methyl α-isobutylacrylate | 3070-69-7

• 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: methyl α-isobutylacrylate
• 英文别名: Methyl-α-isobutylacrylat；methyl 2-(2-methylpropyl)acrylate；Methyl 4-methyl-2-methylidenepentanoate
• CAS: 3070-69-7
• 化学式: C₈H₁₄O₂
• mdl: MFCD25962107
• 分子量: 142.198
• InChiKey: FVAWMVZVWUHHOB-UHFFFAOYSA-N

物化性质

• 沸点：
  162.9±9.0 °C(Predicted)
• 密度：
  0.892±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.625
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl α-isobutylacrylate 在 N-甲基吗啉 、 borate buffer 、 氨 、 牛血清白蛋白 、 氯甲酸异丁酯 作用下， 以 甲醇 、 乙醚 、 乙腈 为溶剂， 反应 28.05h， 生成 N-2(S)-<<<(N-carbobenzoxyamino)methyl>methoxyphosphinyl>methyl>-4-methylpentanamide
  参考文献：
  名称：

  Differential binding energy: a detailed evaluation of the influence of hydrogen-bonding and hydrophobic groups on the inhibition of thermolysin by phosphorus-containing inhibitors

  摘要：

  Two series of phosphorus-containing peptide analogues, 3 (Cbz-Gly-psi(PO2-CH2)Leu-Xaa) and 4 (Cbz-Gly-psi-(PO2-NH)Leu-psi[CO2]Xaa), have been synthesized and evaluated as inhibitors of the zinc endopeptidase thermolysin. In comparison with the previously reported phosphonamidates 1, the phosphinates 3 lose only 0.1 kcal/mol in binding affinity, whereas the depsipeptides 4 are bound 2.7 kcal/mol more weakly; these values are contrasted to the 4.0 kcal/mol reduction in binding affinity observed for the phosphonates 2 (Cbz-Gly-psi(PO2-O)Leu-Xaa) in comparison to 1 (Cbz-Gly-psi(PO2-NH)Leu-Xaa). The observed effects are interpreted through consideration of the differences in active-site and solvent interactions. For the comparison between the diamides 1 and the depsipeptides 4, a full accounting of the balance between these interactions can be approached. The arylphosphonates 5 (Aryl-psi(PO2-O)Leu-Leu) were synthesized and evaluated to investigate the importance of phosphonate basicity on the overall binding affinity of these zinc-coordinating inhibitors; the inhibitor K(i) values were found to be independent of phosphonate p(K)a, indicating that the basicity of the phosphonate moiety exerts counterbalancing effects on the energies of zinc coordination and solvation. For analysis of the influence of structural variations on observed affinity, the definition of "differential binding energy" is introduced as a practical alternative to the concept of "intrinsic binding energy".

  DOI：

  10.1021/ja00001a043
• 作为产物：
  描述：

  甲醇 、 异丁基丙二酸二乙酯 、 聚合甲醛 在 吡啶 、 氢氧化钾 作用下， 生成 methyl α-isobutylacrylate
  参考文献：
  名称：

  Metzger, Juergen O.; Klenke, Kurt, Chemische Berichte, 1990, vol. 123, # 4, p. 875 - 879

  摘要：

  DOI：

文献信息

• Development of Catalytic Asymmetric 1,4-Addition and [3 + 2] Cycloaddition Reactions Using Chiral Calcium Complexes
  作者：Tetsu Tsubogo、Susumu Saito、Kazutaka Seki、Yasuhiro Yamashita、Shu̅ Kobayashi

  DOI：10.1021/ja8032058

  日期：2008.10.8

  4-addition and [3 + 2] cycloaddition reactions using chiral calcium species prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3

  已经开发了使用由异丙醇钙和手性双恶唑啉配体制备的手性钙物质的催化不对称 1,4-加成和 [3 + 2] 环加成反应。甘氨酸席夫碱与丙烯酸酯反应以高产率和高对映选择性提供 1,4-加成产物谷氨酸衍生物。在研究 1,4-加成反应期间，我们意外地发现 [3 + 2] 环加成发生在与巴豆酸酯衍生物的反应中，以高产率和高对映选择性提供取代的吡咯烷衍生物。基于这一发现，我们研究了不对称的 [3 + 2] 环加成，结果表明，获得了具有高非对映选择性和对映选择性的几种含有连续立体异构叔和季碳中心的旋光取代吡咯烷衍生物。此外，已经使用这种 [3 + 2] 环加成反应合成了丙型肝炎病毒 RNA 依赖性聚合酶抑制剂的光学活性吡咯烷核心和潜在的有效抗病毒剂。NMR 光谱分析和非线性效应实验中对映选择性的非放大观察表明，形成了具有阴离子配体的单体钙物质作为活性催化剂。提出了 [3 + 2] 环加成的逐步机制，包括 1
• .beta.-thiopropionyl-aminoacid derivatives and their use as
  申请人：SmithKline Beecham p.l.c.

  公开号：US06048852A1

  公开（公告）日：2000-04-11

  A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a .beta.-lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, ##STR1## wherein: R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group; R.sub.1 is hydrogen, (C.sub.1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C.sub.1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C.sub.1-6)alkylcarbonyloxy, (C.sub.1-6)alkoxycarbonyl, formyl or (C.sub.1-6)alkylcarbonyl group, (C.sub.3-7)cycloalkyl, (C.sub.3-7)cycloalkyl(C.sub.2-6)alkyl, (C.sub.2-6)alkenyl, (C.sub.2-6)alkynyl, aryl, aryl(C.sub.1-6)alkyl, heterocyclyl or heterocyclyl(C.sub.1-6)alkyl; R.sub.2 is hydrogen, (C.sub.1-6)alkyl or aryl(C.sub.1-6)alkyl; R.sub.3 is hydrogen, (C.sub.1-6)alkyl optionally substituted by up to three halogen atoms, (C.sub.3-7)cycloalkyl, fused aryl(C.sub.3-7)cycloalkyl, (C.sub.3-7)cycloalkyl(C.sub.2-6)alkyl, (C.sub.2-6)alkenyl, (C.sub.2-6)alkynyl, aryl, aryl-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n, heterocyclyl or heterocyclyl-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n, where m is 0 to 3, n is 1 to 3, each R.sub.10 and R.sub.11 is independently hydrogen or (C.sub.1-4)alkyl and X is O, S(O).sub.x where x is 0-2, or a bond; R.sub.4 is hydrogen, or an in vivo hydrolysable acyl group; and R.sub.5 and R.sub.6 are independently hydrogen and (C.sub.1-6)alkyl or together represent (CH.sub.2).sub.p where p is 2 to 5. Some compounds are claimed per se.

  一种治疗人类或动物细菌感染的方法，包括与β-内酰胺类抗生素联合给药，给予公式(I)的氨基酸衍生物的治疗有效量或其药用可接受的盐、溶剂化合物或体内可水解酯的治疗有效量，其中：R为氢、形成盐的阳离子或体内可水解酯形成基团；R.sub.1为氢、(C.sub.1-6)烷基，可选地被高达三个卤素原子或巯基、(C.sub.1-6)烷氧基、羟基、氨基、硝基、羧基、(C.sub.1-6)烷基羰氧基、(C.sub.1-6)烷氧羰基、甲酰基或(C.sub.1-6)烷基羰基取代，(C.sub.3-7)环烷基，(C.sub.3-7)环烷基(C.sub.2-6)烷基，(C.sub.2-6)烯基，(C.sub.2-6)炔基，芳基，芳基(C.sub.1-6)烷基，杂环烷基或杂环烷基(C.sub.1-6)烷基；R.sub.2为氢，(C.sub.1-6)烷基或芳基(C.sub.1-6)烷基；R.sub.3为氢，(C.sub.1-6)烷基，可选地被高达三个卤素原子取代，(C.sub.3-7)环烷基，融合的芳基(C.sub.3-7)环烷基，(C.sub.3-7)环烷基(C.sub.2-6)烷基，(C.sub.2-6)烯基，(C.sub.2-6)炔基，芳基，芳基-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n，杂环烷基或杂环烷基-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n，其中m为0至3，n为1至3，每个R.sub.10和R.sub.11独立地为氢或(C.sub.1-4)烷基，X为O，S(O).sub.x，其中x为0-2，或键；R.sub.4为氢，或体内可水解的酰基；R.sub.5和R.sub.6独立地为氢和(C.sub.1-6)烷基，或一起代表(CH.sub.2).sub.p，其中p为2至5。一些化合物本身被要求。
• Phosphinic acid inhibitors of D-alanyl-D-alanine ligase
  作者：William H. Parsons、Arthur A. Patchett、Herbert G. Bull、William R. Schoen、David Taub、Jacqueline Davidson、Patricia L. Combs、James P. Springer、Hans Gadebusch

  DOI：10.1021/jm00117a017

  日期：1988.9

  We report the synthesis of a series of phosphinic acid dipeptide analogues, NH2CH(R1)PO(OH)CH2CH(R2)CO2H, related to DAla-DAla. The best of these compounds are potent, essentially irreversible inhibitors of DAla-DAla ligase, and their preferred stereochemistry was shown by chiral synthesis of (1(S)-aminoethyl)(2(R)-carboxy-1-n-propyl)phosphinic acid, 12b, and by X-ray crystallography of its derivative

  我们报告了与DAla-DAla有关的一系列次膦酸二肽类似物NH2CH（R1）PO（OH）CH2CH（R2）CO2H的合成。这些化合物中最好的是有效的，基本上不可逆的DAla-DAla连接酶抑制剂，并且通过（1（S）-氨基乙基）（2（R）-羧基-1-n-丙基）次膦酸酯的手性合成显示了其优选的立体化学酸12b，并通过X射线晶体学分析其衍生物苄基[1（S）-[（苄氧羰基）-氨基]乙基]（2（R）-羰甲氧基-1-丙基）次膦酸酯13两个中心的DAla-DAla配置。提出了通过这些化合物抑制DAla-DAla连接酶的机制，涉及在该酶的活性位点内ATP依赖性磷酸化抑制剂的形成。尽管它们的光谱包括革兰氏阳性和革兰氏阴性易感生物，但这些化合物的抗菌活性中等。（1（S）-氨基乙基）[2-羧基-2（R）-（甲硫基）-1-乙基]次膦酸3e表现出最佳的抗菌活性，其9的MIC为4-128微克/ mL。一组11种细菌。
• The Most Potent Organophosphorus Inhibitors of Leucine Aminopeptidase. Structure-Based Design, Chemistry, and Activity
  作者：Jolanta Grembecka、Artur Mucha、Tomasz Cierpicki、Paweł Kafarski

  DOI：10.1021/jm030795v

  日期：2003.6.1

  phosphinate dipeptide analogues, which were synthesized and evaluated as inhibitors of the enzyme. The in vitro kinetic studies for the phosphinate dipeptide analogues revealed that these compounds belong to the group of the most effective LAP inhibitors found so far. Their further modification at the P1 position resulted in more active inhibitors, hPheP[CH(2)]Phe and hPheP[CH(2)]Tyr (K(i) values 66 nM and

  描述了一类新型的非常有效的细胞溶质亮氨酸氨基肽酶（LAP）抑制剂，该酶是金属蛋白酶家族的成员。牛晶状亮氨酸氨肽酶与亮氨酸的膦酸类似物（LeuP）配合的X射线结构用于新型LAP抑制剂的基于结构的设计，并用于分析其与酶结合位点的相互作用。通过修饰LeuP结构中的膦酸基团以寻找结合在酶S'侧的取代基来设计抑制剂。这产生了两类化合物，膦酰胺和次膦酸酯二肽类似物，它们被合成并被评估为酶的抑制剂。次膦酸酯二肽类似物的体外动力学研究表明，这些化合物属于迄今为止发现的最有效的LAP抑制剂。它们在P1位置的进一步修饰产生了更具活性的抑制剂hPheP [CH（2）] Phe和hPheP [CH（2）] Tyr（四种非对映异构体的混合物的K（i）值分别为66 nM和67 nM ）。如果考虑所有包含模拟LAP催化的反应过渡态的磷原子的化合物，则这些抑制剂对酶的结合亲和力最高。为了评估设计的LAP抑制剂的选择性，对
• Catalytic asymmetric synthesis of 5-membered alicyclic α-quaternary β-amino acids <i>via</i> [3 + 2]-photocycloaddition of α-substituted acrylates
  作者：Yuto Kimura、Daisuke Uraguchi、Takashi Ooi

  DOI：10.1039/d1ob00126d

  日期：——

  stereoselective [3 + 2]-cycloaddition of cyclopropylurea with α-substituted acrylates. This protocol provides straightforward access to a variety of stereochemically defined 5-membered alicyclic α-quaternary β-amino acids, useful building blocks of β-peptides and peptidomimetics.

  阳离子铱多吡啶基配合物和手性硼酸盐的光催化活性盐能促进环丙基脲与α-取代的丙烯酸酯的高度立体选择性[3 + 2]-环加成。该协议可直接访问各种立体化学定义的5元脂环族α-季基β-氨基酸，β肽和拟肽的有用组成部分。