(3S,4S)-4-hydroxy-3,5-dimethyl-6-(2-methylthiazol-4-yl)-1,5-hexadiene | 470462-89-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (3S,4S)-4-hydroxy-3,5-dimethyl-6-(2-methylthiazol-4-yl)-1,5-hexadiene
• 英文别名: (1E,3S,4S)-2,4-dimethyl-1-(2-methyl-1,3-thiazol-4-yl)hexa-1,5-dien-3-ol
• CAS: 470462-89-6
• 化学式: C₁₂H₁₇NOS
• 分子量: 223.339
• InChiKey: DCZNHNVLHSXIGL-YINUSBERSA-N

物化性质

• 沸点：
  360.2±30.0 °C(Predicted)
• 密度：
  1.089±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,4S)-4-hydroxy-3,5-dimethyl-6-(2-methylthiazol-4-yl)-1,5-hexadiene 在 吡啶 、 咪唑 、 2,6-二甲基吡啶 、 chromium dichloride 、 sodium chlorite 、 sodium dihydrogenphosphate 、 四氧化锇 、 氯化亚砜 、 邻苯二甲酸二甲酯 、 camphor-10-sulfonic acid 、 三乙基硼氢化锂 、 2,3-二甲基-1-丁烯 、 N-甲基吗啉氧化物 、 nickel dichloride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 、 正戊烷 为溶剂， 反应 72.5h， 生成
  参考文献：
  名称：

  Conformation−Activity Relationships in Polyketide Natural Products:  A New Perspective on the Rational Design of Epothilone Analogues

  摘要：

  The syntheses of C14-methyl analogues of epothilone B and D are described. Conformational analysis using computational methods, X-ray crystallography, and NMR studies showed that the stereochemistry at C14 has a pronounced effect on the conformation of the epoxide region. Biological assays indicated significant differences in their biological activity. Substitution which stabilized conformer I retained significant biological activity. In contrast, substitution which stabilized conformer II provided analogues with no measurable cytotoxicity. The conformation-activity relationships strongly support the importance of conformer I as the bioactive conformation of the epoxide region of epothilone. The approach presented here offers a new perspective on rational design of modified biologically active polyketides.

  DOI：

  10.1021/ja028196l
• 作为产物：
  描述：

  反-2-丁烯 、 (2E)-2-甲基-3-(2-甲基-1,3-噻唑-4-基)丙烯醛 在 正丁基锂 、 potassium tert-butylate 、 (-)-B-methoxydiisopinocampheylborane 、 三氟化硼乙醚 作用下， 以 四氢呋喃 、 正己烷 、 乙醚 为溶剂， 反应 8.5h， 以70%的产率得到(3S,4S)-4-hydroxy-3,5-dimethyl-6-(2-methylthiazol-4-yl)-1,5-hexadiene
  参考文献：
  名称：

  Conformation−Activity Relationships in Polyketide Natural Products:  A New Perspective on the Rational Design of Epothilone Analogues

  摘要：

  The syntheses of C14-methyl analogues of epothilone B and D are described. Conformational analysis using computational methods, X-ray crystallography, and NMR studies showed that the stereochemistry at C14 has a pronounced effect on the conformation of the epoxide region. Biological assays indicated significant differences in their biological activity. Substitution which stabilized conformer I retained significant biological activity. In contrast, substitution which stabilized conformer II provided analogues with no measurable cytotoxicity. The conformation-activity relationships strongly support the importance of conformer I as the bioactive conformation of the epoxide region of epothilone. The approach presented here offers a new perspective on rational design of modified biologically active polyketides.

  DOI：

  10.1021/ja028196l

文献信息

• Epothilone derivatives and methods for making and using the same
  申请人：——

  公开号：US20030045711A1

  公开（公告）日：2003-03-06

  This invention relates to compounds of formula (I) 1 and to pharmaceutically acceptable salts and solvates thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , W, X, Y, and Ar are as defined herein. Compounds of formula (I) are useful in the treatment of diseases or conditions characterized by cellular hyperproliferation. This invention also relates to means for the preparation of compounds of formula (I); formulations containing compounds of formula (I); and methods for the use of said compounds and formulations in the treatment of a disease or condition characterized by cellular hyperproliferation, including cancer.

  这项发明涉及公式（I）的化合物及其药用可接受的盐和溶剂化合物，其中R1、R2、R3、R4、R5、W、X、Y和Ar的定义如本文所述。公式（I）的化合物在治疗细胞过度增殖引起的疾病或症状方面是有用的。这项发明还涉及制备公式（I）化合物的方法；含有公式（I）化合物的配方；以及使用所述化合物和配方治疗细胞过度增殖引起的疾病或症状，包括癌症的方法。
• Conformation–activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone
  作者：Richard E. Taylor、Yue Chen、Gabriel M. Galvin、Praveen K. Pabba

  DOI：10.1039/b312213c

  日期：——

  The conformation–activity relationships for the biologically active polyketide, epothilone, have been determined. Computer-based molecular modeling and high field NMR techniques have provided the solution preferences for epothilones 1 and 2. For the C1–C8 polypropionate region, two conformational families, conformers 1 and 2, have been identified as having significant populations in polar and non-polar solvents. In the C11–C15 region, additional flexibility was observed and two local conformations have been identified as important, conformers 3 and 4. Epothilone analogues with altered conformational profiles have been designed and synthesized. Conformational analysis and the results of biological assays have been correlated to provide increased understanding of the biologically active conformation for the epothilone class of natural product. Conformation–activity relationships have been shown to be an important complement to structure–activity data.

  生物活性聚酮化合物埃坡霉素的构象与活性关系已经确定。基于计算机的分子建模和高场核磁共振技术为埃坡霉素 1 和 2 提供了解决方案的选择。对于 C1-C8 聚丙酸酯区域，两个构象家族，即构象异构体 1 和 2，已被确定为在极性和非极性区域具有显着的群体。 -极性溶剂。在 C11-C15 区域，观察到额外的灵活性，并且已确定两个重要的局部构象，即构象异构体 3 和 4。已设计并合成了具有改变构象特征的埃坡霉素类似物。构象分析和生物测定结果相互关联，以加深对埃坡霉素类天然产物的生物活性构象的了解。构象-活性关系已被证明是结构-活性数据的重要补充。
• Rapid access to epothilone analogs via semisynthetic degradation and reconstruction of epothilone D
  作者：Steven D. Dong、Kurt Sundermann、Karen M.J. Smith、Joseph Petryka、Fenghua Liu、David C. Myles

  DOI：10.1016/j.tetlet.2003.12.123

  日期：2004.2

  A facile and efficient route to epothilone analogs has been developed from the natural product epothilone D (1). Degradation of 1 via an oxidative cleavage sequence provides acid intermediate 4 rapidly in six steps. From 4, a variety of epothilone analogs have been prepared utilizing ring-closing metathesis to reconstruct the trisubstituted-12,13-double bond. Using this approach, we report a number of epothilone analogs with varying C-15 aromatic side chains and C-14 allylic substitutions and their biological activities. (C) 2004 Elsevier Ltd. All rights reserved.
• US6489314B1
  申请人：——

  公开号：US6489314B1

  公开（公告）日：2002-12-03
• US6589968B2
  申请人：——

  公开号：US6589968B2

  公开（公告）日：2003-07-08