4-甲基-2-氧代戊酸苄酯 | 96136-13-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-甲基-2-氧代戊酸苄酯
• 英文名称: benzyl 4-methyl-2-oxo-pentanoate
• 英文别名: 4-methyl-2-oxo-pentanoic phenylmethyl ester acid；Benzyl 4-methyl-2-oxopentanoate
• CAS: 96136-13-9
• 化学式: C₁₃H₁₆O₃
• 分子量: 220.268
• InChiKey: SOVNRTNKFRLUDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2918300090

反应信息

• 作为反应物：
  描述：

  4-甲基-2-氧代戊酸苄酯 在 palladium on activated charcoal 氢气 、 sodium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 、 乙醇 为溶剂， 25.0 ℃ 、405.3 kPa 条件下， 反应 20.0h， 生成 N-(1(S)-(tert-Butyloxycarbonyl)-3-phenylpropyl)-L-leucine
  参考文献：
  名称：

  Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement

  摘要：

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.

  DOI：

  10.1021/jm00088a006
• 作为产物：
  描述：

  4-甲基-2-氧代戊酸乙酯 在 草酰氯 、 水 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 生成 4-甲基-2-氧代戊酸苄酯
  参考文献：
  名称：

  使用金鸡纳生物碱酰胺催化剂将硫化膦不对称共轭加成到 α-取代的 β-硝基丙烯酸酯上

  摘要：

  含手性膦的氨基酸是药物化合物中有用的基序。在这项研究中，我们开发了硫化膦与α-取代的β-硝基丙烯酸酯的不对称共轭加成，以合成具有手性四取代碳中心的含膦氨基酸前体。该方法底物范围宽，所得产物可转化为多种手性化合物。通过计算分析阐明了对映选择性的起源。

  DOI：

  10.1021/acs.orglett.4c02643

文献信息

• Non-peptide renin inhibitors
  申请人：Abbott Laboratories

  公开号：US05268374A1

  公开（公告）日：1993-12-07

  The present invention relates to renin inhibiting compounds of the formula: ##STR1##

  这项发明涉及公式为的肾素抑制化合物：##STR1##
• Activation of 1,2-Keto Esters with Takemoto’s Catalyst toward Michael Addition to Nitroalkenes
  作者：Wilfried Raimondi、Olivier Baslé、Thierry Constantieux、Damien Bonne、Jean Rodriguez

  DOI：10.1002/adsc.201100739

  日期：2012.3

  When activated with Takemoto’s catalyst, 1,2‐keto esters constitute versatile nucleophiles in the Michael addition reaction with nitroalkenes affording synthetically valuable, optically active anti‐adducts in very good yields and high enantiomeric excesses.

  当用Takemoto的催化剂活化时，1,2-酮酸酯会在Michael加成反应中与硝基烯烃形成通用的亲核试剂，从而以非常高的收率和很高的对映体过量提供合成上有价值的光学活性抗加合物。
• A Compact Chemical Miniature of a Holoenzyme, Coenzyme NADH Linked Dehydrogenase. Design and Synthesis of Bridged NADH Models and Their Highly Enantioselective Reduction¹
  作者：Nobuhiro Kanomata、Tadashi Nakata

  DOI：10.1021/ja992990y

  日期：2000.5.1

  pyridine-formation reaction of formyl-substituted (vinylimino)phosphorane 4 with methyl propiolate. The bridged NADH models 10a−c effected excellent biomimetic reduction at various temperatures in the presence of magnesium ion to achieve both the enantioselective and stereospecific reduction of the pyruvate analogues 12u−z into chiral lactate analogues 13u−z with 88−99% ee. The high enantioselectivity was almost

  需要辅酶 NADH 的 L-乳酸脱氢酶在无氧糖酵解中催化丙酮酸对映选择性还原为 L-乳酸。作为第一个同手性 ansa 型 NADH 模型，我们设计了桥接 NADH 模型 10a-c，其具有对吡啶并烷结构，用于严格模拟 NADH 生物不对称还原中氢转移的立体特异性。这些模型是从相应的桥接烟酸酯 5 中分几个步骤合成的，该桥接烟酸酯 5 通过我们新的甲酰基取代（乙烯基亚氨基）正膦 4 与丙炔酸甲酯的吡啶形成反应制备。桥接的 NADH 模型 10a-c 在镁离子存在的情况下在不同温度下实现了出色的仿生还原，以实现丙酮酸类似物 12u-z 的对映选择性和立体定向还原成手性乳酸类似物 13u-z，具有 88-99% ee。高对映选择性几乎完全取决于 10a-c 的平面手性，而不取决于它们的取代基的性质。
• Amino acid derivatives inhibiting extracellular matrix metalloproteinase and TNF alpha release
  申请人：Chiesi Farmaceutici S.p.A.

  公开号：US06344457B1

  公开（公告）日：2002-02-05

  The invention concerns compounds of general formula (X) in which Y represents in particular —CONHOH, R1 represents in particular a C1-C5 alkyl group, AA represents an amino acid, or an amino acid sequence, and R3 represents in particular a group of formula —NH—(CH2)2—SCH3. The invention also concerns the pharmaceutical compositions containing them, and the methods for obtaining them.

  该发明涉及一般式（X）的化合物，其中Y特指—CONHOH，R1特指C1-C5烷基，AA代表氨基酸或氨基酸序列，R3特指一种—NH—(CH2)2—SCH3的基团。该发明还涉及含有这些化合物的药物组合物，以及获得它们的方法。
• Highly water-soluble metalloproteinase inhibitors
  申请人：Fuji Yakuhin Kogyo Kabushiki Kaisha

  公开号：US06147114A1

  公开（公告）日：2000-11-14

  New compounds of the general formula (I) ##STR1## (wherein R.sup.1 is a hydrogen atom, or a hydroxyl, aryl (C.sub.1 -C.sub.6)alkylene or --A--SOn--B group (A is a (C.sub.1 -C.sub.6) alkylene group; B is a (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) acyl, aryl or heterocyclyl group; n is 0, 1 or 2), R.sup.2 is a hydrogen atom, or a (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) alkyloxy 10 or (C.sub.1 -C.sub.6) alkylthio group, R.sup.3 and R.sup.4 are identical or different, representing a hydrogen atom, or a (C.sub.1 -C.sub.6) alkyl, aryl or aryl(C.sub.1 -C.sub.6)alkylene group, R.sup.5 is a --Y--C or C group (Y is a (C.sub.1 -C.sub.6) alkylene group, an oxygen atom, an imino group or a (C.sub.1 -C.sub.6) alkyleneimino group, C is a sulfonic acid, phosphonic acid, amidino, (C.sub.1 -C.sub.6) acyl, acylimidoyl, diphosphonomethine or dicarboxymethine group), and R.sup.6 is a hydrogen atom, or a nonsubstituted or substituted benzyl, trialkylsilyl, tert-butyldiphenylsilyl, tetrahydropyranyl or tert-butyl group) or stereoisomers thereof, and pharmaceutically acceptable salts thereof and solvates thereof, and the process for the preparation thereof, and metalloproteinase inhibitors which comprise one or more compounds selected from those compounds as effective ingredients and inhibit matrix metalloproteinases (MMPs) and/or TNF-.alpha. converting enzyme. Furthermore, the preparation intermediates to obtain the compounds of the formula (I) and the process for the preparation.

  通用式(I)的新化合物##STR1##（其中R.sup.1是氢原子，或羟基，芳基（C.sub.1-C.sub.6）烷基或-A-SOn-B基团（A是（C.sub.1-C.sub.6）烷基基团；B是（C.sub.1-C.sub.6）烷基，（C.sub.1-C.sub.6）酰基，芳基或杂环基团；n为0, 1或2），R.sup.2是氢原子，或（C.sub.1-C.sub.6）烷基，（C.sub.1-C.sub.6）烷氧基或（C.sub.1-C.sub.6）烷硫基团，R.sup.3和R.sup.4相同或不同，代表氢原子，或（C.sub.1-C.sub.6）烷基，芳基或芳基（C.sub.1-C.sub.6）烷基团，R.sup.5是--Y--C或C基团（Y是（C.sub.1-C.sub.6）烷基基团，氧原子，亚胺基或（C.sub.1-C.sub.6）烷基亚胺基团，C是磺酸，膦酸，酰胺，（C.sub.1-C.sub.6）酰基，酰亚胺基，二磷酰亚甲基或二羧甲亚基团），R.sup.6是氢原子，或非取代或取代的苄基，三烷基硅基，叔丁基二苯基硅基，四氢吡喃基或叔丁基基团）或其立体异构体，以及其药学上可接受的盐和溶剂合物，以及其制备方法，以及包括从这些化合物中选择的一个或多个有效成分的金属蛋白酶抑制剂，并抑制基质金属蛋白酶（MMPs）和/或TNF-.alpha.转化酶。此外，用于获得通式(I)化合物的制备中间体和制备方法。