(4S)-4-isopropyl-3-(4'-methylvaleryl)-2-oxazolidinone | 134806-81-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4S)-4-isopropyl-3-(4'-methylvaleryl)-2-oxazolidinone
• 英文别名: (S)-4-isopropyl-3-(4-methylpentanoyl)oxazolidin-2-one；(4S)-3-(4-Methylpentanoyl)-4-(2-propyl)oxazolidine-2-one；(4S)-3-(4-methylpentanoyl)-4-propan-2-yl-1,3-oxazolidin-2-one
• CAS: 134806-81-8
• 化学式: C₁₂H₂₁NO₃
• 分子量: 227.304
• InChiKey: VGMWZVMXAAKMKC-SNVBAGLBSA-N

物化性质

• 沸点：
  338.8±11.0 °C(Predicted)
• 密度：
  1.047±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S)-4-isopropyl-3-(4'-methylvaleryl)-2-oxazolidinone 在 lithium hydroxide 、 TEA 、 双氧水 、 四氯化钛 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2R)-2-(benzamidomethyl)-4-methylpentanoic acid
  参考文献：
  名称：

  β-肽作为催化剂：聚-β-亮氨酸作为烯酮的Juli-Colonna不对称环氧化的催化剂。

  摘要：

  聚-β-亮氨酸已被评估为朱尼-科隆娜烯不对称环氧化的催化剂。发现β3-异构体是查尔酮（70％ee）和某些类似物环氧化的有效催化剂。

  DOI：

  10.1039/b106368p
• 作为产物：
  描述：

  L-缬氨醇 在 正丁基锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 生成 (4S)-4-isopropyl-3-(4'-methylvaleryl)-2-oxazolidinone
  参考文献：
  名称：

  Progress towards the total synthesis of callipeltin A. Asymmetric synthesis of (2 R ,3 R ,4 S )-3-hydroxy-2,4,6-trimethylheptanoic acid

  摘要：

  A silyl derivative of (2R,3R,4S)-3-hydroxy-2,4,6-trimethylheptanoic acid, a moiety present in the cyclic depsipeptide callipeltin A, was successfully synthesized from L-valine in nine steps using the Heathcock variant of the Evans aldol reaction. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(02)00045-9

文献信息

• Evaluation of transition-state mimics in a superior BACE1 cleavage sequence as peptide-mimetic BACE1 inhibitors
  作者：Yasunao Hattori、Kazuya Kobayashi、Ayaka Deguchi、Yukie Nohara、Tomomi Akiyama、Kenta Teruya、Akira Sanjoh、Atsushi Nakagawa、Eiki Yamashita、Kenichi Akaji

  DOI：10.1016/j.bmc.2015.07.023

  日期：2015.9

  A superior substrate sequence for BACE1 containing transition-state mimics at the scissile site was evaluated as a protease inhibitor. Hydroxymethylcarbonyl (HMC) and hydroxyethylamine (HEA) isosteres were selected as the transition state mimics, and incorporated into the scissile site of the superior sequence covering the P4 to P1’ sites (Glu-Ile-Thi-Thi*Nva; *denotes the cleavage site). Isosteres

  易位处含有过渡态模拟物的BACE1的优良底物序列被评估为蛋白酶抑制剂。选择羟甲基羰基（HMC）和羟乙胺（HEA）等位基因作为过渡态模拟物，并将其并入覆盖P 4至P 1 '位的上位序列的易剪位点（Glu-Ile-Thi-Thi * Nva；*表示卵裂位点）。分别合成具有不同的羟基绝对构型的等排体，并评价构型的效果。每个等排异构体的羟基构型均显示出对抑制活性的显着影响。反对-易位部位取代基的构型在HMC型抑制剂中具有有效的抑制活性，而HEA型抑制剂的抗构型则没有抑制活性。基于重组BACE1与每种抑制剂的复合物的X射线晶体学分析进行结构评估，可深入了解蛋白质-配体之间的相互作用，尤其是在主要位点。
• Retroviral protease inhibiting compounds
  申请人：Abbott Laboratories

  公开号：US05142056A1

  公开（公告）日：1992-08-25

  A retroviral protease inhibiting compound of the formula A--X--B or a pharmaceutically acceptable salt, prodrug or ester thereof, wherein X is a linking group; A is (1) substituted amino, (2) substituted carbonyl, (3) functionalized imino, (4) functionalized alkyl, (5) functionalized acyl, (6) functionalized heterocyclic or (7) functionalized (heterocyclic)alkyl; and B is (1) substituted carbonyl independently defined as herein, (2) substituted amino independently defined as herein, (3) functionalized imino independently defined as herein, (4) functionalized alkyl independently defined as herein, (5) functionalized acyl independently defined as herein, (6) functionalized heterocyclic independently defined as herein or (7) functionalized (heterocyclic)alkyl independently defined as herein.

  一种抑制逆转录病毒蛋白酶的化合物，其化学式为A--X--B或其药用盐、前药或酯，其中X为连接基；A为（1）取代氨基，（2）取代羰基，（3）官能化亚胺基，（4）官能化烷基，（5）官能化酰基，（6）官能化杂环基或（7）官能化（杂环）烷基；B为（1）取代羰基，独立定义如本文所述，（2）取代氨基，独立定义如本文所述，（3）官能化亚胺基，独立定义如本文所述，（4）官能化烷基，独立定义如本文所述，（5）官能化酰基，独立定义如本文所述，（6）官能化杂环基，独立定义如本文所述或（7）官能化（杂环）烷基，独立定义如本文所述。
• Intermolecular Enolate Heterocoupling: Scope, Mechanism, and Application
  作者：Michael P. DeMartino、Ke Chen、Phil S. Baran

  DOI：10.1021/ja804159y

  日期：2008.8.27

  while iron(III)-based couplings appear to proceed through a non-templated heterodimerization. This work presents the most in-depth findings on the mechanism of oxidative enolate coupling to date. The scope of oxidative enolate heterocoupling is extensive (40 examples) and has been shown to be efficient even on a large scale (gram-scale or greater). Finally, the method has been applied to the total synthesis

  这篇完整的报告介绍了两种不同羰基物质的氧化分子间偶联的背景、发现和广泛的见解。该过程的优化最终形成了使用可溶性铜 (II) 或铁 (III) 盐作为氧化剂将酰胺、酰亚胺、酮和羟吲哚结合的可靠且可扩展的方案。广泛的机理研究表明，在铜 (II) 的情况下是金属螯合的单电子转移过程，而基于铁 (III) 的偶联似乎是通过非模板化的异二聚化进行的。这项工作提供了迄今为止对氧化烯醇偶联机制最深入的发现。氧化烯醇杂偶联的范围很广（40 个例子），并且已被证明即使在大规模（克级或更大）上也是有效的。最后，
• Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors
  作者：Ashvinikumar V. Gavai、Claude Quesnelle、Derek Norris、Wen-Ching Han、Patrice Gill、Weifang Shan、Aaron Balog、Ke Chen、Andrew Tebben、Richard Rampulla、Dauh-Rurng Wu、Yingru Zhang、Arvind Mathur、Ronald White、Anne Rose、Haiqing Wang、Zheng Yang、Asoka Ranasinghe、Celia D’Arienzo、Victor Guarino、Lan Xiao、Ching Su、Gerry Everlof、Vinod Arora、Ding Ren Shen、Mary Ellen Cvijic、Krista Menard、Mei-Li Wen、Jere Meredith、George Trainor、Louis J. Lombardo、Richard Olson、Phil S. Baran、John T. Hunt、Gregory D. Vite、Bruce S. Fischer、Richard A. Westhouse、Francis Y. Lee

  DOI：10.1021/acsmedchemlett.5b00001

  日期：2015.5.14

  series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of γ-secretase mediated signaling of Notch1/2/3/4 receptors. On the basis of its robust in vivo efficacy at tolerated doses in Notch driven leukemia and solid tumor xenograft models, 12 (BMS-906024) was selected as a candidate for clinical evaluation.

  一系列（2-oxo-1,4-苯并二氮杂-3-基）-琥珀酰胺的结构-活性关系确定了高效的γ-分泌酶抑制剂Notch1 / 2/3/4受体的抑制剂。基于在Notch驱动的白血病和实体瘤异种移植模型中以耐受剂量耐受的强大体内功效，选择12（BMS-906024）作为临床评估的候选药物。
• A Practical Approach for Enantio- and Diastereocontrol in the Synthesis of 2,3-Disubstituted Succinic Acid Esters: Synthesis of the pan-Notch Inhibitor BMS-906024
  作者：Claude Quesnelle、Patrice Gill、Soong-Hoon Kim、Libing Chen、Yufen Zhao、Brian Fink、Mark Saulnier、David Frennesson、Michael DeMartino、Phil Baran、Ashvinikumar Gavai

  DOI：10.1055/s-0035-1561636

  日期：——

  An oxidative intermolecular enolate heterocoupling reaction was employed for the synthesis of anti-2,3-disubstituted succinic acid mono- and differentially protected diesters. Tactical approaches to access all the diastereomers are discussed. The method was applied to the synthesis of a potent anticancer agent, BMS-906024.

  氧化分子间烯醇杂偶联反应用于合成抗 2,3-二取代琥珀酸单和差异保护的二酯。讨论了获取所有非对映异构体的战术方法。该方法用于合成一种有效的抗癌剂 BMS-906024。