(S)-2-Benzyloxycarbonylamino-3-cyclohexyl-propionic acid methyl ester | 113828-93-6

• 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)-2-Benzyloxycarbonylamino-3-cyclohexyl-propionic acid methyl ester
• 英文别名: Methyl (I+/-S)-I+/--[[(phenylmethoxy)carbonyl]amino]cyclohexanepropanoate；methyl (2S)-3-cyclohexyl-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 113828-93-6
• 化学式: C₁₈H₂₅NO₄
• 分子量: 319.401
• InChiKey: GPCBBYINDBESQY-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  (S)-2-Benzyloxycarbonylamino-3-cyclohexyl-propionic acid methyl ester 在 palladium on activated charcoal 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 2-{(2-tert-butoxycarbonylamino-ethyl)-[(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-acetyl]-amino}-3-cyclohexyl-propionic acid methyl ester
  参考文献：
  名称：

  利用Et-DuPHOS-Rh +烯醇酯的加氢合成对映体纯的骨架烷基取代的肽核酸

  摘要：

  通过掺入Et-DuPHOS-Rh +烯醇酯的催化不对称氢化产生的新型α-氨基酸，合成了一系列对映体纯的烷基取代的肽核酸（PNA）单体。图选项

  DOI：

  10.1016/s0040-4039(99)00518-3
• 作为产物：
  描述：

  N-环己基-beta-丙氨酸 在 4-二甲氨基吡啶 、 Carica papaya lipase 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 环己烷 为溶剂， 反应 24.0h， 生成 (S)-2-Benzyloxycarbonylamino-3-cyclohexyl-propionic acid methyl ester
  参考文献：
  名称：

  Resolution of non-protein amino acids via Carica papaya lipase-catalyzed enantioselective transesterification

  摘要：

  Carica papaya lipase-catalyzed transesterification of the 2,2,2-ti-ifluoroethyl esters of N-benzyloxycarbonylated DL-amino acids carrying aliphatic side chains proceeded smoothly and, in almost all the cases, enantiospecifically (E = > 200), affording the L-methyl esters and leaving the D-trifluoroethyl esters intact. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.06.037

文献信息

• Design, Synthesis, and Evaluation of Novel Prodrugs of Transition State Inhibitors of Norovirus 3CL Protease
  作者：Anushka C. Galasiti Kankanamalage、Yunjeong Kim、Athri D. Rathnayake、Kevin R. Alliston、Michelle M. Butler、Steven C. Cardinale、Terry L. Bowlin、William C. Groutas、Kyeong-Ok Chang

  DOI：10.1021/acs.jmedchem.7b00497

  日期：2017.7.27

  Ester and carbamate prodrugs of aldehyde bisulfite adduct inhibitors were synthesized in order to improve their pharmacokinetic and pharmacodynamic properties. The inhibitory activity of the compounds against norovirus 3C-like protease in enzyme and cell-based assays was determined. The ester and carbamate prodrugs displayed equivalent potency to those of the precursor aldehyde bisulfite adducts and

  醛亚硫酸氢盐加合物抑制剂的酯和氨基甲酸酯前药被合成，以改善其药代动力学和药效学性质。在酶和基于细胞的测定中，确定了化合物对诺如病毒3C样蛋白酶的抑制活性。酯和氨基甲酸酯前药显示出与前体醛亚硫酸氢盐加合物和前体醛相同的效力。此外，发现酯的裂解速率取决于烷基链长。产生的前药显示出低细胞毒性和令人满意的肝微粒体稳定性和血浆蛋白结合。
• <i>Carica papaya</i>Lipase Catalysed Resolution of β-Amino Esters for the Highly Enantioselective Synthesis of (<i>S</i>)-Dapoxetine
  作者：Pengyong You、Jian Qiu、Erzheng Su、Dongzhi Wei

  DOI：10.1002/ejoc.201201055

  日期：2013.1

  CPL-catalysed resolution. The mechanism of the CPL-catalysed enantioselective alcoholoysis of the amino acids is discussed to delineate the substrate requirements for CPL-catalysed resolution. Finally, the reaction was scaled up, and the products were separated and obtained in good yields (≥ 80 %). The (S)-3-amino-3-phenylpropanoic acid obtained was used as a key chiral intermediate in the synthesis

  通过番木瓜脂肪酶 (CPL) 催化对映选择性醇解相应的外消旋 N 保护的 2,2,2-三氟乙酯在有机溶剂中的有效合成（S）-3-氨基-3-苯基丙酸对映​​体. 高对映选择性（E > 200）通过两种策略实现，涉及底物工程和反应条件的优化。基于一系列氨基酸的拆分，发现底物的结构对CPL催化的拆分具有深远的影响。通过将常规甲酯转换为活化的三氟乙酯，显着提高了对映选择性和反应速率。在考虑空间效应时，取代的苯基和氨基对于 CPL 催化的拆分不应都很大。讨论了 CPL 催化的氨基酸对映选择性醇解的机制，以描述 CPL 催化拆分的底物要求。最后，放大反应，分离产物并以良好的收率（≥ 80 %）获得。获得的 (S)-3-氨基-3-苯基丙酸用作合成 (S)-达泊西汀的关键手性中间体，对映体过量 (> 99 %)。
• Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors
  作者：Sivakoteswara Rao Mandadapu、Mallikarjuna Reddy Gunnam、Kok-Chuan Tiew、Roxanne Adeline Z. Uy、Allan M. Prior、Kevin R. Alliston、Duy H. Hua、Yunjeong Kim、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.bmcl.2012.11.026

  日期：2013.1

  Noroviruses are the most common cause of acute viral gastroenteritis, accounting for >21 million cases annually in the US alone. Norovirus infections constitute an important health problem for which there are no specific antiviral therapeutics or vaccines. In this study, a series of bisulfite adducts derived from representative transition state inhibitors (dipeptidyl aldehydes and alpha-ketoamides) was synthesized and shown to exhibit anti-norovirus activity in a cell-based replicon system. The ED50 of the most effective inhibitor was 60 nM. This study demonstrates for the first time the utilization of bisulfite adducts of transition state inhibitors in the inhibition of norovirus 3C-like protease in vitro and in a cell-based replicon system. The approach described herein can be extended to the synthesis of the bisulfite adducts of other classes of transition state inhibitors of serine and cysteine proteases, such as alpha-ketoheterocycles and alpha-ketoesters. (C) 2012 Elsevier Ltd. All rights reserved.
• Potent inhibition of norovirus by dipeptidyl α-hydroxyphosphonate transition state mimics
  作者：Sivakoteswara Rao Mandadapu、Mallikarjuna Reddy Gunnam、Anushka C. Galasiti Kankanamalage、Roxanne Adeline Z. Uy、Kevin R. Alliston、Gerald H. Lushington、Yunjeong Kim、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.bmcl.2013.08.073

  日期：2013.11

  The design, synthesis, and evaluation of a series of dipeptidyl alpha-hydroxyphosphonates is reported. The synthesized compounds displayed high anti-norovirus activity in a cell-based replicon system, as well as high enzyme selectivity. (C) 2013 Elsevier Ltd. All rights reserved.
• Structure-Guided Design and Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. Structure–Activity Relationships and Biochemical, X-ray Crystallographic, Cell-Based, and In Vivo Studies
  作者：Anushka C. Galasiti Kankanamalage、Yunjeong Kim、Pathum M. Weerawarna、Roxanne Adeline Z. Uy、Vishnu C. Damalanka、Sivakoteswara Rao Mandadapu、Kevin R. Alliston、Nurjahan Mehzabeen、Kevin P. Battaile、Scott Lovell、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1021/jm5019934

  日期：2015.4.9

  Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of antinorovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection.