(12S,27R)-27-(tert-butylsulfanylmethyl)-12-(hydroxymethyl)-4,30-dimethyl-3,7,14,18,22,29-hexaoxa-11,26,31,32,33,34,35,36-octazaheptacyclo[26.2.1.12,5.16,9.113,16.117,20.121,24]hexatriaconta-1(30),2(36),4,6(35),8,13(34),15,17(33),19,21(32),23,28(31)-dodecaene-10,25-dione | 912656-57-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (12S,27R)-27-(tert-butylsulfanylmethyl)-12-(hydroxymethyl)-4,30-dimethyl-3,7,14,18,22,29-hexaoxa-11,26,31,32,33,34,35,36-octazaheptacyclo[26.2.1.12,5.16,9.113,16.117,20.121,24]hexatriaconta-1(30),2(36),4,6(35),8,13(34),15,17(33),19,21(32),23,28(31)-dodecaene-10,25-dione
• CAS: 912656-57-6
• 化学式: C₃₀H₂₈N₈O₉S
• 分子量: 676.667
• InChiKey: CCCWQGIQIUKPHU-LIRRHRJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  48
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  260
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  (12S,27R)-27-(tert-butylsulfanylmethyl)-12-(hydroxymethyl)-4,30-dimethyl-3,7,14,18,22,29-hexaoxa-11,26,31,32,33,34,35,36-octazaheptacyclo[26.2.1.12,5.16,9.113,16.117,20.121,24]hexatriaconta-1(30),2(36),4,6(35),8,13(34),15,17(33),19,21(32),23,28(31)-dodecaene-10,25-dione 在 N-溴代丁二酰亚胺(NBS) 、 4 A molecular sieve 、 甲基磺酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 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 4-二甲氨基吡啶 盐酸 、 lithium hydroxide 、 伯吉斯试剂 、 pyridine-SO3 complex 、 叠氮磷酸二苯酯 、 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 、 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 96.0h， 生成 (12S,27R)-27-(tert-butylsulfanylmethyl)-12-(hydroxymethyl)-4,30-dimethyl-3,7,14,18,22,29-hexaoxa-11,26,31,32,33,34,35,36-octazaheptacyclo[26.2.1.12,5.16,9.113,16.117,20.121,24]hexatriaconta-1(30),2(36),4,6(35),8,13(34),15,17(33),19,21(32),23,28(31)-dodecaene-10,25-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

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，
• (S)-Stereoisomer of telomestatin as a potent G-quadruplex binder and telomerase inhibitor
  作者：Takayuki Doi、Kazuaki Shibata、Masahito Yoshida、Motoki Takagi、Masayuki Tera、Kazuo Nagasawa、Kazuo Shin-ya、Takashi Takahashi

  DOI：10.1039/c0ob00513d

  日期：——

  Total synthesis of the (S)-stereoisomer of telomestatin (1) was accomplished. (S)-Telomestatin exhibited potency four times that of the natural product, (R)-telomestatin, which was the most potent telomerase inhibitor previously reported. In the circular dichroism spectral analysis of the complexes possessing randomly structured single-stranded d[TTAGGG]4 oligonucleotide, (S)-telomestatin, like (R)-telomestatin, induced an antiparallel G-quadruplex structure. The melting temperature (Tm) value of the (S)-isomer complex was greater than that of the (R)-telomestatin complex. Therefore, it is concluded that the stereochemistry of the thiazoline of telomestatin is important to the binding ability of a G-quadruplex binder, and (S)-telomestatin as a G-quadruplex binder is more potent than the natural product.

  (S)-泰洛美司汀（1）的立体异构体的全合成已经完成。(S)-泰洛美司汀的效力是天然产物(R)-泰洛美司汀的四倍，后者是此前报道的最有效的端粒酶抑制剂。在具有随机结构单链d[TTAGGG]4寡核苷酸的复合物的圆二色光谱分析中，(S)-泰洛美司汀与(R)-泰洛美司汀一样，诱导了反平行G-四联体结构。(S)-异构体复合物的熔化温度（Tm）值大于(R)-泰洛美司汀复合物的熔化温度（Tm）值。因此，可以得出结论，泰洛美司汀噻唑啉的立体化学对于G-四联体结合剂的结合能力非常重要，并且(S)-泰洛美司汀作为G-四联体结合剂比天然产物更有效。
• 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.