(R)-methyl 2-(1-(tert-butoxycarbonylamino)-2-(tert-butylthio)ethyl)-5-methyloxazole-4-carboxylate | 912656-41-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-methyl 2-(1-(tert-butoxycarbonylamino)-2-(tert-butylthio)ethyl)-5-methyloxazole-4-carboxylate
• 英文别名: methyl 2-[(1R)-2-tert-butylsulfanyl-1-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-5-methyl-1,3-oxazole-4-carboxylate
• CAS: 912656-41-8
• 化学式: C₁₇H₂₈N₂O₅S
• 分子量: 372.486
• InChiKey: SBKNVJAROXLZCC-NSHDSACASA-N

物化性质

• 熔点：
  104-106 °C
• 沸点：
  465.2±45.0 °C(Predicted)
• 密度：
  1.135±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2-(1-(tert-butoxycarbonylamino)-2-(tert-butylthio)ethyl)-5-methyloxazole-4-carboxylate 在 4-二甲氨基吡啶 盐酸 、 lithium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 伯吉斯试剂 、 4 A molecular sieve 、 叠氮磷酸二苯酯 、 1-羟基苯并三唑 、 甲基磺酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 98.0h， 生成 (12Z,22Z,32Z,72Z,82Z,92Z,12R)-6-(bromomethyl)-12-((tert-butylthio)methyl)-6-methoxy-15,25-dimethyl-5,11-diaza-1(2,4),2,3,7,8,9(4,2)-hexaoxazolacyclododecaphane-4,10-dione
  参考文献：
  名称：

  Total Synthesis of (R)-Telomestatin

  摘要：

  We have achieved a total synthesis of telomestatin, and its absolute configuration was determined to be (R). Coupling of cysteine-containing trisoxazole amine and serine-containing trisoxazole carboxylic acid, followed by macrocyclization, provided a 24-membered diamide. The seventh oxazole ring was formed by a Shin's procedure via dehydroamide. Cyclodehydration of a modified (R)-cysteine-(S-Bu-t) moiety using Kelly's method (PPh3(O)-Tf2O) with anisole furnished (R)-telomestatin, whose CD spectrum was in good agreement with that of the natural product.

  DOI：

  10.1021/ol061793i
• 作为产物：
  描述：

  N-叔丁氧羰基-S-叔丁基-L-半胱氨酸 在 pyridine-SO3 complex 、 碘 、 1-羟基苯并三唑 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (R)-methyl 2-(1-(tert-butoxycarbonylamino)-2-(tert-butylthio)ethyl)-5-methyloxazole-4-carboxylate
  参考文献：
  名称：

  Total Synthesis of (R)-Telomestatin

  摘要：

  We have achieved a total synthesis of telomestatin, and its absolute configuration was determined to be (R). Coupling of cysteine-containing trisoxazole amine and serine-containing trisoxazole carboxylic acid, followed by macrocyclization, provided a 24-membered diamide. The seventh oxazole ring was formed by a Shin's procedure via dehydroamide. Cyclodehydration of a modified (R)-cysteine-(S-Bu-t) moiety using Kelly's method (PPh3(O)-Tf2O) with anisole furnished (R)-telomestatin, whose CD spectrum was in good agreement with that of the natural product.

  DOI：

  10.1021/ol061793i

文献信息

• Telomestatin: Formal Total Synthesis and Cation-Mediated Interaction of Its <i>seco</i>-Derivatives with G-Quadruplexes
  作者：Jörg Linder、Thomas P. Garner、Huw E. L. Williams、Mark S. Searle、Christopher J. Moody

  DOI：10.1021/ja109158k

  日期：2011.2.2

  developing new potential therapeutic agents for cancer. An efficient formal total synthesis of telomestatin is reported in which the key steps are the use of dirhodium(II)-catalyzed reactions of diazocarbonyl compounds to generate six oxazole rings, demonstrating the power of rhodium carbene methodology in organic chemical synthesis. CD spectroscopy establishes that seco-derivatives of telomestatin are potent

  结构独特的天然产物 telomestatin 在大环排列中包含七个恶唑环和一个含硫噻唑啉。该化合物是端粒酶的有效抑制剂，因此为开发新的潜在癌症治疗剂提供了结构框架。报道了一种有效的端美他汀全合成，其中关键步骤是使用二氮羰基化合物的二铑 (II) 催化反应生成六个恶唑环，证明了铑卡宾方法在有机化学合成中的作用。CD 光谱表明，端粒抑制素的二级衍生物是源自人类端粒重复序列的 G-四链体结构的有效稳定剂。质谱研究，经分子动力学模拟证实，
• Derivatization of a tris-oxazole using Pd-catalyzed coupling reactions of a 5-bromooxazole moiety
  作者：Kazuaki Shibata、Masahito Yoshida、Takayuki Doi、Takashi Takahashi

  DOI：10.1016/j.tetlet.2010.01.064

  日期：2010.3

  Modification at the C5 position of an oxazole ring contained in a 2,4-concatenated tris-oxazole by Pd-catalyzed coupling reactions was performed. Novel Pd-catalyzed amination and alkoxylation of a 5-bromooxazole derivative as well as Suzuki-Miyaura coupling and Migita-Stille coupling have been demonstrated. A wide variety of functional groups, including aryl, heteroaryl, primary and secondary amines, and phenol, were introduced in the 5-bromooxazole moiety in moderate to excellent yields using Pd(OAc)(2)/S-PHOS or Pd(OAc)(2)/X-PHOS as a catalyst. (C) 2010 Elsevier Ltd. All rights reserved.
• Total Synthesis of (<i>R</i>)-Telomestatin
  作者：Takayuki Doi、Masahito Yoshida、Kazuo Shin-ya、Takashi Takahashi

  DOI：10.1021/ol061793i

  日期：2006.8.1

  We have achieved a total synthesis of telomestatin, and its absolute configuration was determined to be (R). Coupling of cysteine-containing trisoxazole amine and serine-containing trisoxazole carboxylic acid, followed by macrocyclization, provided a 24-membered diamide. The seventh oxazole ring was formed by a Shin's procedure via dehydroamide. Cyclodehydration of a modified (R)-cysteine-(S-Bu-t) moiety using Kelly's method (PPh3(O)-Tf2O) with anisole furnished (R)-telomestatin, whose CD spectrum was in good agreement with that of the natural product.