Amidoglycosylation Reactions of Glycal Metallanitrenes

糖金属氮烯的酰胺糖基化反应

• 批准号: 7629238
• 负责人: CHRISTIAN M. ROJAS
• 金额: $ 0.94万
• 依托单位: BARNARD COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7629238
• 关键词: Acids; Affect; Alkenes; Amino Sugars; Arts; Aziridines; Biological; Carbamates; Chemistry; Chemistry, Other; Chitinase; Complex; Coupling; Development; Disaccharides; Electrons; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Ethers; Ethyl Ether; Face; Glucal; Goals; Investigation; Iodine; Link; Membrane Glycoproteins; Metals; Methodology; Methods; Modeling; Molecular; Molecular Conformation; Nitrogen; Object Attachment; Organic Chemicals; Organic Chemistry; Outcome; Oxidants; Polymers; Preparation; Process; Range; Reaction; Research; Rhodium; Role playing therapy; Route; Students; System; Technology; Testing; Woman; abstracting; allosamidin; allosamine; amidation; analog; aziridine; base; carboxylate; career; catalyst; chemical synthesis; college; design; enol; forging; glycosylation; improved; inhibitor/antagonist; insight; iodosobenzene; metal complex; method development; nitrene; oxidation; programs; research and development; stereochemistry; sugar

Project Summary/Abstract: The goals of the proposed research are the development, mechanistic description, and application of new methodology for the synthesis of 2-amino sugars, crucial molecular components and precursors in biological systems, including structural polymers, enzyme inhibitors, and cell-surface glycoproteins. The synthetic approach uses glycal 3-carbamates as starting materials and proceeds through a tandem alkene amidation- glycosylation sequence-amidoglycosylation-to introduce nitrogen at C2 of the sugar framework and to establish an anomeric linkage to a nucleophilic reaction partner, the glycosyl acceptor. Iodosobenzene carries out this overall oxidation, in a process best catalyzed by dirhodium(II) carboxylates and apparently involving a rhodium-complexed acyl nitrene intermediate. The amidation step is intramolecular, forging the C2-N bond on the more hindered glycal face, and, ideally, glycosylation should occur stereospecifically, anti to the newly incorporated nitrogen substituent. While certain glycal 3-carbamates react with efficiency and high anomeric stereoselectivity, other substrates with potentially high synthetic value provide substantial amounts of C3-oxidized dihydropyranone byproducts and low stereocontrol in the glycosylation step. Using the mechanistic hypotheses that (1) both amidoglycosylation and C3 oxidation occur via a common metallanitrene intermediate and (2) stereoselective glycosylation requires neighboring-group participation from the C2 nitrogen, probably by way of a glycosyl aziridine, this application outlines how controlling the conformation of the glycal 3-carbamate framework will enable both high chemo- and stereoselectivity in the amidoglycosylation reactions. Other proposed investigations will further illuminate mechanistic details of the reactions, providing crucial information for improving and increasing the utility and scope of amidoglycosylation for the preparation of amino sugars. With input from both the method development and mechanistic study components of the proposed project, this application outlines the completion of a synthesis of the disaccharide portion of the potent chitinase inhibitor allosamidin. Iterative application of the amidoglycosylation technology will enable streamlined preparation of an allosamidin disaccharide module readily amenable for analogue synthesis. To be conducted at Barnard College, an undergraduate liberal arts college for women, the project will provide students with numerous opportunities in organic chemical synthesis, helping to attract and propel them into careers in chemistry and other health-related professions.

项目摘要/摘要： 拟议研究的目标是新的开发，机理描述和应用 生物学中2-氨基糖，关键分子成分和前体合成的方法 系统，包括结构聚合物，酶抑制剂和细胞表面糖蛋白。合成 方法使用甘氨酸3-氨基甲酸酯作为起始材料，并通过串联烯烃胺进行进行 - 糖基化序列 - 氨基糖基化来在糖框架的C2上引入氮，然后 与亲核反应伴侣，糖基受体建立异构键。碘苯苯携带 消除这种总体氧化，在最佳的过程中，羧基（II）羧酸盐催化，显然涉及 若ius子复合的丙烯中间体。脑分子内的趋势步骤，在上锻造C2-N键 甘油的面部较受阻，理想情况下，糖基化应立体特定于新近的糖基化。 掺入氮取代基。虽然某些甘氨酸3-氨基甲酸酯效率和高异常反应 立体选择性，其他具有高合成价值的底物提供了大量 糖基化步骤中的C3氧化二氢吡喃酮副产物和低立体控制。使用 机械假设是（1）通过常见的金属苯乙烯出现酰胺基化和C3氧化 中间和（2）立体选择性糖基化需要C2的相邻参与 氮，可能是通过糖基苯胺，该应用概述了如何控制的构象 甘氨酸3-氨基酯框架将在胺化学中同时实现高化学和立体选择性 反应。其他提议的调查将进一步阐明反应的机理细节，提供 提高和增加酰胺基化的效用和范围的关键信息 氨基糖。通过方法开发和机械研究组成部分的输入 拟议的项目，本应用程序概述了完成二糖的合成部分 有效的几丁质抑制剂同胺。胺化技术的迭代应用将启用 同种胺二糖模块的精简制备容易适合模拟合成。到 该项目将在Barnard College（一所本科生的文科学院）进行 有许多有机化学合成的机会的学生，有助于吸引和推动他们进入 化学和其他与健康有关的职业。

项目成果

Dihydropyranone formation by ipso C-H activation in a glucal 3-carbamate-derived rhodium acyl nitrenoid.

在葡萄糖 3-氨基甲酸酯衍生的铑酰基氮烯化合物中通过 ipso C-H 活化形成二氢吡喃酮。

• DOI: 10.1021/jo101599q
• 发表时间: 2011
• 期刊: The Journal of organic chemistry
• 作者: Hurlocker,Brisa;Abascal,NadiaC;Repka,LindsayM;Santizo-Deleon,Elsy;Smenton,AbigailL;Baranov,Victoria;Gupta,Ritu;Bernard,SarahE;Chowdhury,Shenjuti;Rojas,ChristianM
• 通讯作者: Rojas,ChristianM

Protecting group and solvent control of stereo- and chemoselectivity in glucal 3-carbamate amidoglycosylation.

葡萄糖3-氨基甲酸酯酰胺糖基化中立体选择性和化学选择性的保护基团和溶剂控制。

• DOI: 10.1021/ol900126q
• 发表时间: 2009
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Gupta,Ritu;Sogi,KimberlyM;Bernard,SarahE;Decatur,JohnD;Rojas,ChristianM
• 通讯作者: Rojas,ChristianM