2-(2-methoxy-2-oxoethyl)-3-methylbut-2-enoic acid | 164364-44-7

• 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: 2-(2-methoxy-2-oxoethyl)-3-methylbut-2-enoic acid
• 英文别名: 4-methyl (1-methylethylidene)butanedioate
• CAS: 164364-44-7
• 化学式: C₈H₁₂O₄
• 分子量: 172.181
• InChiKey: HNRBMBFOADTSPS-UHFFFAOYSA-N

物化性质

• 熔点：
  97 °C
• 沸点：
  315.9±25.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2-methoxy-2-oxoethyl)-3-methylbut-2-enoic acid 在 4-二甲氨基吡啶 、 (Sa,S)-[(C₈H₁₂)Ir(P(3,5-(tert-butyl)2C₆H₃)2C₈H₇CC₈H₇C₃NOH₃(benzyl))][tetrakis[3,5-bis(trifluoromethyl)phenyl]borate] 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 60.0 ℃ 、607.99 kPa 条件下， 反应 25.0h， 生成
  参考文献：
  名称：

  四取代烯烃对铱催化的α，β-不饱和羧酸的铱催化对映选择性加氢

  摘要：

  已经开发出由手性螺铱配合物催化的具有四取代烯烃的α，β-不饱和羧酸的高效不对称加氢，用于制备具有优异对映选择性（至多99％ee）的手性α-取代的羧酸。

  DOI：

  10.1021/ol401593a
• 作为产物：
  描述：

  3-(methoxycarbonyl)-4-methylpent-3-enoic acid 在 sodium hydroxide 、 乙酰氯 作用下， 以 水 为溶剂， 反应 12.33h， 生成 2-(2-methoxy-2-oxoethyl)-3-methylbut-2-enoic acid
  参考文献：
  名称：

  Hydroxamic Acids as Potent Inhibitors of Endothelin-Converting Enzyme from Human Bronchiolar Smooth Muscle

  摘要：

  Hydroxamic acids 6a-h, derived from malonyl amino acids, and 25a-d, derived from succinyl amino acids, were synthesized as inhibitors of human bronchiolar smooth muscle endothelin-converting enzyme (HBSM ECE). Several unexpected side reactions were discovered, particularly in the synthesis of hydroxamates derived from succinates. In vitro evaluation against human bronchiolar ECE revealed that in all cases hydroxamates derived from malonate were more potent than hydroxamates derived from succinate. Isopropyl and isobutyl P-1' side chains were suitable; omission of the P-1' Side chain seriously diminished potency. In the P-2' position, several amino acids gave potent malonate-derived hydroxamate inhibitors (6b,d-h, IC50 = 0.2-6.8 nM), and beta-Ala provided an extremely potent inhibitor (6c, IC50 = 0.01 nM). C-terminus carboxylates are much more potent ECE inhibitors than the corresponding amides. Most of the hydroxamates were also potent inhibitors of thermolysin and neutral endopeptidase (NEP); however, the P-2' beta-Ala derivative 6c uniquely inhibited HBSM ECE much more potently than NEP.

  DOI：

  10.1021/jm00012a011

文献信息

• Conjugate addition of nitroalkanes to dimethyl maleate. Regioselective formation of both monoesters of 2-alkylsuccinic acids
  作者：Roberto Ballini、Giovanna Bosica、Alessandro Palmieri、Marino Petrini、Claudio Pierantozzi

  DOI：10.1016/s0040-4020(03)01175-x

  日期：2003.9

  Diesters of (E)-2-alkylidenesuccinic acids obtained by conjugate addition of nitroalkanes to dimethyl maleate can be selectively monohydrolyzed at the more reactive carboxyl group to the corresponding half-ester. Alternatively, total hydrolysis to the diacid allows a subsequent selective methyl esterification of the alkanoic carboxyl group to give the other regioisomeric half-ester. 2-Alkylsuccinic

  通过将硝基烷烃共轭加成到马来酸二甲酯中而获得的（E）-2-亚烷基琥珀酸的二酯可以在反应性更高的羧基上选择性地单水解成相应的半酯。可选择地，全部水解为二酸允许链烷羧基的随后的选择性甲基酯化，以给出其他区域异构的半酯。可以通过不饱和衍生物的催化加氢最终获得2-烷基琥珀酸单酯。
• Modulation of taxane binding to tubulin curved and straight conformations by systematic 3′N modification provides for improved microtubule binding, persistent cytotoxicity and in vivo potency
  作者：Yuntao Ma、Fernando Josa-Prado、Jacob Nathaniel Essif、Shuqi Liu、Shuo Li、Daniel Lucena-Agell、Peter YW. Chan、Kenneth Goossens、Rafael Hortigüela、Ruth Matesanz、Yingjie Wang、Federico Gago、Hongbo Wang、April Risinger、J. Fernando Diaz、Wei-Shuo Fang

  DOI：10.1016/j.ejmech.2023.115668

  日期：2023.11

  in locking tubulin in the s-conformation. A representative compound bearing an acrylamide moiety (2h) exhibited increased binding affinity to the unassembled tubulin c-conformation and less cytotoxicity than paclitaxel. Further exploration of chemical space around 2h afforded a new series 3, in which derivatives such as 3l bind more tightly to both the s- and c-conformations of tubulin compared to

  紫杉烷类微管稳定剂是最有效和最广泛使用的化疗药物之一。紫杉烷类的抗癌活性源于其通过选择性识别未组装微管蛋白中的弯曲（c-）构象（与组装微管蛋白中的直（s-）构象相比）来诱导微管蛋白组装的能力。我们首先设计并合成了一系列带有共价基团的3'N修饰的紫杉烷。我们没有发现共价紫杉烷，而是发现了一系列非共价紫杉烷2 ，其中 3'N 侧链由于其将微管蛋白锁定在 s 构象中的作用而被发现对于细胞毒性至关重要。带有丙烯酰胺部分的代表性化合物 ( 2h ) 与紫杉醇相比，对未组装的微管蛋白 c 构象具有更高的结合亲和力，并且细胞毒性更低。对2h左右化学空间的进一步探索提供了新的系列3，其中与紫杉醇相比， 3l等衍生物与微管蛋白的 s 和 c 构象结合更紧密，从而更有效地促进微管蛋白聚合，并具有更大的持久性。药物洗脱后对乳腺癌细胞的体外功效。尽管与紫杉醇相比，3l也具有改善的体内效力，但它也与增加的全身毒性有
• GUPTA, GEETA;BANERJEE, SHUBHRA, INDIAN J. CHEM. B , 29,(1990) N, C. 787-790
  作者：GUPTA, GEETA、BANERJEE, SHUBHRA

  DOI：——

  日期：——
• Iridium-Catalyzed Enantioselective Hydrogenation of α,β-Unsaturated Carboxylic Acids with Tetrasubstituted Olefins
  作者：Song Song、Shou-Fei Zhu、Yu Li、Qi-Lin Zhou

  DOI：10.1021/ol401593a

  日期：2013.7.19

  A highly efficient asymmetric hydrogenation of α,β-unsaturated carboxylic acids with tetrasubstituted olefin catalyzed by chiral spiro iridium complexes has been developed for the preparation of chiral α-substituted carboxylic acids in excellent enantioselectivities (up to 99% ee).

  已经开发出由手性螺铱配合物催化的具有四取代烯烃的α，β-不饱和羧酸的高效不对称加氢，用于制备具有优异对映选择性（至多99％ee）的手性α-取代的羧酸。
• Hydroxamic Acids as Potent Inhibitors of Endothelin-Converting Enzyme from Human Bronchiolar Smooth Muscle
  作者：Ron Bihovsky、Barry L. Levinson、Rivka C. Loewi、Paul W. Erhardt、Mark A. Polokoff

  DOI：10.1021/jm00012a011

  日期：1995.6

  Hydroxamic acids 6a-h, derived from malonyl amino acids, and 25a-d, derived from succinyl amino acids, were synthesized as inhibitors of human bronchiolar smooth muscle endothelin-converting enzyme (HBSM ECE). Several unexpected side reactions were discovered, particularly in the synthesis of hydroxamates derived from succinates. In vitro evaluation against human bronchiolar ECE revealed that in all cases hydroxamates derived from malonate were more potent than hydroxamates derived from succinate. Isopropyl and isobutyl P-1' side chains were suitable; omission of the P-1' Side chain seriously diminished potency. In the P-2' position, several amino acids gave potent malonate-derived hydroxamate inhibitors (6b,d-h, IC50 = 0.2-6.8 nM), and beta-Ala provided an extremely potent inhibitor (6c, IC50 = 0.01 nM). C-terminus carboxylates are much more potent ECE inhibitors than the corresponding amides. Most of the hydroxamates were also potent inhibitors of thermolysin and neutral endopeptidase (NEP); however, the P-2' beta-Ala derivative 6c uniquely inhibited HBSM ECE much more potently than NEP.