Synthesis of 2-Aminoimidazole-Based Alkaloids

2-氨基咪唑类生物碱的合成

• 批准号: 6822866
• 负责人: DAVID A. HORNE
• 金额: $ 24.76万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6822866
• 关键词: Dinoflagellates; alkaloids; biomedical resource; biotechnology; biotherapeutic agent; chemical structure; chemical synthesis; guanidines; imidazole; marine toxins; method development; oxazolidone; pyrroles; saxitoxin; spirane

DESCRIPTION (provided by applicant): The plan of this investigation is twofold in nature. The overall objective is to develop concise and efficient syntheses of synthetically and technically challenging 2-aminoimidazole based sponge alkaloids known as the oroidin alkaloids. In particular, we plan to synthesize sceptrin (4), dibromoagelaspongin (6), ageliferin (7), palau'amine (9), agelastatin D (12), and axinellamine (14). Collectively, these and other structurally related metabolites possess a myriad of potent biological effects. An important goal within this research endeavor is the development and validation of a unifying chemical approach to this structurally novel class of natural products. The proposed methods and routes are essentially devoid of protecting groups and are guided by biogenetic considerations. The synthetic plan calls for methods development for transforming 2- aminoimidazoles into key intermediates for the synthesis of the naturally occurring compounds. The preparation of these intermediates and the facility of the ensuing molecular rearrangements would tend to support or disclaim the biogenetic hypothesis. Versatile and efficient syntheses of these metabolites would provide access to structurally modified or specifically labeled substrates for biomedical research. In addition, the methods developed in this area will be applied to synthesis of the red-tide toxins, saxitoxin, gonyautoxin I and gonyautoxin IV.

描述（由申请人提供）：本次调查的计划有两个性质。总体目标是开发简洁高效的合成方法，合成和技术上具有挑战性的2-氨基咪唑基海绵生物碱，即蛇柳苷生物碱。我们计划合成sceptrin(4)、dibromoagelaspongin(6)、agelifin(7)、palau'amine(9)、agelastatin D（12）和axinellamine（14）。总的来说，这些和其他结构相关的代谢物具有无数强有力的生物效应。这项研究的一个重要目标是开发和验证一种统一的化学方法来处理这种结构新颖的天然产物。拟议的方法和路线基本上没有保护群体，而是以生物遗传学考虑为指导。该合成计划要求开发将2-氨基咪唑转化为天然化合物合成的关键中间体的方法。这些中间体的制备和随后的分子重排的便利将倾向于支持或否认生物遗传学假说。这些代谢物的多功能和高效合成将为生物医学研究提供结构修饰或特异性标记的底物。此外，本领域所建立的方法将应用于红潮毒素、蛤蚌毒素、gonyautoxin I和gonyautoxin IV的合成。