SYNTHESES OF BIOLOGICALLY ACTIVE MARINE ALKALOIDS

描述：此修订后的应用程序的计划是开发新的 综合方法论和战略构建2- 以氨基咪唑和胍为基础的海洋天然产物 重要的生物活动。据指出，值得注意的是 代表化合物包括三环海洋色素黄黄嘌呤(1) 和(2)，C11N5家族的Oroidin生物碱(3-7)，二聚Oroidin 生物碱(8-10)和赤潮毒素--麻黄毒素(11)和 弓形虫毒素(12)。据报道，总的来说，这些和其他 结构上相关的化合物具有很强的药理作用 包括抗病毒、抗白血病、抗肿瘤、抗5-羟色胺能 以及α-肾上腺素能受体和离子通道阻断活动以及 此外，一种罕见的ATPase刺激活性的例子 肌球蛋白和肌动球蛋白最近被观察到。校长 研究人员指出，尽管每类代谢物都是 然而，它们在结构上是独一无二的，它们代表了结构的集合 它们的多样性与它们共享的丰富化学物质有关 很普通。拟议的研究将重点放在开发方法和 涉及氧化和非氧化转化的战略 对合成具有普遍适用性的2-氨基咪唑类化合物 上述杂环。需要特别指出的是， 这些方法在建议的双环合成中进行了描述。 冬凌草素生物碱，膜片碱(6)，二聚冬凌草素生物碱， Ageliferin(8)(R=H)和sceptrin(9)以及有效的神经毒素 黑曲霉毒素(11)和刚尾藻毒素(12)。首席调查员 表示建议的方法和路线基本上是空的。 并基于生物遗传考虑。他 建议研究计划的一个整体特征是 证实可能的生物合成途径。有消息称， 综合计划要求开发方法将2- 将氨基咪唑转化为合成天然产物的关键中间体 生成的化合物和这些中间体的制备以及 随之而来的分子重排的便利性往往会 支持或否定生物发生假说。有人建议， 这些代谢物的多用途和高效合成将提供 获得结构修饰的或特别标记的衬底 生物医学研究。

DESCRIPTION: The plan of this revised application is to develop new synthetic methodologies and strategies for the construction of 2- aminoimidazole- and guanidine-based marine natural products possessing important biological activities. It is indicated that notable representatives include the tricyclic marine pigments zoanthoxanthins (1) and (2), the C11N5 family of oroidin alkaloids (3-7), dimeric oroidin alkaloids (8-10) and the red-tide toxins, saxitoxin (11) and gonyautoxins (12). It is reported that collectively, these and other structurally related compounds possess potent pharmacological properties that include antiviral, antileukemic, antineoplastic, antiserotonergic as well as alpha-adrenoceptor and ion-channel blocking activities and that in addition, a rare example of ATPase stimulating activities of myosin and actomyosin has recently been observed. The principal investigator notes that although each class of metabolites is structurally unique, they represent, however, a collection of structures whose diversity is related by the rich chemistry that they share in common. The proposed research is to focus on developing methodologies and strategies that involve oxidative and non-oxidative transformations of 2-aminoimidazoles that will have general applicability to synthesis of the above heterocycles. It is noted that in particular, the utility of these methods is delineated in the proposed synthesis of the bicyclic oroidin alkaloid hymenialdisines (6), the dimeric oroidin alkaloids, ageliferin (8) (R=H) and sceptrin (9), and the potent neurotoxins saxitoxin (11) and gonyautoxin (12). The principal investigator indicates that the proposed methods and routes are essentially devoid of protecting groups and are based on biogenetic considerations. He suggests that an integral feature of the research plan is a criterion for substantiating possible biosynthetic pathways. It is indicated that the synthetic plan calls for the development of methods for transforming 2- aminoimidazole into key intermediates for the synthesis of the naturally occurring compounds and that the preparation of these intermediates and the facility of the ensuing molecular rearrangements would tend to support or disclaim the biogenetic hypothesis. It is suggested that versatile and efficient syntheses of these metabolites would provide access to structurally modified or specifically labeled substrates for biomedical research.