N-Boc-Val-Met-OH | 68683-72-7

• 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-Boc-Val-Met-OH
• 英文别名: (S)-2-((S)-2-tert-butoxycarbonylamino-3-methylbutyrylamino)-4-methylsulfanylbutyric acid；N-(tert-Butoxycarbonyl)-L-valyl-L-methionine；(2S)-2-[[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-4-methylsulfanylbutanoic acid
• CAS: 68683-72-7
• 化学式: C₁₅H₂₈N₂O₅S
• 分子量: 348.464
• InChiKey: WTBGFWUPURGUPU-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-Boc-Val-Met-OH 在 对苯二腈 、 菲 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.0h， 生成 tert-butyl N-[(2S)-1-[[(2S)-1-[(1-cyano-4-methylpentan-3-yl)amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Direct modification of tripeptides using photoinduced decarboxylative radical reactions

  摘要：

  In order to explore the applicability of photoinduced electron transfer (PET) promoted decarboxylative reactions to the direct modification of peptides, a study was performed to assess the influence of amino acid side chains on photoreactions of N-terminal protected tripeptides. Photoinduced decarboxylation reactions of tripeptides, which are composed of central amino acids that possess alkyl, phenyl, thioether, hydroxy, and amide containing side chains, in the presence or absence of acrylonitrile and a thiol were found to proceed smoothly to give the corresponding radical addition, H-abstraction, and substitution products. Although photoreactions of tripeptides containing central amino acids with phenol and indole (Tyr and Trp) moieties do not take place efficiently, appropriate protection of these groups enables the substrates to undergo smooth photoinduced decarboxylative reactions. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.12.075
• 作为产物：
  描述：

  N-{[(2-甲基-2-丙基)氧基]羰基}-L-缬氨酰-L-蛋氨酸甲酯 在 水 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 生成 N-Boc-Val-Met-OH
  参考文献：
  名称：

  用于合成非天然 α-氨基酸的脱氢丙氨酸的生物相容性光诱导烷基化

  摘要：

  描述了脱氢丙氨酸的位点选择性烷基化以获取受保护的非天然氨基酸。该协议的特点是所用烷基的广泛性质、温和的条件和官能团兼容性。该协议进一步扩展到访问肽、药物的后期功能化和对映体富集的氨基酸。

  DOI：

  10.1021/acs.orglett.1c01781

文献信息

• Synthesis of potent BACE-1 inhibitors incorporating a hydroxyethylene isostere as central core
  作者：Fredrik Wångsell、Karin Gustafsson、Ingemar Kvarnström、Neera Borkakoti、Michael Edlund、Katarina Jansson、Jimmy Lindberg、Anders Hallberg、Åsa Rosenquist、Bertil Samuelsson

  DOI：10.1016/j.ejmech.2009.11.013

  日期：2010.3

  herein describe the design and synthesis of a series of BACE-1 inhibitors incorporating a P1-substituted hydroxylethylene transition state isostere. The synthetic route starting from commercially available carbohydrates yielded a pivotal lactone intermediate with excellent stereochemical control which subsequently could be diversified at the P1-position. The final inhibitors were optimized using three

  我们在本文中描述了一系列掺入P1-取代的羟乙烯过渡态等排体的BACE-1抑制剂的设计和合成。从可商购获得的碳水化合物开始的合成路线产生了具有出色立体化学控制能力的关键内酯中间体，该中间体随后可在P1位置多样化。使用三种不同的胺对最终的抑制剂进行了优化，以提供在P2'-P3'位置的残基，使用三种不同的酸在P2-P3的位置提供残基。此外，我们报告了合成抑制剂中P1'-甲基取代基的立体化学偏好。在体外BACE-1分析中评估了所有抑制剂，其中最有效的抑制剂34-（R）表现出BACE-1 IC50值的3.1 nM。
• Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR
  作者：Jason Lamar、Jingdan Hu、Ana Belen Bueno、Hsiu-Chiung Yang、Deqi Guo、James D. Copp、James McGee、Bruce Gitter、David Timm、Patrick May、James McCarthy、Shu-Hui Chen

  DOI：10.1016/j.bmcl.2003.09.084

  日期：2004.1

  We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC50 = 45 nM) and cellular activity (IC50 = 0.4 muM). (C) 2003 Elsevier Ltd. All rights reserved.
• Design, synthesis and SAR of potent statine-based BACE-1 inhibitors: Exploration of P1 phenoxy and benzyloxy residues
  作者：Marcus Bäck、Jonas Nyhlén、Ingemar Kvarnström、Sara Appelgren、Neera Borkakoti、Katarina Jansson、Jimmy Lindberg、Susanne Nyström、Anders Hallberg、Åsa Rosenquist、Bertil Samuelsson

  DOI：10.1016/j.bmc.2008.09.041

  日期：2008.11

  Several BACE-1 inhibitors with low nanomolar level activities, encompassing a statine-based core structure with phenyloxymethyl- and benzyloxymethyl residues in the P1 position, are presented. The novel P1 modification introduced to allow the facile exploration of the S1 binding pocket of BACE-1, delivered highly promising inhibitors.
• Biocompatible Photoinduced Alkylation of Dehydroalanine for the Synthesis of Unnatural α-Amino Acids
  作者：José A. C. Delgado、José T. M. Correia、Emanuele F. Pissinati、Márcio W. Paixão

  DOI：10.1021/acs.orglett.1c01781

  日期：2021.7.2

  A site-selective alkylation of dehydroalanine to access protected unnatural amino acids is described. The protocol is characterized by the wide nature of alkyl radicals employed, mild conditions, and functional group compatibility. This protocol is further extended to access peptides, late-stage functionalization of pharmaceuticals, and enantioenriched amino acids.

  描述了脱氢丙氨酸的位点选择性烷基化以获取受保护的非天然氨基酸。该协议的特点是所用烷基的广泛性质、温和的条件和官能团兼容性。该协议进一步扩展到访问肽、药物的后期功能化和对映体富集的氨基酸。
• Direct modification of tripeptides using photoinduced decarboxylative radical reactions
  作者：Kousuke Maeda、Hikaru Saito、Kazuyuki Osaka、Keisuke Nishikawa、Mai Sugie、Toshio Morita、Ichiro Takahashi、Yasuharu Yoshimi

  DOI：10.1016/j.tet.2014.12.075

  日期：2015.2

  In order to explore the applicability of photoinduced electron transfer (PET) promoted decarboxylative reactions to the direct modification of peptides, a study was performed to assess the influence of amino acid side chains on photoreactions of N-terminal protected tripeptides. Photoinduced decarboxylation reactions of tripeptides, which are composed of central amino acids that possess alkyl, phenyl, thioether, hydroxy, and amide containing side chains, in the presence or absence of acrylonitrile and a thiol were found to proceed smoothly to give the corresponding radical addition, H-abstraction, and substitution products. Although photoreactions of tripeptides containing central amino acids with phenol and indole (Tyr and Trp) moieties do not take place efficiently, appropriate protection of these groups enables the substrates to undergo smooth photoinduced decarboxylative reactions. (C) 2014 Elsevier Ltd. All rights reserved.