,4-dioxa-8,11-diazacyclohexadec-13(E)-ene-2,5,9,12-tetraone
  参考文献：
  名称：

  Total Synthesis of Cryptophycins and Their 16-(3-Phenylacryloyl) Derivatives

  摘要：

  Cryptophycin A, a cyclic depsipeptide isolated from the blue-green alga (cyanobacterium) Nostoc sp.GSV 224, has shown excellent activity against solid tumors implanted in mice. The benzylic epoxide, which was shown to be very important for biological, activity, is also fairly unstable under both acidic and alkaline conditions. The high doses needed to observe in vivo activity might be a result of this instability. In order to solve this problem while preserving the electrophilic character of the benzylic position, enones 1 and 2 have been proposed as promising analogs of the natural product, and a convergent total synthesis of these compounds is described. In addition, the same strategy was used to prepare Cryptophycins A, B, C, and D.

  DOI：

  10.1021/jo960816b
• 作为产物：
  描述：

  benzyl (2S)-2-[(2R)-3-[(2R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionylamino]-2-methylpropionyloxy]-4-methylpentanoate 在 palladium hydroxide - carbon 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 生成 Boc-D-Tyr(Me)-bAib(R)-OLeu-OH
  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

文献信息

• Synthesis and in vitro cytotoxicity of cryptophycins and related analogs
  作者：Jean-Marc de Muys、Rabindra Rej、Dieu Nguyen、Brian Go、Samuel Fortin、Jean-François Lavallée

  DOI：10.1016/0960-894x(96)00182-5

  日期：1996.5

  Several members of the Cryptophycin family were synthesised using a straightforward convergent approach, The proposed synthetic route was used to prepare novel analogs of Cryptophycins A and B in which the benzylic epoxide moiety was replaced by alternate electrophilic functions. The effect of these modifications on cytotoxic activity was determined on several tumor cell lines. (C) 1996 Elsevier Science Ltd