N-Methyl-(S)-leucyl-N-methyl-(S)-leucyl-N-methyl-(S)-valin-tert-butylester | 103478-69-9

• 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-Methyl-(S)-leucyl-N-methyl-(S)-leucyl-N-methyl-(S)-valin-tert-butylester
• 英文别名: (S)-MeLeu-(S)-MeLeu-(S)-MeVal-O-tert-Bu；H-MeLeu-MeLeu-MeVal-O^tBu；H-(Me)Leu-(Me)Leu-(Me)Val-O-(t-Bu)；MeLeu-MeLeu-MeVal-O-t-Bu；Me-Leu-N(Me)Leu-N(Me)Val-OtBu；tert-butyl (2S)-3-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2S)-4-methyl-2-(methylamino)pentanoyl]amino]pentanoyl]amino]butanoate
• CAS: 103478-69-9
• 化学式: C₂₄H₄₇N₃O₄
• 分子量: 441.655
• InChiKey: CQTMMFUEFRLZQO-UFYCRDLUSA-N

物化性质

• 沸点：
  524.3±45.0 °C(Predicted)
• 密度：
  0.985±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-Methyl-(S)-leucyl-N-methyl-(S)-leucyl-N-methyl-(S)-valin-tert-butylester 在 palladium on activated charcoal 氢气 、 potassium hydrogencarbonate 、 3,3'-Dicyano-4,4',6,6'-tetramethyl-2,2'-dipyridinyl-disulfid 、 三苯基膦 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 乙醇 、 氯仿 、 水 为溶剂， -20.0 ℃ 、294.18 kPa 条件下， 反应 29.0h， 生成 N-(Benzyloxycarbonyl)tetrapeptidsaeure
  参考文献：
  名称：

  Schmidt, Ulrich; Potzolli, Bernd, Liebigs Annalen der Chemie, 1987, p. 935 - 942

  摘要：

  DOI：
• 作为产物：
  描述：

  N-(Benzyloxycarbonyl)-N-methyl-(S)-valin-tert-butylester 在 palladium on activated charcoal 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 、 叔丁醇 为溶剂， 反应 48.0h， 生成 N-Methyl-(S)-leucyl-N-methyl-(S)-leucyl-N-methyl-(S)-valin-tert-butylester
  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

• Solution-Phase Synthesis of a Hindered <i>N</i>-Methylated Tetrapeptide Using Bts-Protected Amino Acid Chlorides:  Efficient Coupling and Methylation Steps Allow Purification by Extraction
  作者：Edwin Vedejs、Chutima Kongkittingam

  DOI：10.1021/jo9914115

  日期：2000.4.1

  N-Benzothiazole-2-sulfonyl (Bts)-protected amino acid chlorides were used to prepare the hindered cyclosporin 8-11 tetrapeptide subunit 1. The synthesis was performed via 3a and the deprotected amines 5a, 13, and 19, including three repeated cycles involving N-methylation using iodomethane/potassium carbonate, deprotection of the Bts group, and N-acylation with a N-Bts-amino acid chloride such as 9b

  使用N-苯并噻唑-2-磺酰基（Bts）保护的氨基酸氯化物制备受阻的环孢菌素8-11四肽亚基1。通过3a和脱保护的胺5a，13和19进行合成，包括三个重复循环包括使用碘甲烷/碳酸钾进行N-甲基化，Bts基团的脱保护以及用N-Bts-氨基酸氯化物（如9b或9c）进行N-酰化。在比较的三种Bts裂解方法（H3PO2 / THF； NaBH4 / EtOH； PhSH / K2CO3）中，第三种给出的总收率更高。用Bts保护的N-甲基氨基酸氯化物10b对5a进行N-酰化再脱保护也非常有效，并且可以用作11的替代途径。无需色谱法即可分离出每种脱保护的胺，无需使用简单的萃取方法即可去除中性物质。副产品。
• Solution synthesis of -methylated peptides by the diphenyl phosphinic mixed anhydride procedure.
  作者：I.J. Galpin、A.K. Mohammed、A. Patel

  DOI：10.1016/s0040-4020(01)86731-4

  日期：1988.1

  A proton n.m.r. method has been used to monitor racemisation during the coupling of -methylated amino acids by the diphenylphosphinic mixed anhydride procedure. No racemisation was observed when urethane protection was employed, but use of the benzoyl group led to extensive racemisation. The reagent was subsequently used for the assembly of several extensively -methylated peptides.

  在通过二苯基次膦混合酸酐法偶联-甲基化氨基酸的过程中，已经使用质子核磁共振法监测外消旋化。当采用氨基甲酸酯保护时未观察到外消旋化，但是使用苯甲酰基导致广泛的外消旋化。该试剂随后用于组装几种完全甲基化的肽。
• 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
  作者：Peng Li、Jie Cheng Xu

  DOI：10.1021/jo991687c

  日期：2000.5.1

  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.
• Synthesis of D-lysine8-cyclosporine A. Further characterization of BOP-Cl in the 2-7 hexapeptide fragment synthesis
  作者：William J. Colucci、Roger D. Tung、John A. Petri、Daniel H. Rich

  DOI：10.1021/jo00296a061

  日期：1990.4
• Synthesis of two linear octapeptide fragments of cyclosporin by Stepwise and frangment condensation stratigies
  作者：I.J. Galpin、A.K.A. Mohammed、A. Patel、G. Priestley

  DOI：10.1016/s0040-4020(01)86741-7

  日期：1988.1