allyl benzyl malonate | 357209-89-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: allyl benzyl malonate
• 英文别名: 3-O-benzyl 1-O-prop-2-enyl propanedioate
• CAS: 357209-89-3
• 化学式: C₁₃H₁₄O₄
• 分子量: 234.252
• InChiKey: GWPKBUQCGBMRPS-UHFFFAOYSA-N

物化性质

• 沸点：
  316.2±22.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  allyl benzyl malonate 在 四氢吡咯 、 四(三苯基膦)钯 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 、 xylene 为溶剂， 反应 15.75h， 生成 (2R,5S)-5-amino-2-(benzyloxycarbonyl-methyl)-6-methyl-4-oxo-heptanoic acid
  参考文献：
  名称：

  Dipeptidomimetic Ketomethylene Isosteres as Pro-moieties for Drug Transport via the Human Intestinal Di-/Tripeptide Transporter hPEPT1:  Design, Synthesis, Stability, and Biological Investigations

  摘要：

  Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity for the di-/tripeptide transporter hPEPT1, and the transepithelial transport properties of the model prodrugs were investigated. ValPsi[COCH2]-Asp(OBn) was the compound with highest chemical stability in buffers at pH 6.0 and 7.4, with half-lives of 190 and 43 h, respectively. All five compounds showed high affinity for hPEPT1 (K-i values < 1 mM), and PhePsi[COCH2]Asp(OBn) and ValPsi[COCH2]Asp(OBn) had the highest affinities with K-i values of 68 and 19 muM, respectively. Am hPEPT1-mediated transport component was demonstrated for the transepithelial transport of three compounds, a finding that was corroborated by hPEPT1-mediated intracellular uptake. The results indicate that the stabilized Phe-Asp and Val-Asp derivatives are promising pro-moieties in a prodrug approach targeting hPEPT1.

  DOI：

  10.1021/jm040780c
• 作为产物：
  描述：

  丙二酸单苯甲酯 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.5h， 生成 allyl benzyl malonate
  参考文献：
  名称：

  提供复杂的β-内酯的多组分，对映选择性的Michael–Michael-Aldol-β-内酯化

  摘要：

  旋光性叔胺路易斯碱与不饱和酰氯反应，生成手性α，β-不饱和酰基铵盐。这些中间体参与催化，对映选择性，三组分过程，通过迈克尔-迈克尔-醛醇-β-内酯化作用传递双环和三环β-内酯。在一次操作中，所描述的多组分有机级联过程通过产生四个新键，两个环和最多四个连续的立体中心，形成复杂的双环和三环β-内酯。在外消旋系列中，使用4-吡咯烷二吡啶作为路易斯碱可实现22-75％的收率。在采用异硫脲催化剂的对映选择性系列中，最初形成的外消旋迈克尔加合物的动力学拆分似乎有效，提供了高达94：6 er的定量产率（基于最大含量的50％）为46％。经过优化（推测产率为61％，94：6 er）后，通过推测的可逆Michael获得了1d。

  DOI：

  10.1021/acs.joc.7b02543

文献信息

• [EN] FUSED POLYCYCLIC 2-PYRIDINONE ANTIBACTERIAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIBACTÉRIENS DE 2-PYRIDINONE POLYCYCLIQUE
  申请人：PTC THERAPEUTICS INC

  公开号：WO2016109706A1

  公开（公告）日：2016-07-07

  The present description relates to fused polycyclic 2-pyridinone compounds and forms and pharmaceutical compositions thereof and methods of using such compounds, forms or compositions thereof for treating or ameliorating a wild-type or drug-resistant form of N. gonorrhoeae or N. meningitides. A compound of Formula (la), Formula (lb) or Formula (Ic), or a form thereof, wherein the dashed lines represent one or more double bonds optionally present where allowed by available valences.

  本描述涉及融合的多环2-吡啶酮化合物及其形式和药物组合物，以及使用这些化合物、形式或组合物治疗或改善N. gonorrhoeae或N. meningitides的野生型或耐药型的方法。其中，化合物的化学式为（la）、（lb）或（Ic），或其形式，其中虚线代表一个或多个双键，根据可用的价键允许的情况下可选择地存在。
• Carbenoid Pathways in Copper-Catalyzed Intramolecular Cyclopropanations of Phenyliodonium Ylides
  作者：Paul Müller、Christelle Boléa

  DOI：10.1002/1522-2675(20010516)84:5<1093::aid-hlca1093>3.0.co;2-t

  日期：2001.5.16

  cyclopropanation of allyl diazomalonates and the corresponding phenyliodonium ylides was investigated with a series of chiral, non-racemic ligands. The reaction of 6b in the presence of the bis[dihydrooxazole] ligand Xa in refluxing 1,2-dichloroethane proceeded to 8b with an enantiomer excess (ee) of up to 72% under optimized conditions. In contrast, 8b resulting from reaction of ylide 7b with the same

  用一系列手性非外消旋配体研究了铜催化的重氮丙二酸烯丙酯分子内环丙烷化反应和相应的苯基碘叶立德的对映选择性。6b 在双[二氢恶唑] 配体 Xa 存在下在回流的 1,2-二氯乙烷中的反应进行到 8b，在优化条件下对映异构体过量 (ee) 高达 72%。相比之下，由叶立德 7b 与相同配体反应产生的 8b，但在 0°的 CH2Cl2 中，ee 仅为 30%。然而，与其他配体相比，重氮丙二酸酯 6b 的对映选择性低于内立德 7b。乙酰乙酸衍生的苯基碘鎓叶立德 15b 的分子内环丙烷化得到具有 68% ee 和配体 Xa 的 16b，但相应的重氮化合物在暴露于手性铜催化剂时不反应。叶立德 7 和 15 的 Cu 催化反应中不对称诱导的观察与类卡宾机制一致；然而，在重氮丙二酸 6b 和叶立德 7b 之间观察到的对映选择性的差异表明，在铜的配位范围之外，环丙烷化的竞争性非选择性途径。
• Dipeptidomimetic Ketomethylene Isosteres as Pro-moieties for Drug Transport via the Human Intestinal Di-/Tripeptide Transporter hPEPT1:  Design, Synthesis, Stability, and Biological Investigations
  作者：Jon Våbenø、Carsten Uhd Nielsen、Truls Ingebrigtsen、Tore Lejon、Bente Steffansen、Kristina Luthman

  DOI：10.1021/jm040780c

  日期：2004.9.1

  Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity for the di-/tripeptide transporter hPEPT1, and the transepithelial transport properties of the model prodrugs were investigated. ValPsi[COCH2]-Asp(OBn) was the compound with highest chemical stability in buffers at pH 6.0 and 7.4, with half-lives of 190 and 43 h, respectively. All five compounds showed high affinity for hPEPT1 (K-i values < 1 mM), and PhePsi[COCH2]Asp(OBn) and ValPsi[COCH2]Asp(OBn) had the highest affinities with K-i values of 68 and 19 muM, respectively. Am hPEPT1-mediated transport component was demonstrated for the transepithelial transport of three compounds, a finding that was corroborated by hPEPT1-mediated intracellular uptake. The results indicate that the stabilized Phe-Asp and Val-Asp derivatives are promising pro-moieties in a prodrug approach targeting hPEPT1.
• Multicomponent, Enantioselective Michael–Michael-Aldol-β-Lactonizations Delivering Complex β-Lactones
  作者：Khoi N. Van、Daniel Romo

  DOI：10.1021/acs.joc.7b02543

  日期：2018.1.19

  Optically active, tertiary amine Lewis bases react with unsaturated acid chlorides to deliver chiral, α,β-unsaturated acylammonium salts. These intermediates participate in a catalytic, enantioselective, three-component process delivering bi- and tricyclic β-lactones through a Michael–Michael-aldol-β-lactonization. In a single operation, the described multicomponent, organocascade process forms complex

  旋光性叔胺路易斯碱与不饱和酰氯反应，生成手性α，β-不饱和酰基铵盐。这些中间体参与催化，对映选择性，三组分过程，通过迈克尔-迈克尔-醛醇-β-内酯化作用传递双环和三环β-内酯。在一次操作中，所描述的多组分有机级联过程通过产生四个新键，两个环和最多四个连续的立体中心，形成复杂的双环和三环β-内酯。在外消旋系列中，使用4-吡咯烷二吡啶作为路易斯碱可实现22-75％的收率。在采用异硫脲催化剂的对映选择性系列中，最初形成的外消旋迈克尔加合物的动力学拆分似乎有效，提供了高达94：6 er的定量产率（基于最大含量的50％）为46％。经过优化（推测产率为61％，94：6 er）后，通过推测的可逆Michael获得了1d。