(12S,27S)-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 | 1236066-33-3

• 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,27S)-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: 1236066-33-3
• 化学式: C₃₀H₂₈N₈O₉S
• 分子量: 676.667
• InChiKey: CCCWQGIQIUKPHU-IFXJQAMLSA-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

• 作为产物：
  描述：

  2-[2-[2-[(1R)-1-[[2-[2-[2-[(1S)-1-amino-2-hydroxyethyl]-1,3-oxazol-4-yl]-1,3-oxazol-4-yl]-1,3-oxazole-4-carbonyl]amino]-2-tert-butylsulfanylethyl]-5-methyl-1,3-oxazol-4-yl]-5-methyl-1,3-oxazol-4-yl]-1,3-oxazole-4-carboxylic acid 在 4-二甲氨基吡啶 、 叠氮磷酸二苯酯 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 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 、 (12S,27S)-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：

  (S)-Stereoisomer of telomestatin as a potent G-quadruplex binder and telomerase inhibitor

  摘要：

  (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。

  DOI：

  10.1039/c0ob00513d

文献信息

• (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。