ethyl N-tert-butyloxycarbonyl-2-amino-5-hexenoate | 756498-97-2

• 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: ethyl N-tert-butyloxycarbonyl-2-amino-5-hexenoate
• 英文别名: ethyl 2-N-(tert-butoxycarbonyl)-2-aminohex-5-enoate；(RS)-ethyl 2 N-(tert-butoxycarbonyl)-2-amino-5-hexenoate；ethyl 2-((tert-butoxycarbonyl)amino)hex-5-enoate；Ethyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]hex-5-enoate
• CAS: 756498-97-2
• 化学式: C₁₃H₂₃NO₄
• 分子量: 257.33
• InChiKey: RHVRFNSXOWUSCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.41
• 重原子数：
  18.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  64.63
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  ethyl N-tert-butyloxycarbonyl-2-amino-5-hexenoate 在 N-甲基吗啉 、 盐酸 、 lithium hydroxide 、 lithium aluminium tetrahydride 、 双氧水 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 ((S)-2-{(1R,2S,5S)-2-[1-(Carbamoyl-hydroxy-methyl)-pent-4-enylcarbamoyl]-6,6-dimethyl-3-aza-bicyclo[3.1.0]hex-3-yl}-1-cyclohexyl-2-oxo-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of (1R,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor:  A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection

  摘要：

  Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.

  DOI：

  10.1021/jm060325b
• 作为产物：
  描述：

  2-氧代-5-己酸乙酯 在 zinc trifluoromethanesulfonate 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 20.5h， 生成 ethyl N-tert-butyloxycarbonyl-2-amino-5-hexenoate
  参考文献：
  名称：

  模仿酶促氨基转移：尝试理解和发展手性α-氨基酸的催化不对称方法。

  摘要：

  试图通过机理研究和在不对称催化与酶促反应之间架起桥梁，并发展了一种手性路易斯酸催化的伯胺催化α-酮基酯的催化和对映选择性方法的氨基化反应，作为氨基转移酶的模型。使用伯胺氮源（例如吡nitrogen胺和4-吡啶甲基胺），不同的路易斯酸可以催化α-酮基酯的半氨基转移。使用氘标记的化合物对路易斯酸催化的半反式氨基转移的机理研究表明，氘原子在α-氨基酸衍生物的多个位置上掺入，表明α-酮酯的烯醇在其中起着重要的作用。反应路径。催化对映选择性反应取决于溶剂的pKa值，因为对映选择性仅在相对于甲醇具有高pKa值的溶剂中获得。但是，较强的酸性条件通常可提供较好的收率，但对映选择性差。筛选了一系列手性路易斯酸作为对映选择性半氨基转移反应的催化剂，并获得了中等收率和高达46％ee的对映选择性。

  DOI：

  10.1039/b404381b

文献信息

• [EN] COMPOUNDS AS CDK2/4/6 INHIBITORS<br/>[FR] COMPOSÉS EN TANT QU'INHIBITEURS DE CDK2/4/6
  申请人：FOCHON PHARMACEUTICALS LTD

  公开号：WO2021170076A1

  公开（公告）日：2021-09-02

  Provided are certain CDK2/4/6 inhibitors, pharmaceutical compositions thereof, and methods of use thereof.

  提供了某些CDK2/4/6抑制剂，其药物组成物以及使用方法。
• α-Chymotrypsin and<scp>l</scp>-acylase aided synthesis of 5-hydroxypipecolic acid via Jacobsen's hydrolytic kinetic resolution of epoxy amino acids
  作者：Suvratha Krishnamurthy、Jalli Venkataprasad、Tarun Chand Vagvala、Tetsuji Moriguchi、Akihiko Tsuge

  DOI：10.1039/c5ra09207h

  日期：——

  used to synthesize racemic 2-amino-5-hexenoic acid. These racemic 2-amino-5-hexenoic acid (homoallylyglycine) derivatives were efficiently resolved aided by α-chymotrypsin or L-acylase, giving rise to L- and D-enantiomers. These isolated enantiomerically pure amino acids with tert-butoxycarbonyl (Boc) protection were oxidised with 3-chloroperbenzoic acid. The oxidation gave rise to inseparable diastereomeric

  丙二酸二乙酯衍生物用于合成外消旋的2-氨基-5-己酸。这些外消旋的2-氨基-5-己烯酸（homoallylyglycine）衍生物有效的解决由α胰凝乳蛋白酶或资助大号-acylase，产生大号-和d -对映体。将这些具有叔丁氧羰基（Boc）保护的对映体纯的氨基酸用3-氯过苯甲酸氧化。由于在C 5上新生成的手性中心，氧化产生了不可分割的非对映体环氧化物碳。通过将剩余的非对映异构体选择性转化为由Jacobsen水解动力学拆分（HKR）催化的二羟基化合物，可以分离出一种非对映异构体环氧化物。分离出的环氧化物被溴化锂区域选择性地攻击，得到邻卤代醇，而溴化物攻击末端的C 6碳。卤代醇的Boc脱保护通过游离胺攻击C 6碳而导致分子内环化，生成了5-羟基哌酸的单一异构体，在用Boc基团对胺进行重新保护后，毫不费力地回收了该异构体。同样，较早分离出的二羟基化合物在C 6处被碘转化为卤代醇。碳。通过用催化性Bu
• Synthesis of 5′-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5′ and sulfur atoms replaced by a vinyl or halovinyl unit
  作者：Stanislaw F. Wnuk、Pablo R. Sacasa、Elzbieta Lewandowska、Daniela Andrei、Sumin Cai、Ronald T. Borchardt

  DOI：10.1016/j.bmc.2008.04.017

  日期：2008.5

  Adenosine and uridine analogues functionalized with alkenyl or. uoroalkenyl chain at C5' were prepared employing cross-metathesis, Negishi couplings, and Wittig reactions. Metathesis of the protected 5'-deoxy-5'- methyleneadenosine or uridine analogues with six-carbon amino acids (homoallylglycines) in the presence of Grubbs catalysts gave nucleoside analogues with the C5'-C6' double bond. Alternatively, the Pd-catalyzed cross-coupling between the protected 5'-deoxy-5'-(iodomethylene) nucleosides and suitable alkylzinc bromides also provided analogues with alkenyl unit. Stereoselective Pd-catalyzed monoalkylation of 5'-(bromofluoromethylene)-5'-deoxyadenosine with alkylzinc bromides afforded adenosylhomocysteine analogues with a 6'-(fluoro) vinyl motif. The vinylic adenine nucleosides produced time-dependent inactivation of the S-adenosyl-L-homocysteine hydrolases. (C) 2008 Elsevier Ltd. All rights reserved.
• <i>S-</i>Adenosylhomocysteine Analogues with the Carbon-5‘ and Sulfur Atoms Replaced by a Vinyl Unit
  作者：Daniela Andrei、Stanislaw F. Wnuk

  DOI：10.1021/ol062026m

  日期：2006.10.1

  Cross-metathesis of suitably protected 5'-deoxy-5'-methyleneadenosines with racemic and chiral N-Boc-protected six-carbon amino acids bearing a terminal double bond in the presence of the Hoveyda-Grubbs catalyst gave adenosylhomocysteine analogues with the C5'-C6' double bond. Bromination with pyridinium tribromide and dehydrobromination with DBU followed by standard deprotections yielded the 5'-(bromo) vinyl analogue.