APPROACHES TO MACROLIDE & IONOPHORE ANTIBIOTIC SYNTHESIS

这项提议的主要目标是实施新的 亚基的立体控制合成方法学 极其重要的大环内酯类抗生素泰乐菌素和广谱霉素B 在开发这些路线的同时，我们还打算生产 离子载体抗生素，特别是离子霉素的亚基，我们建议 目的：合成石松生物碱Luciduline。这些目标是被选中的 为了说明我们开发的新方法的适用性 6-和6-取代基立体专一性引入实验室 利用强引导性的七元碳环 连接到环上的过渡金属部分的影响。这种方法 承诺足够灵活，以允许合成类似物 天然产物，从而对疾病有潜在的贡献 控制力。 泰乐菌素和玛格那霉素B的应用探讨 全新的合成原理。因此，键5的合成， 7-二取代环庚二烯是一种立体专一性的方式，通过 环庚二烯铁络合物的手段，代表完全 史无前例的立体专门化功能的方法 七人环。产品环庚二烯的后续精制 将使用区域和立体特异性内酯化方法进行研究 我国相关环己二烯基乙酸的最新研究进展 实验室。 环庚二烯基铁络合物的使用也具有相当大的价值 为了制备天然产生的大环内酯类类似物，因为 取代基的性质有相当大的灵活性 从而给出了代换变化的方法 图案。~(13)C和~(13)H标记的放射性标记化合物的合成 化合物也可以实现，这些将对以下方面非常有用 作用方式和代谢的体外和体内研究。

The major objective of this proposal is the implementation of new methodology for stereocontrolled synthesis of subunits found in the exceedingly important macrolide antibiotics tylosin and magnamycin B. Alongside the development of these routes we also intend to produce subunits for ionophore antibiotics, in particular ionomycin, and we propose to synthesize the Lycopodium alkaloid luciduline. These targets are chosen to illustrate the applicability of new methodology developed in our laboratory for stereospecific introduction of substituents onto six- and seven-membered carbocyclic rings which utilizes the powerful directing effect of a transition metal moiety attached to the ring. This approach promises to be sufficiently flexible to allow the synthesis of analogs of the natural products, thereby making a potential contribution to disease control. The approach to tylosin and magnamycin B which is to be followed uses entirely new synthetic principles. Thus, synthesis of a key 5, 7-disubstituted cycloheptadiene is a stereospecific manner is effected by means of a cycloheptadiene iron complex, representing an entirely unprecedented method for the stereospecific functionalisation of the seven-membered ring. Subsequent elaboration of the product cycloheptadiene will be investigated using a regio- and stereospecific lactonisation method recently developed on related cyclohexadienylacetic acids in our laboratories. The use of cycloheptadienyl iron complexes is also of considerable value for preparation of analogs of the naturally occurring macrolides, since there is considerable flexibility concerning the nature of substituents which are introduced, thereby giving methods for variation of substitution pattern. Synthesis of radiolabeled, carbon 13- and deuterium-labeled compounds can also be accomplished, and these would be extremely useful for in vitro and in vivo studies of mode of action and metabolism.