(2R)-2-(benzoylamino)-3-methylbutyric acid methyl ester | 1492-13-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2R)-2-(benzoylamino)-3-methylbutyric acid methyl ester
• 英文别名: methyl (2R)-(N-benzoyl)-amino-3-methylbutyrate；(2R)-N-Benzoylvaline methyl ester；(R)-N-benzoylvaline methyl ester；N-benzoyl-D-valine methyl ester；N-benzoyl-D-valine methyl ester；N-Benzoyl-D-valin-methylester；methyl (2R)-2-benzamido-3-methylbutanoate
• CAS: 1492-13-3
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: ORTKTVHSBAJGTR-LLVKDONJSA-N

物化性质

• 熔点：
  108-109 °C
• 沸点：
  398.0±25.0 °C(Predicted)
• 密度：
  1.086±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R)-2-(benzoylamino)-3-methylbutyric acid methyl ester 在 甲醇 、 乙醚 、 一水合肼 、 溶剂黄146 、 sodium nitrite 作用下， 反应 2.0h， 生成 N-((S)-α-benzoylamino-isobutylcarbamoyl)-D-valine methyl ester
  参考文献：
  名称：

  The Isomeric Dipeptides of Valine Including a Correction¹

  摘要：

  DOI：

  10.1021/ja01160a053
• 作为产物：
  描述：

  苯甲酰氯 在 硫酸 、 sodium hydroxide 作用下， 反应 3.0h， 生成 (2R)-2-(benzoylamino)-3-methylbutyric acid methyl ester
  参考文献：
  名称：

  2-Aroylamino-3-methylbutanohydrazide 的一些腙：作为 HIV-1 立体选择性抑制剂的合成、分子建模研究和鉴定

  摘要：

  根据我们的抗病毒药物开发尝试，合成了带有氨基酸侧链的酰腙衍生物，以评估它们对各种病毒的抗病毒活性。在这些化合物中，8S、11S 和 12S 显示出抗 HIV-1 活性，抑制浓度为 50% (IC50) = 123.8 µM（选择性指数，SI > 3），IC50 = 12.1 µM（SI > 29），IC50 =分别为 17.4 µM (SI > 19)。对映异构体 8R、11R 和 12R 对 HIV-1 毒株 IIIB 无活性。对 HIV-1 野生型有活性的腙 8S、11S 和 12S 对双突变 NNRTI 抗性菌株（K103N；Y181C）没有抑制作用。使用 HIV-1 RT 的腙结合新位点，对 8、11 和 12 的 R-和 S-对映异构体进行了分子对接计算。

  DOI：

  10.1002/ardp.201200311

文献信息

• Kinetic resolution of amines with enantiopure 3-N,N-diacylaminoquinazolin-4(3H)-ones
  作者：Al-Sehemi, Abdullah G.、Atkinson, Robert S.、Fawcett, John

  DOI：10.1039/b105917n

  日期：2002.1.7

  The title compounds (DAQs) are chiral when the two N-acyl groups are different because of the absence of rotation around the N–N bond (a chiral axis). Enantiopure DAQs have been obtained by incorporation of a chiral centre in enantiopure form either into the substituent at the Q2-position or into one of the N-acyl groups, or into both, followed by separation of diastereoisomers. This separation is unnecessary in one case because conversion of the N-monoacylaminoquinazolinone (MAQ) into the DAQ is completely diastereoselective. Neither is separation of diastereoisomers necessary with 3-[N,N-di-(S)-2-acetoxypropanoylamino]-2-diphenylmethylquinazolin-4(3H)-one 37a: this DAQ 37a has its N–N bond rendered a chiral axis by the bias in its imide moiety wholly in favour of one exo/endo conformation.The high chemoselectivity exhibited by N,N-diacetyl- or N,N-dibenzoylaminoquinazolinones in reaction with the less hindered of two secondary amines (pyrrolidine in the presence of 1 eq. of piperidine) has a stereoselective counterpart: reaction of the above enantiopure DAQs enantioselectively with racemic amines leading to kinetic resolution. Using 1 eq. of DAQ and 2 eq. of amine, both the derivatised and unreacted amine enantiomers are recovered with high enantiomeric excess (ee) (better than 90% ee in some cases). Some of the higher ees are found in the recovered amides where non-chemoselective attack on both N-acyl groups of the DAQ has occurred: from the opposite configurations of the amine component in the two amides and from the low enantiopurity of the recovered unreacted amine, reaction of each of the N-acyl groups with complementary enantiomers of the amine is occurring (parallel kinetic resolution).Although higher ees are, in general, obtained using secondary amines, high ees are obtained in some cases using 1-phenylethylamine and, in particular, amino acid esters (valine and alanine).The sense of enantioselectivity in the reactions of these DAQs with amines is controlled by the configuration of the N–N axis: replacing the Q group in an N-(S)-2-acetoxypropanoyl-N-acetyl-bearing DAQ by phthalimide, thus eliminating the N–N chiral axis, drastically reduces the level of kinetic resolution.

  标题化合物(DAQs)在两个N-酰基团不同时是手性的，因为N-N键（一个手性轴）缺乏旋转。通过将手性中心以手性形式引入Q2-位点的取代基或其中一个N-酰基团，或两者中，随后分离diastereoisomers，得到了纯对映体的DAQs。在一个情况下，这种分离是不必要的，因为将N-单酰胺基喹唑啉酮(MAQ)转化为DAQ是完全立体选择性的。对于3-[N,N-di-(S)-2-乙酰氧基丙酰胺基]-2-二苯甲基喹唑啉-4(3H)-酮37a，也不需要分离diastereoisomers：这个DAQ 37a通过其亚胺部分的偏向完全倾向于一个exo/endo构象，使其N-N键成为一个手性轴。N,N-二乙酰基或N,N-二苯甲酰氨基喹唑啉酮在与两个次级胺中较少受到阻碍的胺（在存在1 eq.的哌啶的情况下使用吡咯烷）反应时表现出高度的化学选择性，这在立体选择性上有对应：上述纯对映体的DAQs与外消旋胺反应，导致动力学拆分。使用1 eq.的DAQ和2 eq.的胺，衍生化的和未反应的胺对映体都以高对映体过量（ee）回收（在一些情况下优于90% ee）。在一些回收的酰胺中发现较高的ee，其中非化学选择性地攻击DAQ的两个N-酰基团：从两个酰胺中胺组分的相反构型和回收的未反应胺的低对映纯度，每个N-酰基团与胺的互补对映体反应（并行动态拆分）。尽管通常使用次级胺得到较高的ee，但在某些情况下使用1-苯乙胺，特别是氨基酸酯（缬氨酸和丙氨酸）得到高ee。这些DAQs与胺反应的对映选择性的方向受N-N轴配置的控制：在带有N-(S)-2-乙酰氧基丙酰基-N-乙酰基的DAQ中，通过用邻苯二甲酰亚胺替换Q组，从而消除N-N手性轴，显著降低了动力学拆分的水平。
• Application of the addition of triorganozincates to N-(tert-butanesulfinyl)imines to the enantioselective synthesis of α-amino acids
  作者：Raquel Almansa、David Guijarro、Miguel Yus

  DOI：10.1016/j.tetlet.2009.05.008

  日期：2009.7

  Highly enantiomerically enriched N-protected α-amino acids can be easily prepared from optically pure N-(tert-butanesulfinyl)imines by a four-step sequence involving: diastereoselective addition of a triorganozincate to the imine, removal of the sulfinyl group, benzoylation of the nitrogen atom of the obtained primary amine and oxidation of one of the substituents on the carbon atom α to the nitrogen

  高度对映体富集的N-保护的α-氨基酸可以很容易地由光学纯的N-（叔丁烷亚磺酰基）亚胺通过以下四个步骤序列制得：非对映选择性地向亚胺中添加三有机锌，亚磺酰基的去除，苯甲酰基的苯甲酰化获得的伯胺的氮原子被碳原子α上的取代基之一氧化成氮。在亚磺酰基手性助剂中使用相同的配置，具有（R）或（S可以通过选择亚胺和有机锌酸盐的适当组合来制备构型。具有高光学纯度的α，α-二取代的α-氨基酯也可以通过将三烷基锌酸酯非对映选择性地加成到α-亚氨基酯中来制备。
• Asymmetric electrochemical oxidation of 1,2-diols, aminoalcohols, and aminoaldehydes in the presence of chiral copper catalyst
  作者：Daishirou Minato、Hitomi Arimoto、Yoko Nagasue、Yosuke Demizu、Osamu Onomura

  DOI：10.1016/j.tet.2008.05.015

  日期：2008.7

  Asymmetric oxidation of 1,2-diols, aminoalcohols, and aminoaldehydes in the presence of copper(II) triflate and (R,R)-Ph-BOX was accomplished by electrochemical method using Br− as a mediator. This oxidation was applicable to kinetic resolution of racemic cis-cycloalkane-1,2-diols, aminoalcohols, and aminoaldehydes to afford optically active compounds with good to high enantioselectivity.

  在铜的存在下的1,2-二醇，氨基醇，氨基醛和不对称氧化（II），三氟甲磺酸和（- [R ，- [R）-Ph-BOX通过使用溴电化学方法来实现-作为介体。该氧化适用于外消旋的顺式-环烷烃-1，2-二醇，氨基醇和氨基醛的动力学拆分，以提供具有良好至高对映选择性的旋光化合物。
• Regioselectivity in formations of amidocarboxy-substituted free radicals
  作者：Christopher J. Easton、Michael P. Hay

  DOI：10.1039/c39850000425

  日期：——

  Deuterium isotope effects establish a direct contrest in regioselectivity in reaction of N-benzoylvaline methyl ester with sulphuryl chloride and N-bromosuccinimide, and are indicative of factors affecting production of amidocarboxy-type capto-dative free radicals.

  氘的同位素效应在N-苯甲酰缬氨酸甲酯与硫酰氯和N-溴代琥珀酰亚胺的反应中建立了区域选择性的直接竞争者，并且表明了影响酰胺基羧基型Capdative自由基产生的因素。
• Amide Skeletal Elongation via Amino Acid Insertion
  作者：Zhengqiang Liu、Lei Zhou、Wenbo H. Liu

  DOI：10.1002/chem.202301729

  日期：2023.8.15

  A new amide bond activation paradigm through amino acid insertion enabled by two tandem intramolecular rearrangements is reported. This strategy only requires stable and readily available amide and amino acid as the starting materials, which does not need any pre-functionalization as well as the isolation of reaction intermediates.

  报道了一种通过两个串联分子内重排实现的氨基酸插入的新酰胺键激活范例。该策略仅需要稳定且易于获得的酰胺和氨基酸作为起始原料，不需要任何预官能化以及反应中间体的分离。