dolastatin 16 | 192214-57-6

• 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: dolastatin 16
• 英文别名: cyclo[OAla-Pro-D-OVal-D-N(Me)Val-Pro-hPhe(bR-Me)-Pro-bAla(2R-Me,3R-iPr)]；(3S,6S,12R,15R,18S,24S,27R,28R,31S)-13,24,27-trimethyl-3-[(2R)-1-phenylpropan-2-yl]-12,15,28-tri(propan-2-yl)-16,25-dioxa-1,4,10,13,22,29-hexazatetracyclo[29.3.0.06,10.018,22]tetratriacontane-2,5,11,14,17,23,26,30-octone
• CAS: 192214-57-6
• 化学式: C₄₇H₇₀N₆O₁₀
• 分子量: 879.107
• InChiKey: JXOFEBNJOOEXJY-QNCIAAGJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  63
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  192
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  dolastatin 16 在 N-甲基吗啉 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺-d7 为溶剂， 反应 6.0h， 生成 methyl (2S)-2-[[(2R,3R)-3-[[(2S)-1-[(2S,3R)-2-[[(2S)-1-[(2R)-2-[[(2R)-2-hydroxy-3-methylbutanoyl]-methylamino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-methyl-4-phenylbutanoyl]pyrrolidine-2-carbonyl]amino]-2,4-dimethylpentanoyl]amino]-2-phenylacetate
  参考文献：
  名称：

  Veraguamides A−G, Cyclic Hexadepsipeptides from a Dolastatin 16-Producing Cyanobacterium Symploca cf. hydnoides from Guam

  摘要：

  Cytotoxicity-directed purification of a Symploca cf. hydnoides sample from Cetti Bay, Guam, afforded seven new cyclic depsipeptides, veraguamides A-G (1-7), together with the known compound dolastatin 16. The planar structures of 1-7 were elucidated using NMR and MS experiments, while enantioselective HPLC and Mosher's analysis of acid and base hydrolysates, respectively, were utilized to assign the absolute configurations of the stereocenters. Veraguamides A-G (1-7) are characterized by the presence of an invariant proline residue, multiple N-methylated amino acids, an alpha-hydroxy acid, and a C(8)-polyketide-derived beta-hydroxy acid moiety with a characteristic terminus as either an alkynyl bromide, alkyne, or vinyl group. These compounds and a semisynthetic analogue (8) showed moderate to weak cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Preliminary structure-activity relationship analysis identified several sensitive positions in the veraguamide scaffold that affect the cytotoxic activity of this compound class. Dolastatin 16 showed only weak cytotoxic activity on both cell lines tested. The complete stereostructure of dolastatin 16 was proposed for the first time through degradation followed by a combination of advanced Marfey's analysis and modified Mosher's analysis using phenylglycine methyl ester as a chiral anisotropic reagent.

  DOI：

  10.1021/np200076t

文献信息

• Veraguamides A−G, Cyclic Hexadepsipeptides from a Dolastatin 16-Producing Cyanobacterium <i>Symploca</i> cf. <i>hydnoides</i> from Guam
  作者：Lilibeth A. Salvador、Jason S. Biggs、Valerie J. Paul、Hendrik Luesch

  DOI：10.1021/np200076t

  日期：2011.5.27

  Cytotoxicity-directed purification of a Symploca cf. hydnoides sample from Cetti Bay, Guam, afforded seven new cyclic depsipeptides, veraguamides A-G (1-7), together with the known compound dolastatin 16. The planar structures of 1-7 were elucidated using NMR and MS experiments, while enantioselective HPLC and Mosher's analysis of acid and base hydrolysates, respectively, were utilized to assign the absolute configurations of the stereocenters. Veraguamides A-G (1-7) are characterized by the presence of an invariant proline residue, multiple N-methylated amino acids, an alpha-hydroxy acid, and a C(8)-polyketide-derived beta-hydroxy acid moiety with a characteristic terminus as either an alkynyl bromide, alkyne, or vinyl group. These compounds and a semisynthetic analogue (8) showed moderate to weak cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Preliminary structure-activity relationship analysis identified several sensitive positions in the veraguamide scaffold that affect the cytotoxic activity of this compound class. Dolastatin 16 showed only weak cytotoxic activity on both cell lines tested. The complete stereostructure of dolastatin 16 was proposed for the first time through degradation followed by a combination of advanced Marfey's analysis and modified Mosher's analysis using phenylglycine methyl ester as a chiral anisotropic reagent.