Synthesis of 2-Aminoimidazole-Based Alkaloids

描述(申请人提供)：本次调查计划具有双重性质。总体目标是开发合成和技术上具有挑战性的2-氨基咪唑类海绵生物碱的简明和有效的合成方法，被称为oroidin生物碱。特别是，我们计划合成羊栖菜苷(4)、二溴琼脂糖苷(6)、皂苷(7)、帕劳胺(9)、琼脂糖苷D(12)和木犀草胺(14)。总体而言，这些和其他结构相关的代谢物具有无数强大的生物效应。这项研究工作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类结构新颖的天然产品。建议的方法和路线基本上没有保护基团，并以生物遗传考虑为指导。合成计划要求开发将2-氨基咪唑转化为合成天然化合物的关键中间体的方法。这些中间体的制备和随之而来的分子重排的便利将倾向于支持或否定生物发生假说。这些代谢物的多用途和高效合成将为生物医学研究提供结构修饰或特殊标记的底物。此外，在这方面开发的方法将应用于赤潮毒素、岩藻毒素I和裸藻毒素IV的合成。

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.