methyl (3S)-3-(N-tert-butoxycarbonylamino)-5-phenylpentanoate | 158807-52-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl (3S)-3-(N-tert-butoxycarbonylamino)-5-phenylpentanoate
• 英文别名: (S)-methyl 3-(tert-butoxycarbonyl)-5-phenylpentanoate；methyl (3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-5-phenylpentanoate
• CAS: 158807-52-4
• 化学式: C₁₇H₂₅NO₄
• 分子量: 307.39
• InChiKey: QLXPLYPDAYMKQG-AWEZNQCLSA-N

物化性质

• 熔点：
  54-55 °C
• 沸点：
  429.8±45.0 °C(Predicted)
• 密度：
  1.070±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (3S)-3-(N-tert-butoxycarbonylamino)-5-phenylpentanoate 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 二氯甲烷 为溶剂， 反应 3.7h， 生成
  参考文献：
  名称：

  Identification and Initial Structure−Activity Relationships of a Novel Class of Nonpeptide Inhibitors of Blood Coagulation Factor Xa

  摘要：

  The discovery and some of the basic structure-activity relationships of a series of novel nonpeptide inhibitors of blood coagulation Factor Xa is described. These inhibitors are functionalized p-alanines, exemplified by 2a. Docking experiments placing 2a in the active site of Factor Xa implied that the Most expeditious route to enhancing in vitro potency was to modify the group occupying the S3 site of the enzyme. Increasing the hydrophobic contacts between the inhibitor and the enzyme in this region led to 8, which has served as the prototype for this series. In addition, an enantioselective synthesis of these substituted p-alanines was also developed.

  DOI：

  10.1021/jm970482y
• 作为产物：
  描述：

  Boc-L-高苯丙氨酸 在 N-甲基吗啉 、 silver benzoate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.25h， 生成 methyl (3S)-3-(N-tert-butoxycarbonylamino)-5-phenylpentanoate
  参考文献：
  名称：

  Identification and Initial Structure−Activity Relationships of a Novel Class of Nonpeptide Inhibitors of Blood Coagulation Factor Xa

  摘要：

  The discovery and some of the basic structure-activity relationships of a series of novel nonpeptide inhibitors of blood coagulation Factor Xa is described. These inhibitors are functionalized p-alanines, exemplified by 2a. Docking experiments placing 2a in the active site of Factor Xa implied that the Most expeditious route to enhancing in vitro potency was to modify the group occupying the S3 site of the enzyme. Increasing the hydrophobic contacts between the inhibitor and the enzyme in this region led to 8, which has served as the prototype for this series. In addition, an enantioselective synthesis of these substituted p-alanines was also developed.

  DOI：

  10.1021/jm970482y

文献信息

• Divergent reaction pathways in amine additions to β-lactone electrophiles. An application to β-peptide synthesis
  作者：Scott G. Nelson、Keith L. Spencer、Wing S. Cheung、Steven J. Mamie

  DOI：10.1016/s0040-4020(02)00722-6

  日期：2002.8

  β-Lactone electrophiles are subject to regioselective addition–elimination (AE) or SN2 ring opening with various nitrogen-based nucleophiles. Primary and secondary amines promote AE ring opening to deliver products that are the functional equivalent of amide aldol adducts. Azide and sulfonamide anion nucleophiles engender SN2 lactone ring opening to deliver N-protected β-amino acid derivatives. These

  β-内酯亲电体会与多种基于氮的亲核体发生区域选择性加成-消除（AE）或S N 2开环。伯胺和仲胺可促进AE开环，从而提供功能上与酰胺醇醛加合物相同的产品。叠氮化物和磺酰胺阴离子亲核试剂使S N 2内酯开环传递N保护的β-氨基酸衍生物。这些依赖亲核试剂的开环途径，再加上通过酰基卤-醛环缩合反应获得的富含大量庚酮的β-内酯的便捷途径，构成了不对称有机合成的通用方法。还描述了该反应技术在基于从AAC开环序列中出现的旋光性β-叠氮酸的β肽合成新方法中的应用。
• Catalytic Asymmetric Mannich Reactions of Sulfonylacetates
  作者：Carlo Cassani、Luca Bernardi、Francesco Fini、Alfredo Ricci

  DOI：10.1002/anie.200900701

  日期：2009.7.20

  synthetic equivalents of a variety of α‐carboxylate anions. Phase‐transfer catalysis (PTC) enabled their mild deprotonation and catalytic asymmetric addition to highly reactive imines generated in situ from α‐amidosulfones (see scheme; Pg=protecting group). The synthetic utility of the products was demonstrated by their straightforward transformation into a range of β‐amino acid derivatives.

  砜与砜：芳基磺酰乙酸盐可以看成是各种α-羧酸根阴离子的合成等价物。相转移催化（PTC）使它们能够轻度去质子化，并催化不对称添加到α-酰胺基砜现场生成的高反应性亚胺上（见方案； Pg =保护基）。通过将其直接转化为一系列β-氨基酸衍生物，证明了该产品的合成效用。
• Serine–threonine protein phosphatase inhibitors derived from nodularin: role of the 2-methyl and 3-diene groups in the Adda residue and the effect of macrocyclic conformational restraint
  作者：Michael E. O'Donnell、Jonathan Sanvoisin、David Gani

  DOI：10.1039/b100402f

  日期：——

  In order to probe the effect upon macrocycle conformation and PP1cat enzyme inhibition of structural changes to nodularin, specific replacements for the Adda residue were introduced. Two new analogues, cyclo[-(3S,E)-3-phenylethenyl-3-aminopropanoyl-α-(R)-Glu-α-OH-γ-Sar-(R)-Asp-α-OH-β-(S)-Phe-] 19a and cyclo[-(2S,3S,E)-2-methyl-3-phenylethenyl-3-aminopropanoyl-β-(R)-Glu-α-OH-γ-Sar-(R)-Asp-α-OH-β-(S)-Phe-] 19b were prepared incorporating previously optimised preparative protocols [see previous article, K. L. Webster, A. B. Maude, M. E. O'Donnell, A. P. Mehrotra and D. Gani, J. Chem. Soc., Perkin Trans. 1 (DOI: 10.1039/b100401h)], and these differed only at C-2 of the Adda residue. The presence of a (2S)-methyl group in compound 19b stabilised the trans-rotameric form of the (2R)-Glu-γ-Sar amide bond in solution as determined by NMR spectroscopic analysis (trans–cis; 10:1), and enhanced efficacy as a PP1cat inhibitor by 20-fold over compound 19a. The methyl homologue displayed a competitive mode of inhibition, with respect to the substrate Ac-Arg-Arg-Thr(P)-Val-Ala and displayed a Ki value of 206 ± 30 μmol dm−3. Substitution of the Sar residue in the methyl homologue by (2S)-Pro gave a competitive inhibitor of similar efficacy (Ki = 400 ± 75 μmol dm−3). The proline analogue 22 existed as a 6:1 mixture of trans–cis rotamers. Evidently the trans-rotamer of the (2S)-Pro-containing compound differed in conformational structure compared to the sarcosine-containing variant, only close to the site of the substitution. A structural model for the inhibition of PP1cat and a strategy for the selective inhibition of PP1 over PP2A are discussed within the context of the results.

  PP1cat酶抑制剂对环状结构的影响
• A concise enantioselective synthesis of allylamines and N-boc-β-amino acids
  作者：Montserrat Alcón、Marc Canas、Marta Poch、Albert Moyano、Miguel A. Pericàs、Antoni Riera

  DOI：10.1016/s0040-4039(00)76766-9

  日期：1994.3

  A new and efficient enantioselective synthesis of allylamines and N-Boc-β-amino acids has been developed. Starting from enantiomerically enriched N-diphenylmethyl-3-amino-1,2-diols, allylamines are easily obtained by a Corey-Hopkins deoxygenative protocol. After a change in the nitrogen protecting group, the resulting N-Boc allylamines are converted into β-amino acids by hydroboration with 9-BBN followed

  已经开发了烯丙胺和N -Boc-β-氨基酸的新的和有效的对映选择性合成。从对映体富集的N-二苯基甲基-3-氨基-1,2-二醇开始，烯丙基胺很容易通过Corey-Hopkins脱氧方案获得。改变氮保护基团后，通过用9-BBN进行硼氢化，然后在DMF中用PDC氧化，将所得的N- Boc烯丙基胺转化为β-氨基酸。
• Catalytic Enantioselective Conjugate Addition of Carbamates
  作者：Claudio Palomo、Mikel Oiarbide、Rajkumar Halder、Michael Kelso、Enrique Gómez-Bengoa、Jesús M. García

  DOI：10.1021/ja047004e

  日期：2004.8.1

  Catalytic, asymmetric conjugate addition of carbamates to enoyl systems has been realized for the first time, providing a two-step access to virtually enantiopure N-protected beta-amino acids.