(2R,4S)-benzyl 4-allyl-4-methyl-5-oxo-2-phenyloxazolidine-3-carboxylate | 1445137-76-7

• 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: (2R,4S)-benzyl 4-allyl-4-methyl-5-oxo-2-phenyloxazolidine-3-carboxylate
• 英文别名: benzyl (2R,4S)-4-methyl-5-oxo-2-phenyl-4-prop-2-enyl-1,3-oxazolidine-3-carboxylate
• CAS: 1445137-76-7
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: NSRWBOVKKMAQPX-NQIIRXRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,4S)-benzyl 4-allyl-4-methyl-5-oxo-2-phenyloxazolidine-3-carboxylate 在 9-硼双环[3.3.1]壬烷 作用下， 生成 (2S)-5-amino-2-methyl-2-(phenylmethoxycarbonylamino)pentanoic acid
  参考文献：
  名称：

  Engineering strategy to improve peptide analogs: from structure-based computational design to tumor homing

  摘要：

  CREKA（Cys-Arg-Glu-Lys-Ala）能与肿瘤血管中的纤维蛋白和纤维蛋白相关凝血浆蛋白结合（Simberg 等人，发表于 Proc Natl Acad Sci USA 104:932-936, 2007），具有更强的抑制肿瘤生长的能力。我们采用模拟退火和分子动力学相结合的方法进行了计算机建模，以设计有针对性的替代物，从而提高 CREKA 生物活性构象的稳定性。由于这种构象呈现出类似口袋的形状，Arg、Glu 和 Lys 的带电基团指向外侧，因此我们选择了 Arg、Glu 和 Lys 的非蛋白源氨基酸 α-甲基和 N-甲基衍生物，并对其进行了合理设计，将其加入到 CREKA 类似物中。根据建模预测，不同 CREKA 类似物的生物活性构象的稳定性与肿瘤荧光结果相吻合，肿瘤蓄积量随着稳定性的增加而增加。在此，我们报告了建模、合成过程以及用于测试类似物疗效和实用性的新生物检测方法。我们的研究结果综合展示了基于多学科合作的研究如何汇聚在一起，并带来有用的生物医学进步。

  DOI：

  10.1007/s10822-012-9623-5
• 作为产物：
  描述：

  N-benzyloxycarbonyl-D-alanine 在 氯化亚砜 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 为溶剂， 反应 6.17h， 生成 (2R,4S)-benzyl 4-allyl-4-methyl-5-oxo-2-phenyloxazolidine-3-carboxylate
  参考文献：
  名称：

  Design of Cell-Permeable Stapled Peptides as HIV-1 Integrase Inhibitors

  摘要：

  HIV-1 integrase (IN) catalyzes the integration of viral DNA into the host genome involving several interactions with the viral and cellular proteins. We have previously identified peptide IN inhibitors derived from the a-helical regions along the dimeric interface of HIV-1 IN. Herein, we show that appropriate hydrocarbon stapling of these peptides to stabilize their., helical structure remarkably improves the cell permeability, thus allowing inhibition of the HIV-1 replication in cell culture. Furthermore, the stabilized peptides inhibit the interaction of IN with the cellular cofactor LEDGF/p75. Cellular uptake of the stapled peptide was confirmed in four different cell lines using a fluorescein-labeled analogue. Given their enhanced potency and cell permeability, these stapled peptides can serve as not only lead IN inhibitors but also prototypical biochemical probes or "nanoneedles" for the elucidation of HIV-1 IN dimerization and host cofactor interactions within their native cellular environment.

  DOI：

  10.1021/jm4006516

文献信息

• Synthesis of 4-hydroxy-2-methylproline derivatives via pyrrolidine ring assembly: chromatographic resolution and diastereoselective synthesis approaches
  作者：Vinay Shankar Tiwari、Raghavendra Murugula、Shyam Raj Yadav、Wahajul Haq

  DOI：10.1016/j.tetasy.2016.07.001

  日期：2016.10

  4-Hydroxy-2-methylproline diastereomers are successfully prepared without the use of an external chiral auxiliary. Dihydroxylation of the key intermediate 2 resulted in lactone 4 as a mixture of diastereomers in good yield. Mesylation, hydrogenation and concomitant intramolecular cyclization of 4 led to the formation of both (2R,4R)- and (2R,4S)-4-hydroxy-2-methylprolines as a mixture of diastereomers. Appropriate protection followed by chromatographic separation resulted in isolation of both cis- and trans-diastereomers in enantiomerically pure form and in equal quantity. In subsequent experiments, the synthesis of the more challenging diastereomers (2R,4R)- and (2S,4S)-4-hydroxy-2-methylproline was achieved by diastereoselective iodolactonization of (R)- or (S)-allylalanine obtained after hydrolysis of intermediate 2, followed by pyrrolidine ring closer under mild alkaline conditions. After selective protection and deprotection, Fmoc-(2R,4R)-alpha-Me-Hyp(Bu-t)-OH 14, a building block suitable for solid phase peptide synthesis was obtained. (C) 2016 Elsevier Ltd. All rights reserved.