(+/-)-trans-1-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylic acid methyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (+/-)-trans-1-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylic acid methyl ester
• 英文别名: methyl (2S,3S)-1-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylate
• 化学式: C₁₉H₁₉NO₃
• 分子量: 309.365
• InChiKey: VIVJJEVKDNBJHY-FUHWJXTLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 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：

  (+/-)-trans-1-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylic acid methyl ester 在 钾硼氢 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以78%的产率得到(+/-)-1-benzyl-4-(hydroxymethyl)-5-phenylpyrrolidin-2-one
  参考文献：
  名称：

  Burdzhiev, Nikola T.; Stanoeva, Elena R., Zeitschrift fur Naturforschung, B: Chemical Sciences, 2008, vol. 63, # 3, p. 313 - 320

  摘要：

  DOI：
• 作为产物：
  描述：

  4-(benzylamino)-4-oxo-2-(p-tolylthio)butanoic acid 在 Raney nickel 2800 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 、 甲苯 为溶剂， 反应 26.0h， 生成 (+/-)-trans-1-benzyl-5-oxo-2-phenylpyrrolidine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  通过一锅四组分反应非对映选择性合成γ-内酰胺。

  摘要：

  已发现胺，马来酸酐，醛和硫醇之间的一种新的一锅四组分反应（4CR）可以形成具有高非对映选择性的四取代和五取代的γ-内酰胺。每个成分都是独立可变的，并以等效的化学计量法使用，仅产生水作为副产物。

  DOI：

  10.1021/ol701911u

文献信息

• From Nature to Synthetic Compounds: Novel 1(N),2,3 Trisubstituted-5-oxopyrrolidines Targeting Multiple Myeloma Cells
  作者：Roberta Listro、Alessio Malacrida、Francesca Alessandra Ambrosio、Giacomo Rossino、Marcello Di Giacomo、Valeria Cavalloro、Martina Garbagnoli、Pasquale Linciano、Daniela Rossi、Guido Cavaletti、Giosuè Costa、Stefano Alcaro、Mariarosaria Miloso、Simona Collina

  DOI：10.3390/ijms232113061

  日期：——

  The insurgence of drug resistance in treating Multiple Myeloma (MM) still represents a major hamper in finding effective treatments, although over the past decades new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have been discovered. Recently, our research team, within a Nature-Aided Drug Discovery project, isolated from Hibiscus Sabdariffa L. calyces the secondary metabolite called Hib-ester which possesses antiproliferative properties against human multiple myeloma RPMI 8226 cells, reduces migration and cell invasion and inhibits proteasome without neurotoxic effects. In the present study, we explored the chemical spaces of the hit compound Hib-ester. We explored the structure-activity relationships (SAR), and we optimized the scaffold through sequentially modifying Hib-ester subunits. Compound screening was performed based on cytotoxicity against the RPMI 8226 cells to assess the potential efficacy toward human MM. The ability of the most effective molecules to inhibit the proteasome was evaluated and the binding mode of the most promising compounds in the proteasome chymotrypsin binding pocket was deciphered through molecular modeling simulations. Compounds 13 and 14 are more potent than Hib-ester, demonstrating that our strategy was suitable for the identification of a novel chemotype for developing possible drug candidates and hopefully widening the drug armamentarium against MM.

  过去几十年来，虽然蛋白酶体抑制剂和免疫调节药物等新药不断被发现，但治疗多发性骨髓瘤（MM）的抗药性问题仍然是找到有效治疗方法的主要障碍。最近，我们的研究团队在一个自然辅助药物发现项目中，从木槿萼片中分离出了一种名为 Hib-ester 的次级代谢产物，它具有抗人多发性骨髓瘤 RPMI 8226 细胞增殖的特性，能减少细胞迁移和侵袭，并能抑制蛋白酶体，且无神经毒性作用。在本研究中，我们探索了命中化合物 Hib-ester 的化学空间。我们探索了结构-活性关系（SAR），并通过连续修饰 Hib-ester 亚基优化了支架。根据对 RPMI 8226 细胞的细胞毒性进行了化合物筛选，以评估对人类 MM 的潜在疗效。评估了最有效分子抑制蛋白酶体的能力，并通过分子建模模拟破译了最有希望的化合物在蛋白酶体糜蛋白酶结合袋中的结合模式。化合物 13 和 14 比 Hib-ester 更有效，这表明我们的策略适用于鉴定新的化学类型，以开发可能的候选药物，并有望扩大抗 MM 的药物范围。
• Diastereoselective Synthesis of γ- and δ-Lactams from Imines and Sulfone-Substituted Anhydrides
  作者：Nohemy A. Sorto、Michael J. Di Maso、Manuel A. Muñoz、Ryan J. Dougherty、James C. Fettinger、Jared T. Shaw

  DOI：10.1021/jo500050n

  日期：2014.3.21

  Sulfone-substituted gamma- and delta-lactams have been prepared in a single step with high diastereoselectivity. Sulfonylglutaric anhydrides produce intermediates that readily decarboxylate to provide delta-lactams with high diastereoselectivity. Substituents at the 3- or 4-position of the glutaric anhydride induce high levels of stereocontrol. Sulfonylsuccinic anhydrides produce intermediate carboxylic acids that can be trapped as methyl esters or allowed to decarboxylate under mild conditions. This method has been applied to a short synthesis of the pyrrolizidine alkaloid (+/-)-isoretronecanol.
• Copper-Catalyzed Three-Component Tandem Reactions for the Synthesis of β-Carboalkoxy-γ-lactams
  作者：Zhengning Li、Yunyun Feng、Zengchang Li、Lan Jiang

  DOI：10.1055/s-0034-1379482

  日期：——

  beta-Carboalkoxy--lactams were synthesized in high yields via copper-catalyzed three-component reactions of ,-unsaturated dicarboxylate esters, aldimines, and a silane. The reaction proceeds in a tandem manner via conjugate reduction, Mannich reaction, and a subsequent lactamization. The method is attractive with regard to the flexible combination of easily available reactants, the mild conditions, and the high yields. It provides a concise synthetic route to functionalized lactams with a -ester group.