(2S,3S)-2-甲基-3-({[(2-甲基-2-丙基)氧基]羰基}氨基)丁酸 | 186494-09-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: (2S,3S)-2-甲基-3-({[(2-甲基-2-丙基)氧基]羰基}氨基)丁酸
• 英文名称: Boc-[(S,S)-β^2,3-hAla]-CO₂H
• 英文别名: (2S,3S)-3-([(tert-butoxy)carbonyl]amino)-2-methylbutanoicacid；(2S,3S)-2-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 186494-09-7
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: VZHAMECIWIQGRU-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-甲基-3-({[(2-甲基-2-丙基)氧基]羰基}氨基)丁酸 在 N-甲基吗啉 、 ammonium hydroxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium aluminium tetrahydride 、 乙醇 、 双氧水 、 三乙酰氧基硼氢化钠 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 、 sodium hydroxide 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 二甲基亚砜 、 1,2-二氯乙烷 、 甲苯 为溶剂， 生成 (15R,16S)-5,5,9,15,16-pentamethyl-7-oxo-2,13,17-triazatetracyclo[16.3.1.02,10.03,8]docosa-1(22),3(8),9,18,20-pentaene-19-carboxamide
  参考文献：
  名称：

  Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model

  摘要：

  An extension of our previously reported series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to the tether provided analogs that show increased potency in binding as well as cell-proliferation assays and, more importantly, are stable toward microsomes. We wish to disclose the discovery of a macrocycle which showed impressive biomarker activity 24-h post dosing and which demonstrated prolonged exposure in tumors. When studied in a lung cancer xenograft model, the compound demonstrated significant tumor size reduction. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.102
• 作为产物：
  描述：

  trans-2-Benzyl-3,4-dimethylisoxazolidin-5-one 在 palladium on carbon 、 氢气 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 (2S,3S)-2-甲基-3-({[(2-甲基-2-丙基)氧基]羰基}氨基)丁酸
  参考文献：
  名称：

  Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model

  摘要：

  An extension of our previously reported series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to the tether provided analogs that show increased potency in binding as well as cell-proliferation assays and, more importantly, are stable toward microsomes. We wish to disclose the discovery of a macrocycle which showed impressive biomarker activity 24-h post dosing and which demonstrated prolonged exposure in tumors. When studied in a lung cancer xenograft model, the compound demonstrated significant tumor size reduction. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.102

文献信息

• Thermodynamic Scale of β-Amino Acid Residue Propensities for an α-Helix-like Conformation
  作者：Brian F. Fisher、Seong Ho Hong、Samuel H. Gellman

  DOI：10.1021/jacs.8b05162

  日期：2018.8.1

  These measurements depend on formation of a parallel coiled-coil tertiary structure when two peptide segments become linked by thioester formation. One peptide segment contains a "guest" site that accommodates diverse β residues and is distal to the coiled-coil interface. We find that helix propensity is influenced by side chain placement within the β residue [β3 (side chain adjacent to nitrogen) slightly

  硫醇-硫酯交换系统已被用于测量不同 β-氨基酸残基参与α-螺旋状构象的倾向。当两个肽段通过硫酯形成连接时，这些测量取决于平行卷曲螺旋三级结构的形成。一个肽段包含一个“客体”位点，可容纳不同的 β 残基，位于卷曲螺旋界面的远端。我们发现螺旋倾向受 β 残基内侧链位置的影响 [β3（与氮相邻的侧链）相对于 β2（与羰基相邻的侧链）略微有利]。先前公认的由五元环掺入产生的螺旋稳定性被量化。
• ?2- and ?3-Peptides with Proteinaceous Side Chains: Synthesis and solution structures of constitutional isomers, a novel helical secondary structure and the influence of solvation and hydrophobic interactions on folding
  作者：Dieter Seebach、Stefan Abele、Karl Gademann、Gilles Guichard、Tobias Hintermann、Bernhard Jaun、Jennifer L. Matthews、J�rg V. Schreiber、Lukas Oberer、Ulrich Hommel、Hans Widmer

  DOI：10.1002/hlca.19980810513

  日期：——

  the previously prepared β-peptides (35–39) showed NH/ND exchange rates (in MeOH at room temperature) with τ1/2 values of up to 60 days, unrivalled by short chain α-peptides. All β-peptides 1–7 were designed to be able to attain the previously described 31-helical structure (Figs. 1 and 2). CD Measurements (Fig. 4), indicating a new secondary structure of certain β-peptides constructed of β2- and β3-amino

  对映体纯β-氨基酸为Ala，Val取代，和Leu的在2-或3-位上的侧链的衍生物（β 2 -和β 3 -氨基酸，RESP），以及与在这两个取代基2-位和3-位（β 2,3 -氨基酸的，像-构型）已经制备（化合物8 - 17）和结合（通过逐步合成和片段耦合，中间体24 - 34）到β-化十六- ， β-庚肽和β-十二肽（1 – 17）。新的和一些先前制备的β肽（35 – 39）显示了NH / ND交换速率（室温下在MeOH中），其τ1 /2值长达60天，这是短链α肽无法比拟的。所有的β肽1至7被设计为能够获得先前描述的3 1螺旋结构（图1和2）。CD测量（图4），表明β的构建某些β肽的新的二级结构2 -和β 3 -氨基酸，通过详细的NMR溶液结构分析确认：一个β 2 -heptapeptide（2C）和β 2,3- -hexapeptide（图7c），由于具有3 1螺旋结构（图6和7），而到β
• Probing the Helical Secondary Structure of Short-Chain ?-Peptides
  作者：Dieter Seebach、Paola E. Ciceri、Mark Overhand、Bernhard Jaun、Dario Rigo、Lukas Oberer、Ulrich Hommel、Ren� Amstutz、Hans Widmer

  DOI：10.1002/hlca.19960790802

  日期：1996.12.11

  u-(S,S)-β-HAla(αMe)-β-HVal-β-HAla- β-HLeu-OH (22), with a central (2S,3S)-3-amino-2-methylbutanoic-acid residue, confirm the helical structure of such β-peptides (previously discovered in pyridine solution) (Fig.3 and Tables 1–5). The CD spectra of helical β-peptides, the residues of which were prepared by (retentive) Arndt-Eistert homologation of the (S)- or L-α-amino acids, show a trough at 215 nm

  可以通过检查模型（图1和2）来定义3个1肽螺旋的稳定性的结构先决条件：3-氨基酸残基的2位和3位侧向非H取代基允许使用螺旋形的，螺旋形的则是禁止的。为了检验这一预测，我们合成了一系列七肽衍生物Boc-（β-HVal-β-HAla-β-HLeu-Xaa-β-HVal-β-HAla-β-HLeu）-OMe 13-22（ Xaa =α-或β-氨基酸残基）和带有中央（S）-3-羟基丁酸残基的X-二肽25（Xaa = –OCH（Me）CH 2 C（O）–）（方案1 3）。β-六肽H（-β-HVal-β-HAla-β-HLeu）2 -OH（1）和甲醇的β-六肽甲醇溶液的详细NMR分析（DQF-COSY，HSQC，HMBC，ROESY和TOCSY实验）β-七肽H-β-HVal-β-HAla-β-HLeu-（S，S）-β-HAla（αMe）-β-HVal-β-HAla-β-HLeu-OH（22） （2 S，3
• Determination of Enantiomer Purity ofβ- andγ-Amino Acids by NMR Analysis of Diastereoisomeric Palladium Complexes
  作者：Andreas Böhm、Dieter Seebach

  DOI：10.1002/1522-2675(20001220)83:12<3262::aid-hlca3262>3.0.co;2-p

  日期：2000.12.20

  Like alpha -amino acids, beta- and gamma -amino acids form spirobicyclic complexes (see 2 and 3) by reaction with the chiral di-mu -chlorobis2-[1-dimethylamino-xN)-ethyl]phenyl-xC}dipalladium complexes 1 under basic conditions (Scheme 1 and X-ray structures in Fig. I). The diastereoisomeric complexes formed with mixtures of enantiomers of either the amino acids or the dichloro-dipalladium complexes give rise to marked chemical-shift differences in the H-1- and C-13-NMR spectra (Figs. 2-4) to allow determination of the enantiomer purities. A simple procedure is described by which beta- and gamma -amino acids (which may be generated in situ from Boc- or Fmoc-protected precursors) are converted to the Pd complexes and subjected to NMR measurements. The effects of solvent, temperature, and variation of the aryl group in the chiral derivatizing Pd reagent are described (Figs. 4 and 5). The methyl esters of B-amino acids can also be employed, forming diastereoisomeric chloro[(amino-xN)aryl-xC][(amino-xN)alkanoate]palladium complexes 6 for determining enantiomer ratios (Scheme 6). The new method has great scope, as demonstrated for beta (2)-, beta (3), beta (2,3)-, beta (2,2,3)-, gamma (2)-, gamma (3)-, gamma (4)-, and gamma (2,3,4)- amino acid derivatives.