[3-((2S,8S,11R)-8-Allyl-11,14-dibenzyl-3,6,9,12,15-pentaoxo-14-trifluoromethyl-1,4,7,10,13-pentaaza-cyclopentadec-2-yl)-propyl]-carbamic acid benzyl ester | 653587-61-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [3-((2S,8S,11R)-8-Allyl-11,14-dibenzyl-3,6,9,12,15-pentaoxo-14-trifluoromethyl-1,4,7,10,13-pentaaza-cyclopentadec-2-yl)-propyl]-carbamic acid benzyl ester
• CAS: 653587-61-2
• 化学式: C₃₉H₄₃F₃N₆O₇
• 分子量: 764.802
• InChiKey: YTTLZHBEEWGGPG-LYPUTQENSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.76
• 重原子数：
  55.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  183.83
• 氢给体数：
  6.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  [3-((2S,8S,11R)-8-Allyl-11,14-dibenzyl-3,6,9,12,15-pentaoxo-14-trifluoromethyl-1,4,7,10,13-pentaaza-cyclopentadec-2-yl)-propyl]-carbamic acid benzyl ester 在 potassium permanganate 、 硫酸 作用下， 以 丙酮 为溶剂， 生成 [(2S,5R,11S)-5,8-Dibenzyl-11-(3-benzyloxycarbonylamino-propyl)-3,6,9,12,15-pentaoxo-8-trifluoromethyl-1,4,7,10,13-pentaaza-cyclopentadec-2-yl]-acetic acid
  参考文献：
  名称：

  Incorporation of the Unusual C^α-Fluoroalkylamino Acids into Cyclopeptides:  Synthesis of Arginine−Glycine−Aspartate (RGD) Analogues and Study of Their Conformational and Biological Behavior

  摘要：

  A series of six arginine-glycine-aspartate (RGD) cyclopeptide analogues containing a C-alpha-di- or trifluoromethylamino acid (alpha-Dfm or alpha-TfmAaa) at different positions of the ring were synthesized. All peptides were obtained in two diastereomeric forms, which were separated by HPLC. In vitro biological tests of the new cyclopeptides P were carried out in comparison with their corresponding cyclopeptides R lacking the alpha-fluoromethyl group. Five out of the six compounds P-I (containing (S)-alpha-Tfm-Aaa) showed activities in the nanomolar range, while the P-II compounds (containing (R)-a-Tfm-Aaa) were much less active or totally inactive. Only cyclo[RGDf-(S)-alpha TfmV] (P1-I) was found to be significantly more active than its model compound cyclo(RGDfV) (R1). The three-dimensional structure in water and DMSO was determined by NMR techniques and molecular dynamics (MD) calculations, but it was not possible to highlight significant differences in the backbone conformation of the peptides examined. Significant interproton distances, derived from nuclear Overhauser effect (NOE) experiments, were used to determine the absolute configuration of the side chains.

  DOI：

  10.1021/jm0511334
• 作为产物：
  描述：

  ((S)-2-{2-[(R)-2-((S)-2-Amino-pent-4-enoylamino)-3-phenyl-propionylamino]-2-benzyl-3,3,3-trifluoro-propionylamino}-5-benzyloxycarbonylamino-pentanoylamino)-acetic acid tert-butyl ester 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.25h， 生成 [3-((2S,8S,11R)-8-Allyl-11,14-dibenzyl-3,6,9,12,15-pentaoxo-14-trifluoromethyl-1,4,7,10,13-pentaaza-cyclopentadec-2-yl)-propyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  Incorporation of the Unusual C^α-Fluoroalkylamino Acids into Cyclopeptides:  Synthesis of Arginine−Glycine−Aspartate (RGD) Analogues and Study of Their Conformational and Biological Behavior

  摘要：

  A series of six arginine-glycine-aspartate (RGD) cyclopeptide analogues containing a C-alpha-di- or trifluoromethylamino acid (alpha-Dfm or alpha-TfmAaa) at different positions of the ring were synthesized. All peptides were obtained in two diastereomeric forms, which were separated by HPLC. In vitro biological tests of the new cyclopeptides P were carried out in comparison with their corresponding cyclopeptides R lacking the alpha-fluoromethyl group. Five out of the six compounds P-I (containing (S)-alpha-Tfm-Aaa) showed activities in the nanomolar range, while the P-II compounds (containing (R)-a-Tfm-Aaa) were much less active or totally inactive. Only cyclo[RGDf-(S)-alpha TfmV] (P1-I) was found to be significantly more active than its model compound cyclo(RGDfV) (R1). The three-dimensional structure in water and DMSO was determined by NMR techniques and molecular dynamics (MD) calculations, but it was not possible to highlight significant differences in the backbone conformation of the peptides examined. Significant interproton distances, derived from nuclear Overhauser effect (NOE) experiments, were used to determine the absolute configuration of the side chains.

  DOI：

  10.1021/jm0511334