grassypeptolide C | 1256936-18-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: grassypeptolide C
• 英文别名: (2R,5R,9S,12S,18S,21S,24R,25R,28R,31R,34R)-9,21-dibenzyl-2-ethyl-28-[(1R)-1-hydroxyethyl]-10,19,24,25,32-pentamethyl-31-(2-methylpropyl)-18-propan-2-yl-22-oxa-7,36-dithia-3,10,16,19,26,29,32,37,38-nonazatetracyclo[32.2.1.15,8.012,16]octatriaconta-1(37),8(38)-diene-4,11,17,20,23,27,30,33-octone
• CAS: 1256936-18-1
• 化学式: C₅₆H₇₉N₉O₁₀S₂
• 分子量: 1102.43
• InChiKey: KUUZFDUZAFJFSJ-WLXMMAAGSA-N

物化性质

• 沸点：
  1266.6±65.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  77
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  290
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  grassypeptolide C 在 ruthenium trichloride 、 sodium periodate 、 盐酸 作用下， 以 四氯化碳 、 水 、 乙腈 为溶剂， 反应 17.0h， 生成 N-甲基-L-苯丙氨酸 、 N-甲基-D-苯丙氨酸
  参考文献：
  名称：

  Grassypeptolides A−C, Cytotoxic Bis-thiazoline Containing Marine Cyclodepsipeptides

  摘要：

  Grassypeptolides A-C (1-3), a group of closely related bis-thiazoline containing cyclic depsipeptides, have been isolated from extracts of the marine cyanobacterium Lyngbya confervoides. Although structural differences between the analogues are minimal, comparison of the in vitro cytotoxicity of the series revealed a structure-activity relationship. When the ethyl substituent of 1 is changed to a methyl substituent in 2, activity is only slightly reduced (3-4-fold), whereas inversion of the Phe unit flanking the bis-thiazoline moiety results in 16-23-fold greater potency. We show that both 1 and 3 cause G1 phase cell cycle arrest at lower concentrations, followed at higher concentrations by G2/M phase arrest, and that these compounds bind Cu2+. and Zn2+. The three-dimensional structure of 2 was determined by MS, NMR, and X-ray crystallography, and the structure of 3 was established by MS, NMR, and chemical degradation. The structure of 3 was explored by in silico molecular modeling, revealing subtle differences in overall conformation between 1 and 3. Attempts to interconvert 1 and 3 with base were unsuccessful, but enzymatic conversion may be possible and could be a novel form of activation for chemical defense.

  DOI：

  10.1021/jo1013564

文献信息

• Grassypeptolides A−C, Cytotoxic Bis-thiazoline Containing Marine Cyclodepsipeptides
  作者：Jason C. Kwan、Ranjala Ratnayake、Khalil A. Abboud、Valerie J. Paul、Hendrik Luesch

  DOI：10.1021/jo1013564

  日期：2010.12.3

  Grassypeptolides A-C (1-3), a group of closely related bis-thiazoline containing cyclic depsipeptides, have been isolated from extracts of the marine cyanobacterium Lyngbya confervoides. Although structural differences between the analogues are minimal, comparison of the in vitro cytotoxicity of the series revealed a structure-activity relationship. When the ethyl substituent of 1 is changed to a methyl substituent in 2, activity is only slightly reduced (3-4-fold), whereas inversion of the Phe unit flanking the bis-thiazoline moiety results in 16-23-fold greater potency. We show that both 1 and 3 cause G1 phase cell cycle arrest at lower concentrations, followed at higher concentrations by G2/M phase arrest, and that these compounds bind Cu2+. and Zn2+. The three-dimensional structure of 2 was determined by MS, NMR, and X-ray crystallography, and the structure of 3 was established by MS, NMR, and chemical degradation. The structure of 3 was explored by in silico molecular modeling, revealing subtle differences in overall conformation between 1 and 3. Attempts to interconvert 1 and 3 with base were unsuccessful, but enzymatic conversion may be possible and could be a novel form of activation for chemical defense.