(R)-14-methyl-epothilone D | 491611-04-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (R)-14-methyl-epothilone D
• 英文别名: (4S,7R,8S,9S,13Z,15R,16S)-4,8-dihydroxy-5,5,7,9,13,15-hexamethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione
• CAS: 491611-04-2
• 化学式: C₂₈H₄₃NO₅S
• 分子量: 505.719
• InChiKey: OUYNYIPEOCEALZ-HLFCKPNISA-N

物化性质

• 沸点：
  667.1±55.0 °C(Predicted)
• 密度：
  1.068±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-14-methyl-epothilone D 在 间氯过氧苯甲酸 作用下， 以55%的产率得到(1R,2S,3S,7S,10R,11S,12S,16S)-7,11-dihydroxy-2,8,8,10,12,16-hexamethyl-3-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
  参考文献：
  名称：

  Conformation–activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone

  摘要：

  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。

  DOI：

  10.1039/b312213c
• 作为产物：
  描述：

  (2E)-2-甲基-3-(2-甲基-1,3-噻唑-4-基)丙烯醛 在 吡啶 、 咪唑 、 2,6-二甲基吡啶 、 chromium dichloride 、 sodium chlorite 、 sodium dihydrogenphosphate 、 四氧化锇 、 正丁基锂 、 氯化亚砜 、 邻苯二甲酸二甲酯 、 2,4,6-三氯苯甲酰氯 、 camphor-10-sulfonic acid 、 potassium tert-butylate 、 四丁基氟化铵 、 三乙基硼氢化锂 、 2,3-二甲基-1-丁烯 、 N-甲基吗啉氧化物 、 N,N-二异丙基乙胺 、 三氟乙酸 、 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 94.0h， 生成 (R)-14-methyl-epothilone D
  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

• 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。
• Conformation−Activity Relationships in Polyketide Natural Products:  A New Perspective on the Rational Design of Epothilone Analogues
  作者：Richard E. Taylor、Yue Chen、Alicia Beatty、David C. Myles、Yiqing Zhou

  DOI：10.1021/ja028196l

  日期：2003.1.1

  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.