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方法的开发、机制描述和应用 2-氨基糖、生物中关键分子成分和前体的合成方法 系统，包括结构聚合物、酶抑制剂和细胞表面糖蛋白。合成的 该方法使用糖醛3-氨基甲酸酯作为起始原料，并通过串联烯烃酰胺化进行- 糖基化序列-酰胺糖基化-在糖框架的C2处引入氮并 与亲核反应伙伴（糖基受体）建立异头连接。碘代苯携带 整个氧化过程最好由羧酸二铑(II)催化，并且显然涉及 铑络合酰基氮烯中间体。酰胺化步骤是分子内的，在分子上形成 C2-N 键 受阻糖基面越多，并且理想情况下，糖基化应该立体特异性地发生，与新的糖基化相反 并入氮取代基。虽然某些糖醛 3-氨基甲酸酯的反应效率高且异头性高 立体选择性，具有潜在高合成价值的其他底物提供了大量的 C3-氧化二氢吡喃酮副产物和糖基化步骤中的低立体控制。使用 机制假设 (1) 酰胺糖基化和 C3 氧化均通过共同的金属氮烯发生 中间体和 (2) 立体选择性糖基化需要 C2 邻近基团的参与 氮，可能通过糖基氮丙啶的方式，该应用概述了如何控制 糖基 3-氨基甲酸酯框架将使酰胺糖基化具有高化学选择性和立体选择性 反应。其他拟议的研究将进一步阐明反应的机制细节，提供 改进和增加酰胺糖基化制剂的效用和范围的重要信息 氨基糖。通过方法开发和机制研究部分的输入 拟议的项目，该申请概述了二糖部分的合成的完成 有效的几丁质酶抑制剂异糖脒。酰胺糖基化技术的迭代应用将使 易于进行类似物合成的别糖脒二糖模块的简化制备。到 该项目将在巴纳德学院（Barnard College）进行，这是一所女子本科文理学院，该项目将提供 学生在有机化学合成方面有很多机会，有助于吸引和推动他们进入 化学和其他健康相关职业的职业。

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