-L-valine methyl ester | 109745-89-3

• 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: -L-valine methyl ester
• 英文别名: N-valine methyl ester；Cbz-NMeVal-Val-OMe；Cbz-MeVal-Val-OMe；CbzNMeVal-ValOMe；Z-MeVal-Val-OMe；Cbz-N(Me)Val-Val-OMe；methyl (2S)-3-methyl-2-[[(2S)-3-methyl-2-[methyl(phenylmethoxycarbonyl)amino]butanoyl]amino]butanoate
• CAS: 109745-89-3
• 化学式: C₂₀H₃₀N₂O₅
• 分子量: 378.469
• InChiKey: MURWDXUCCGEKNT-IRXDYDNUSA-N

物化性质

• 沸点：
  508.6±43.0 °C(Predicted)
• 密度：
  1.106±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-苄氧羰基-N-甲基-L-缬氨酸 、 HBr*H--Val-OMe 在 N-羟基-7-氮杂苯并三氮唑 、 2-Chloro-1,3-dimethylimidazolidinium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以91%的产率得到-L-valine methyl ester
  参考文献：
  名称：

  Convergent Synthesis of Dolastatin 15 by Solid Phase Coupling of an N-Methylamino Acid

  摘要：

  Convergent synthesis of dolastatin 15 (1), a cytostatic depsipeptide isolated from the Indian Ocean sea hare, has been described. For construction of the backbone, a single-step condensation of peptide fragment 2 and pyrrolidone fragment 3 was successfully performed using 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate (CIP) developed by us as an efficient coupling reagent. Coupling of an N-methylamino acid on solid support was first achieved using CTP for the efficient synthesis of peptide fragment 2. The effectiveness of CIP for the coupling of N-methylamino acids in solution and on solid support were clarified by the syntheses of model di- and tripeptides.

  DOI：

  10.1021/jo981055a

文献信息

• Brop: A new reagent for coupling N-methylated amino acids
  作者：Jacques Coste、Marie-Noëlle Dufour、Antoine Pantaloni、Bertrand Castro

  DOI：10.1016/s0040-4039(00)94598-2

  日期：1990.1

  BroP (bromo tris(dimethylamino) phosphonium hexafluorophosphate) is a particularly suitable reagent for coupling N-methylated amino acids. It is stable and gives very high yields in short reaction times. Dipeptides are obtained without appreciable epimerization.

  BroP（溴化三（二甲基氨基）六氟磷酸phospho）是用于偶联N-甲基化氨基酸的特别合适的试剂。它是稳定的，并且在短的反应时间内给出了很高的产率。在没有明显差向异构的情况下获得二肽。
• 2-Mercaptopyridine-1-oxide-based peptide coupling reagents
  作者：Fernando Albericio、Miguel A Bailén、Rafael Chinchilla、David J Dodsworth、Carmen Nájera

  DOI：10.1016/s0040-4020(01)00985-1

  日期：2001.11

  3-tetramethylurea (TMU) or 1,3-dimethylpropyleneurea (DMPU), have been employed as reagents in solution and solid-phase peptide coupling chemistry. Furthermore, 2-mercaptopyridine-1-oxide has been employed as racemization-reducing additive combined with the new thiouronium salts and other frequently used peptide coupling reagents such as DCC or TBTU.

  硫脲盐S-（1-氧化-2-吡啶基）-1,1,3,3-四甲基硫脲六氟磷酸盐（HOTT）和四氟硼酸盐（TOTT），以及S-（1-氧化-2-吡啶基）-1,3 -由2-巯基吡啶-1-氧化物和1,1,3,3-四甲基脲（TMU）或1,3-二甲基丙烯脲（DMPU）制得的-二甲基-1,3-三亚甲基硫脲六氟磷酸盐（HODT）和四氟硼酸盐（TODT），已被用作溶液和固相肽偶联化学中的试剂。此外，2-巯基吡啶-1-氧化物已被用作减少外消旋的添加剂，并与新的硫脲盐和其他常用的肽偶联剂如DCC或TBTU结合使用。
• Oxybenzotriazole free peptide coupling reagents for N-methylated amino acids
  作者：Jacques Coste、Eric Frérot、Patrick Jouin、Bertrand Castro

  DOI：10.1016/0040-4039(91)85015-w

  日期：1991.4

  The main product of N-methylated amino acid coupling, when oxybenzotriazole is present in the reagent (BOP, PyBOP, HBPyU) or as an additive (DCC/HOBt), is the weakly reactive benzotriazolyl ester. On the other hand, the corresponding new halogenated reagents PyBroP, PyCloP and PyClU give very good results and can be recommended.

  当试剂（BOP，PyBOP，HBPyU）中存在氧苯并三唑或作为添加剂（DCC / HOBt）存在时，N-甲基化氨基酸偶联的主要产物是弱反应性苯并三唑基酯。另一方面，相应的新型卤化试剂PyBroP，PyCloP和PyClU效果非常好，值得推荐。
• 10.1002/recl.19941130904
  作者：Wijkmans, Jac C. H. M.、Kruijtzer, John A. W.、Marel, Gijs A. van der、Boom, Jacques H. van、Bloemhoff, Wim

  DOI：10.1002/recl.19941130904

  日期：——
• Coupling N-Methylated Amino Acids Using PyBroP and PyCloP Halogenophosphonium Salts: Mechanism and Fields of Application
  作者：Jacques Coste、Eric Frerot、Patrick Jouin

  DOI：10.1021/jo00088a027

  日期：1994.5

  PyBroP (1) and PyCloP (2), two halotripyrrolidinophosphonium hexafluorophosphates, are peptide-coupling reagents highly efficient for coupling N-methylated amino esters, in contrast with PyBOP (3), the hydroxybenzotriazolyl analogue. These halogenophosphonium salts 1 and 2 are convenient (one-pot reactions) stable solids soluble in conventional solvents. Use of them gave an excellent peptide yield with essentially no epimerization. Activation with these reagents probably involves the formation of an (acyloxy)phosphonium, as shown in the case of 2,4,6-trimethylbenzoic acid activation. In the case of reagents 1 and 2, oxazolone and/or a symmetrical anhydride were intermediates which were rapidly aminolyzed. In contrast, the benzotriazolyl ester intermediate which was formed with PyBOP (3) was poorly reactive with N-methylated amino esters. PyBroP (1) and PyCloP (2) were less efficient in the coupling of some Boc-amino acids because of N-carboxyanhydride formation; this was particularly the case when Boc-Val-OH or Boc-MeVal-OH was coupled with MeVal-OMe.