-N-methyl-L-valine methyl ester | 88790-10-7

• 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-methyl-L-valine methyl ester
• 英文别名: N-(tert-butyloxycarbonyl)-valyl-methylvaline methyl ester；Boc-Val-N-Me-Val-OMe；Boc-Val-MeVal-OMe；N-Boc-L-Val-N-Me-L-Val-OMe；Boc-Val-N(Me)Val-OMe；methyl (2S)-3-methyl-2-[methyl-[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]butanoate
• CAS: 88790-10-7
• 化学式: C₁₇H₃₂N₂O₅
• 分子量: 344.451
• InChiKey: BGRFXZWAIKCQQO-STQMWFEESA-N

物化性质

• 沸点：
  444.5±30.0 °C(Predicted)
• 密度：
  1.041±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  -N-methyl-L-valine methyl ester 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 2-bromo-1-ethylpyridin-1-ium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 (S)-1-[(S)-1-((S)-2-{[(S)-2-((S)-2-Dimethylamino-3-methyl-butyrylamino)-3-methyl-butyryl]-methyl-amino}-3-methyl-butyryl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carboxylic acid benzyl ester
  参考文献：
  名称：

  1-乙基2-卤吡啶鎓盐，溶液和固相中高效阻碍肽合成的高效偶联试剂

  摘要：

  1-乙基-2-卤代吡啶鎓盐，BEP，FEP，BEPH和FEPH，合成并证明是含有受阻的肽的合成是非常有效的Ñ甲基化的或Ç α，Ç α-二烷基化的氨基酸残基。HPLC对模型反应的监测表明，与通常使用的卤化铀盐和phospho盐相比，这些吡啶鎓盐具有更高的反应活性和更低的消旋性。通过合成一系列受阻的寡肽和活性酯，具有良好的收率和方便的后处理，进一步证明了这些吡啶鎓类偶联剂的效率。使用这些吡啶鎓盐还成功合成了环孢菌素A（CsA）的8-11四肽片段和Dolastatin 15的五肽部分。这些吡啶鎓类偶联剂对SPPS的效率还通过CsA的极受阻碍的8-11肽段和CsO的线性十一肽的固相合成证明。1 H NMR，IR和HPLC。提出主要的反应性中间体是N-保护的氨基酸或肽的相应的酰卤和酰氧基吡啶鎓盐。

  DOI：

  10.1016/s0040-4020(00)00657-8
• 作为产物：
  描述：

  N-苄氧羰基-N-甲基-L-缬氨酸 在 palladium on activated charcoal 盐酸 、 氢气 、 N,N-二异丙基乙胺 、 chlorotri(pyrrolidin-1-yl)phosphonium hexafluorophosphate 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 7.02h， 生成 -N-methyl-L-valine methyl ester
  参考文献：
  名称：

  Coupling N-Methylated Amino Acids Using PyBroP and PyCloP Halogenophosphonium Salts: Mechanism and Fields of Application

  摘要：

  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.

  DOI：

  10.1021/jo00088a027
• 作为试剂：
  描述：

  二碘甲烷 、 3,4-二氢-1-苯基萘 在 diethylzinc 、 -N-methyl-L-valine methyl ester 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以69%的产率得到7b-Phenyl-1,1a,2,3-tetrahydrocyclopropa[a]naphthalene
  参考文献：
  名称：

  [EN] ASYMMETRIC CYCLOPROPANATION
  [FR] CYCLOPROPANATION ASYMETRIQUE

  摘要：

  公开号：

  WO2005033050A3

文献信息

• CF3-NO2-PyBOP1: A new and highly efficient coupling reagent for N-methyl amino acids
  作者：J.C.H.M Wijkmans、F.A.A Blok、G.A van der Marel、J.H van Boom、W Bloemhoff

  DOI：10.1016/0040-4039(95)00807-o

  日期：1995.6

  1-Hydroxy-4-nitro-6-(trifluoromethyl)benzotriazole-containing phosphonium salt CF3-NO2PyBOP (1h) proved to be a powerful reagent for in situ coupling of N-methylated amino acids.

  含1-羟基-4-硝基-6-（三氟甲基）苯并三唑的phospho盐CF 3 -NO 2 PyBOP（1h）被证明是用于原位偶联N-甲基化氨基酸的有效试剂。
• A Flexible Asymmetric Approach to Methyl 5-Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A
  作者：Hong-Qiao Lan、Jian-Liang Ye、Ai-E Wang、Yuan-Ping Ruan、Pei-Qiang Huang

  DOI：10.1002/chem.201002063

  日期：2011.1.17

  By using a methyl tetramate derivative (R)‐ or (S)‐9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)‐ or (S)‐5‐alkyltetramates (2) is disclosed. Among the synthesized methyl 5‐alkyltetramates 2, methyl 5‐methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5‐benzyltetramate (2 g) is a substructure

  通过使用四甲基甲酸酯衍生物（R）‐或（S）‐9作为新型手性结构单元，可以直接，灵活且高度对映选择性地合成四甲基（R）‐或（S）‐5‐烷基四酸酯（2）。披露。在合成的5-烷基四酸甲酯2中，在细胞毒性的mirabimide E（4）和dysideapyrrolidone（5）中发现了5-甲基四酸甲酯（2 a），而5-苄基四酸甲酯（2 g）是有效的抗肿瘤药物dolastatin 15中的子结构。 （3）。在此方法的基础上，从（S）-9的七个步骤完成了抗有丝分裂四肽belamide A（7）的首次不对称合成，总收率为23.8％。不仅确认了（+）-belamide A（7）的结构和绝对构型，还确认了用于记录13 C NMR光谱，13 C NMR光谱数据相关性和天然belamide A的旋光度数据的溶剂。 （7）已被修改。
• N-methyl N-carboxyanhydride: an unexpected by-product when coupling boc-n-methyl amino acids
  作者：Eric Frérot、Jacques Coste、Joël Poncet、Patrick Jouin、Bertrand Castro

  DOI：10.1016/s0040-4039(00)78866-6

  日期：1992.5

  Activation of Boc-amino acids and Boc-N-methyl amino acids leads to the corresponding NCA. This side reaction explains the low yields obtained when coupling N-methyl amino acids. It was not observed with the Z- or Fmoc-protective groups.
• Shimagaki, Masayuki; Koshiji, Hiroko; Oishi, Takeshi, Phosphorus and Sulfur and the Related Elements, 1983, vol. 16, p. 45 - 58
  作者：Shimagaki, Masayuki、Koshiji, Hiroko、Oishi, Takeshi

  DOI：——

  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.