| 115160-84-4

• 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
• CAS: 115160-84-4
• 化学式: C₈₆H₁₃₁N₁₁O₁₅
• 分子量: 1559.05
• InChiKey: WUWDQLRJLXZEAZ-SUSBSRTRSA-N

物化性质

• 沸点：
  1407.4±65.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.95
• 重原子数：
  112.0
• 可旋转键数：
  40.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  314.33
• 氢给体数：
  5.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  在 4-二甲氨基吡啶 、 sodium hydroxide 、 (PrPO₂)3 作用下， 生成 29-Ethyl-26-[(4E)-1-hydroxy-2-methyl-4-hexen-1-yl]-2,8,17,20-tetraisobutyl-5,23-diisopropyl-7,11,14,16,19,22,25,31-octamethyl-1,4,7,10,13,16,19,22,25,28,31-undecaazabicyclo[30.3.1]hexatriacontane-3,6, 9,12,15,18,21,24,27,30,36-undecone
  参考文献：
  名称：

  Synthesis, conformation and immunosuppressive activity of a conformationally restricted cyclosporin lactam analog

  摘要：

  Cyclosporine A (CsA, 1), an immunosuppressive cyclic undecapeptide, in apolar solvents adopts a II' beta-turn at the Sar3-MeLeu4 residues. [D-Proline3]Cs has been reported to be a nonimmunosuppressive analogue in which the II' beta-turn is retained. In order to determine if this loss of activity is caused by steric hindrance between the Cs analogue and its receptor or is caused by a change in the peptide conformation, an analogue that stabilizes a II' beta-turn has been synthesized, [lactam3,4]Cs. We also have studied the solution conformation of two other analogues, [D-MeAla3]Cs and [L-MeAla3]Cs. The conformations have been established by 1D difference NOE and 2D (NOESY or ROESY) NMR. The conformations of [lactam3,4]Cs and [D-MeAla3]Cs are indistinguishable from that of CsA in solution. [L-MeAla3]Cs was found to adopt a conformation with a cis amide bond between Sar3 and MeLeu4. The inhibition of concanavalin A stimulated thymocytes by CsA, [D-MeAla3]Cs, [L-MeAla3]Cs, and [lactam3,4]Cs gave IC50 values (nM) of 5, 6, 100, and 100, respectively. The weak immunosuppressive activity of [lactam3,4]Cs possessing the II' beta-turn suggests that the loss of activity for 4 is due to steric hindrance with the Cs receptor.

  DOI：

  10.1021/jm00117a022
• 作为产物：
  描述：

  Fmoc-D-Ala-MeLeu-MeLeu-MeVal-OH 、 <(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylaino)-6-octenoyl>-L-2-aminobutyryl-(2S)-<(3S)-3-(N-methylamino)-2-oxo-1-piperidinyl>-4-methyl-2-pentanyl-L-valyl-N-methyl-L-leucyl-L-alanine benzyl ester 在 N-甲基吗啉 、 双(2-氧代-3-恶唑烷基)次磷酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 以64%的产率得到
  参考文献：
  名称：

  Synthesis, conformation and immunosuppressive activity of a conformationally restricted cyclosporin lactam analog

  摘要：

  Cyclosporine A (CsA, 1), an immunosuppressive cyclic undecapeptide, in apolar solvents adopts a II' beta-turn at the Sar3-MeLeu4 residues. [D-Proline3]Cs has been reported to be a nonimmunosuppressive analogue in which the II' beta-turn is retained. In order to determine if this loss of activity is caused by steric hindrance between the Cs analogue and its receptor or is caused by a change in the peptide conformation, an analogue that stabilizes a II' beta-turn has been synthesized, [lactam3,4]Cs. We also have studied the solution conformation of two other analogues, [D-MeAla3]Cs and [L-MeAla3]Cs. The conformations have been established by 1D difference NOE and 2D (NOESY or ROESY) NMR. The conformations of [lactam3,4]Cs and [D-MeAla3]Cs are indistinguishable from that of CsA in solution. [L-MeAla3]Cs was found to adopt a conformation with a cis amide bond between Sar3 and MeLeu4. The inhibition of concanavalin A stimulated thymocytes by CsA, [D-MeAla3]Cs, [L-MeAla3]Cs, and [lactam3,4]Cs gave IC50 values (nM) of 5, 6, 100, and 100, respectively. The weak immunosuppressive activity of [lactam3,4]Cs possessing the II' beta-turn suggests that the loss of activity for 4 is due to steric hindrance with the Cs receptor.

  DOI：

  10.1021/jm00117a022