N-[(9H-fluoren-9-ylmethoxy)carbonyl]-D-alanyl-N-methylleucyl-N-methylleucyl-N-methylvalyl-N-methylleucylnorvalylsarcosyl-N-methylleucyl-valyl-N-methylleucylalanine benzyl ester | 279219-99-7

• 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: N-[(9H-fluoren-9-ylmethoxy)carbonyl]-D-alanyl-N-methylleucyl-N-methylleucyl-N-methylvalyl-N-methylleucylnorvalylsarcosyl-N-methylleucyl-valyl-N-methylleucylalanine benzyl ester
• 英文别名: N-Fmoc-D-alanyl-N-methylleucyl-N-methylleucyl-N-methylvalyl-N-methylleucyl-norvalyl-sarcosyl-N-methylleucyl-valyl-N-methylleucyl-alanine benzyl ester；Fmoc-D-Ala-N(Me)Leu-N(Me)Leu-N(Me)Val-N(Me)Leu-Nva-Sar-N(Me)Leu-Val-N(Me)Leu-Ala-OBn；benzyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoyl]-methylamino]-4-methylpentanoyl]-methylamino]-4-methylpentanoyl]-methylamino]-3-methylbutanoyl]-methylamino]-4-methylpentanoyl]amino]pentanoyl]-methylamino]acetyl]-methylamino]-4-methylpentanoyl]amino]-3-methylbutanoyl]-methylamino]-4-methylpentanoyl]amino]propanoate
• CAS: 279219-99-7
• 化学式: C₈₂H₁₂₇N₁₁O₁₄
• 分子量: 1490.98
• InChiKey: LXZPWKTVDLNEHG-HKWBLFFXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.6
• 重原子数：
  107
• 可旋转键数：
  42
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  294
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N-[(9H-fluoren-9-ylmethoxy)carbonyl]-D-alanyl-N-methylleucyl-N-methylleucyl-N-methylvalyl-N-methylleucylnorvalylsarcosyl-N-methylleucyl-valyl-N-methylleucylalanine benzyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 H-D-Ala-(Me)Leu-(Me)Leu-(Me)Val-(Me)Leu-Nva-Sar-(Me)Leu-Val-(Me)Leu-Ala-OH
  参考文献：
  名称：

  Total Synthesis of Cyclosporin O Both in Solution and in the Solid Phase Using Novel Thiazolium-, Immonium-, and Pyridinium-Type Coupling Reagents:  BEMT, BDMP, and BEP¹

  摘要：

  Cyclosporin O (1), an extensively N-methylated immunosuppressive cyclic undecapeptide isolated from Tolypocladium inflatum Gams, was synthesized in 20-23% overall yield via 4 + 7 segment condensation and cyclization by the combined utilization of novel thiazolium- and immonium-type peptide coupling reagents 2-bromo-3-ethyl-4-methyl thiazolium tetrafluoroborate (BEMT) and 5-(1H-benzotriazol-1-yloxy)-3,4-dihydro-1-methyl 2H-pyrrolium hexachloroantimonate (BDMP) as well as compound 2-bromo-1-ethyl pyridinium tetrafluoroborate (BEP). BEMT and BEP, which have been proven to be very efficient for the coupling of peptide segments containing N-alkylated amino acid residues with respect to the fast reaction speed, low racemization, and high yields, were used to construct hindered amide bonds in CsO with the addition of HOAt, whereas the most efficient HOBt-derived immonium type reagent, BDMP, was used to perform the coupling of coded amino acids in CsO. Thus, the highly hindered protected 8-11 tetrapeptide 25 was successfully synthesized using BEMT in 65% yield, and the 1-7 heptapeptide 21 was obtained in 52-55% yield by the rationally combined utilization of BDMP, BEMT, and BEP. The synthesis of the linear undecapeptide 27 of CsO in the solid phase using BEMT and BEP was accomplished for the further evaluation of the effectiveness of these reagents.

  DOI：

  10.1021/jo991687c
• 作为产物：
  描述：

  Me-Leu-(Me)Leu-(Me)Val-(Me)Leu-Nva-Sar-(Me)Leu-Val-(Me)Leu-Ala-OBzl 、 9H-芴-9-基甲基 [(2R)-1-氯-1-氧代-2-丙基]氨基甲酸酯 在 锌 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以0.34 g的产率得到N-[(9H-fluoren-9-ylmethoxy)carbonyl]-D-alanyl-N-methylleucyl-N-methylleucyl-N-methylvalyl-N-methylleucylnorvalylsarcosyl-N-methylleucyl-valyl-N-methylleucylalanine benzyl ester
  参考文献：
  名称：

  锌粉介导的Fmoc-氨基酸氯化物的收敛法全合成环孢菌素O

  摘要：

  据报道，通过在溶液相中逐步组装氨基酸，可实现无差向异构和高效的免疫抑制剂环孢菌素O（CsO）的全合成。通过使用Fmoc-氨基酸氯化物进行偶联，并在中性条件下由锌粉介导。的空间耦合的产率和纯度受阻Ñ甲基氨基酸以Ñ甲基氨基酸在位置8，9，10，和11通过在这些特定接合点重复三次耦合增强。分离出与CsO和最终CsO有关的所有10种中间肽，并通过IR，1 H NMR，质谱和HPLC技术对其进行了完全表征。

  DOI：

  10.1021/jo701329w