A General Synthetic Route to Glycosidase Inhibitors

糖苷酶抑制剂的通用合成路线

• 批准号: 7097157
• 负责人: AARON APONICK
• 金额: $ 3.26万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-11-16 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7097157
• 关键词: aminoalcohol; chemical synthesis; enzyme inhibitors; epoxides; glycosidases; nitrogen; palladium; postdoctoral investigator; stereoisomer; technology /technique development

DESCRIPTION (provided by applicant): The goal of the research outlined in this proposal is to investigate the scope of the palladium catalyzed dynamic kinetic asymmetric transformation (DYKAT) of racemic diene monoepoxides to enantiomerically pure 1,2-aminoalcohols and to apply this methodology to the synthesis of the natural products 2,5-dihydroxymethyl-3,4-dihydroxy- pyrrolidine, 1-deoxynojiromycin, swainsonine, 1-epi-alexine, and gualamycin, which are potent glycosidase inhibitors and represent four of the five general structural classes of these compounds. The reaction will be investigated by expanding the list of nitrogen nucleophiles and epoxides that can be used. In optimizing the reactions, advanced intermediates necessary for straightforward transformation into these inhibitors will be generated. Efficient enantioselective chemical syntheses by flexible routes using the proposed DYKAT methodology will provide a general synthetic strategy for the synthesis of a multitude of structurally similar alkaloids, which have been identified as potential pharmaceuticals in the therapeutic areas of cancer, diabetes, obesity, and anti-virals.

描述（由申请人提供）：该提案中概述的研究的目的是研究钯催化的动态动态动力学不对称转化（DYKAT）的二烯基二氧化物的动态动力学不对称转化（Dykat），以对映体纯纯的1,2-氨基醇，并将此方法应用于自然产品的合成。 2,5-二羟基甲基-3,4-二羟基 - 吡咯烷，1-脱氧诺二摩霉素，瑞士氨氨酸，1-甲氧霉素和二霉素，它们是有效的糖苷酶抑制剂，代表了这些化合物的五个常规结构类别中的四个。该反应将通过扩大可以使用的氮核和环氧化物的清单来研究。在优化反应时，将产生直接转化为这些抑制剂所需的高级中间体。使用拟议的Dykat方法学的柔性途径有效的对映选择性化学合成将为合成多种结构相似的生物碱的合成提供一般的合成策略，这些生物碱已被鉴定为癌症，糖尿病，肥胖症和抗毒理学的治疗区域中潜在的药物。