N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methylleucyl-N-methylvalyl tert-butyl ester | 103478-64-4

• 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
• 英文名称: N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methylleucyl-N-methylvalyl tert-butyl ester
• 英文别名: Fmoc-MeLeu-MeVal-O-t-Bu；Fmoc-N(Me)Leu-N(Me)Val-OtBu；tert-butyl (2S)-2-[[(2S)-2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]-4-methylpentanoyl]-methylamino]-3-methylbutanoate
• CAS: 103478-64-4
• 化学式: C₃₂H₄₄N₂O₅
• 分子量: 536.712
• InChiKey: IKXQUAWYEJVUTD-NSOVKSMOSA-N

物化性质

• 沸点：
  633.0±48.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methylleucyl-N-methylvalyl tert-butyl ester 在 双-乙基己氧苯酚甲氧苯基三嗪 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.67h， 生成 N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methylleucyl-N-methylleucyl-N-methylvalyl tert-butyl ester
  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：

  N-苄氧羰基-N-甲基-L-缬氨酸 在 palladium on activated charcoal 硫酸 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 叔丁醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 240.0h， 生成 N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methylleucyl-N-methylvalyl tert-butyl ester
  参考文献：
  名称：

  BOP-Cl mediated synthesis of the cyclosporine A 8-11 tetrapeptide fragment

  摘要：

  DOI：

  10.1021/jo00367a018

文献信息

• A novel thiazolium type peptide coupling reagent for hindered amino acids
  作者：Peng Li、Jie Cheng Xu

  DOI：10.1016/s0040-4039(99)01763-3

  日期：1999.11

  A highly efficient coupling reagent, 2-bromo-3-ethyl-4-methyl thiazolium tetrafluoroborate (BEMT), was designed, synthesized and successfully applied to the synthesis of oligopeptides containing N-alkyl or α-C-dialkyl amino acids. Its efficiency was evaluated by HPLC and 1H NMR methods, and demonstrated by synthesis of a number of N-methyl-rich peptide segments with good yields and negligible racemization

  设计，合成了高效偶联试剂2-溴-3-乙基-4-甲基噻唑四氟硼酸酯（BEMT），并将其成功地用于合成包含N-烷基或α- C-二烷基氨基酸的寡肽。通过HPLC和1 H NMR方法评价了其效率，并通过合成了许多具有良好产率和可忽略的外消旋作用的富含N-甲基的肽段。通过HPLC，1 H NMR和IR监测研究了偶联机理。有人提出不稳定的（酰氧基）噻唑盐和N-保护的氨基酸溴化物是主要的活性中间体，伴随着N的形成-乙基-4-甲基噻唑烷酮和少量的恶唑酮和N保护的氨基酸酸酐。