[(8R)-13,14,15-trimethoxy-5-methylsulfanyl-8-tricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,11,13-hexaenyl] benzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(8R)-13,14,15-trimethoxy-5-methylsulfanyl-8-tricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,11,13-hexaenyl] benzoate
• 化学式: C₂₆H₂₆O₅S
• 分子量: 450.555
• InChiKey: ZLWUTUQLJPJYQB-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  79.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  9,10,11-Trimethoxy-3-methylsulfanyl-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-ol 在 sodium hydroxide 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 [(8R)-13,14,15-trimethoxy-5-methylsulfanyl-8-tricyclo[9.4.0.02,7]pentadeca-1(15),2(7),3,5,11,13-hexaenyl] benzoate
  参考文献：
  名称：

  抗肿瘤药。第184部分。硫代秋水仙碱与胺反应衍生的化合物的合成和抗微管蛋白活性：内酰胺，醇和别硫代天冬氨酸类胡萝卜素的酯类似物† •

  摘要：

  合成了7- O-取代的脱氨基脱氧胆甾醇硫代甲基醚类似物，并评价了其对体外微管蛋白聚合的抑制作用。酮9是这项研究中的关键化合物，它是通过与苯胺反应而从噻吩酮6衍生而来的。化合物6与MeNH 2或BuNH 2的反应分别得到四环内酰胺7和8。旋光醇11a和11b是由外消旋体11通过化学拆分而获得的，包括分离出甲酸酯非对映异构体12a。和12b，然后进行碱性水解。通过X射线晶体学分析证实了12b的（a R，7 R）-构型。几乎所有外消旋和旋光的7- O-酰基或7- O-芳酰基化合物均对微管蛋白聚合反应具有强烈的抑制作用，IC 50值为1.7至5.1μM。一些试剂，例如内酰胺7和8，樟脑酸酯12a和12b，环己烷羧酸酯19a和19b，最值得注意的是（7 S）-苯甲酸酯15a，对聚合的影响可忽略不计，产生的IC 50值大于40μM。酮9表现出对微管蛋白聚合的强烈抑制作用，其程度可与硫代秋水仙烯（6）相

  DOI：

  10.1002/hlca.19980810516

文献信息

• Antitumor Agents. 183. Syntheses, Conformational Analyses, and Antitubulin Activity of Allothiocolchicinoids
  作者：Qian Shi、Ke Chen、Xin Chen、Arnold Brossi、Pascal Verdier-Pinard、Ernest Hamel、Andrew T. McPhail、Alexander Tropsha、Kuo-Hsiung Lee

  DOI：10.1021/jo980073p

  日期：1998.6.1

  7-O-Substituted analogues of allothiocochicine were synthesized and evaluated for their inhibitory effects on tubulin polymerization in vitro. Ketone 6, a key compound in this study, was derived from thiocolchicone 5 by ring contraction. The structure of 6 was determined from spectral data. Optically active alcohols 7a and 7b were obtained by reduction of ketone 6 followed by chemical resolution including a separation of the camphanate diastereomers 8a and 8b and basic hydrolysis. The aR,7R configuration of 8b was verified by X-ray crystallographic analysis. Almost all compounds had strong inhibitory effects on the tubulin polymerization reaction, with IC50 values from 1.7 to 9.0 mu M. The camphanates, cyclohexanates, and, most notably, the 7S-benzoate ester (10a), were inactive with IC50 values >40 mu M. Compounds 6 and 7a also showed potent antitumor activity with GI(50) values at nM concentration range for most cell lines in NCI's in vitro screening. Generally, the 7S enantiomers of colchicinoids with a troplone C-ring showed greater activity than the 7R enantiomers. In the current allothiocolchicinoid (with a benzenoid C-ring) study, only small differences occurred between the two active enantiomers of each pair. The acyl esters with a 7S configuration were slightly more active than the 7R isomers. However, the aroyl ester with a 7S configuration was less active than the 7R isomer. NMR, optical rotation, and molecular modeling studies revealed two conformers in a solvent-dependent equilibrium for both 7S and 7R isomers. In polar solvents, the molecular chirality in esters with a 7-O-aroyl substituent was reversed from aS to aR or from aR to aS at an intensified rate.