(S)-N'-(3'-bromopropyl)-3-methyl-2-(N-tert-butyloxycarbonylamino)butyramide | 573968-40-8

• 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: (S)-N'-(3'-bromopropyl)-3-methyl-2-(N-tert-butyloxycarbonylamino)butyramide
• CAS: 573968-40-8
• 化学式: C₁₃H₂₅BrN₂O₃
• 分子量: 337.257
• InChiKey: GIWLKCCTYIORNK-JTQLQIEISA-N

物化性质

• 沸点：
  460.5±30.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  19.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  67.43
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-N'-(3'-bromopropyl)-3-methyl-2-(N-tert-butyloxycarbonylamino)butyramide 在 盐酸 、 四丁基碘化铵 、 caesium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.0h， 生成 (2R,3S)-3-{(S)-2-[(S)-2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-3-methyl-butyrylamino}-2-hydroxy-N-((8S,11S)-8-isopropyl-7,10-dioxo-2-oxa-6,9-diaza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-trien-11-yl)-4-phenyl-butyramide
  参考文献：
  名称：

  Design and synthesis of broad-Based mono- and bi- cyclic inhibitors of FIV and HIV proteases

  摘要：

  Based on the substrate transition state and our strategy to tackle the problem of drug resistance, a series of HIV/FIV protease (HIV/FIV PR) monocyclic inhibitors incorporating a 15- or 17-membered macrocycle with an equivalent P3 or P3' group and a unique unnatural amino acid, (2R, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid, have been designed and synthesized. In addition, based on the structure of TL3 with small P3/P3' group, we have synthesized two conformationally restricted bicyclic inhibitors containing the macrocycle, which mimic the P1/P1'-P3/P3' tripeptide [Phe-Val-Ala] of TL3. We have found that the contribution of the macrocycle in our monocyclic inhibitors is important to the overall activity, but the ring size does not affect the activity to a significant extent. Several inhibitors that were developed in this work, exhibit low nanomolar inhibitory activity against the wild-type HIV/FIV PR and found to be highly effective against some drug-resistant as well as TL3-resistant mutants of HIV PRs. Compound 15, in particular, is the most effective cyclic inhibitor in hand to inhibit FIV replication in tissue culture at a concentration of 1.0 mug/mL (1.2 muM). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00054-3
• 作为产物：
  描述：

  N-Boc-L-缬氨酸 、 3-溴丙胺氢溴酸盐 在 N-甲基吗啉 、 氯甲酸乙酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以92%的产率得到(S)-N'-(3'-bromopropyl)-3-methyl-2-(N-tert-butyloxycarbonylamino)butyramide
  参考文献：
  名称：

  Synthesis and Isolation of 5,6-Dihydro-4H-1,3-Oxazine Hydrobromides by Autocyclization of N-(3-Bromopropyl)amides

  摘要：

  5,6-Dihydro-4H-1,3-oxazine hydrobromides have been synthesized by the nucleophilic autocyclo-O-alkylation of N-(3-bromopropyl)amides under neutral conditions in chloroform. It is found that electron-donating amide alpha-substituents influence the autocyclization efficiency.

  DOI：

  10.1021/jo101955q

文献信息

• Accessing the disallowed conformations of peptides employing amide-to-imidate modification
  作者：Damodara N. Reddy、Ravula Thirupathi、Erode N. Prabhakaran

  DOI：10.1039/c1cc13515e

  日期：——

  Selective modification of the C-terminal amide in peptides to dihydrooxazine (a novel stable imidate isostere) by intramolecular nucleophilic cyclo-O-alkylation of the corresponding N-(3-bromopropyl)amides results in constraining of the C-terminal residue in natively disallowed conformations both in crystals and in solution.

  通过分子内亲核环氧烷基化反应，选择性地将肽的C末端酰胺修饰为二氢恶唑（一种新型稳定异氰酸酯类似物），即相应的N-(3-溴丙基)酰胺，导致在晶体和溶液中将C末端残基限制在天然情况下不允许的构象中。
• A New Class of Macrocyclic Receptors from <b><i>iota</i></b>-Peptides
  作者：Sang-Woo Kang、Chris M. Gothard、Santanu Maitra、Atia-tul-Wahab、James S. Nowick

  DOI：10.1021/ja0677970

  日期：2007.2.1

  This paper presents a new class of macrocycles and demonstrates the potential of these macrocycles to bind guests and to display different substituents in sequence. The macrocyclic iota-peptides (ι-peptides) 1 are based on the ι-amino acid aminodiphenylmethanecarboxylic acid (Adc). Adc can be thought of as an analogue of the α-amino acid glycine that has been enlarged fourfold, to 1.0 nm in length

  本文介绍了一类新的大环，并证明了这些大环结合客体和依次显示不同取代基的潜力。大环iota-肽(ι-肽)1基于ι-氨基酸氨基二苯基甲烷羧酸(Adc)。Adc 可以被认为是 α-氨基酸甘氨酸的类似物，通过将两个苯环插入主链键，该甘氨酸被放大了四倍，长度为 1.0 nm。Fmoc 保护的 Adc 变体 2 很容易在多克规模上以良好的产率制备，并且可用于通过在 2-氯三苯甲基树脂上固相合成受保护的线性 Adc 四聚体，然后进行大环化、脱保护来制备大环 ι-肽 1 , 和 RP-HPLC 纯化。环(AdcK)4 (1b) 在 DMSO-d6 溶液中的 1H NMR 谱仅显示一组共振，由具有四重对称性和所有反式酰胺键的“方形”构象异构体产生；D2O 中的频谱显示了与“方形”连接相关的共振……
• Design, synthesis, and biological evaluation of HIV/FIV protease inhibitors incorporating a conformationally constrained macrocycle with a small P3′ residue
  作者：Chi Ching Mak、Van-Duc Le、Ying-Chuan Lin、John H Elder、Chi-Huey Wong

  DOI：10.1016/s0960-894x(00)00641-7

  日期：2001.1

  A series of norstatine-based HIV/FIV protease inhibitors incorporating a 15-membered macrocycle as a mimic of the tripeptide (Ala-Val-Phe), a motif with a small P3' residue effective against the FIV protease and the drug-resistant HIV proteases, has been synthesized. It was found that the macrocycle is important to the overall activity of the inhibitors. Certain inhibitors were developed expressing low nanomolar inhibitory activity against the HIV/FIV proteases and they are also effective against some drug-resistant as well as TL3-resistant HIV proteases. (C) 2001 Elsevier Science Ltd. All rights reserved.