SYNTHETIC STUDIES TOWARDS ADJACENTLY LINKED POLYETHER ANTIBIOTICS

相邻连接的聚醚残基包含几个以下结构： 天然产品的种类，具有广泛的重要性， 生物活动。 在这些化合物中， 抗生素，（抗球虫，心血管，抗艾滋病毒）和 acetogenins（抗肿瘤）。 该项目的长期目标是 开发了一种新的方法，用于制备高度 取代的聚醚，包括这些化合物的结构。 该合成方案基于一种新的形成2，5-二氯乙烷的方法。 二取代的四氢呋喃（THF）。 通过这个过程，A 单糖烯烃前体用卤离子处理， 在含水条件下，直接转化为高度取代的卤代- THF-醛。 反应是基于邻组参与 被单糖的环氧所取代 短期目标是 优化该反应的立体选择性。 的一个关键方面 该研究需要使用糖苷配基取代基作为 立体控制元件 为了制定一套规则， 预测立体选择性，单糖烯烃的反应， 其中糖苷配基的大小、电子性质和构型 会有所不同，会有所表现。 同时，激活或 糖苷配基结构对反应速率的钝化作用 会被注意到。 预测立体选择性和反应性的规则如下： 随后纳入一个新的计划， 相邻连接的聚醚，含有多达四个单元，从双- 糖烯烃前体。 由于它的碳水化合物来源， 该方法将特别适合于制备高度 羟基化聚醚衍生物。 此外，收敛性 该计划和各种天然糖的可用性 取代模式有利于高度结构“精细化 “调谐”，使得该方法对于药物类似物生产具有吸引力。

Adjacently linked polyether residues comprise the structure of several classes of natural products which have a wide range of important biological activities. Among these compounds are the ionophore antibiotics, (anticoccidial, cardiovascular, anti-HIV) and the acetogenins (antitumors). The long term goal of this project is the development of a novel methodology for the preparation of the highly substituted polyether that comprise the structure of these compounds. The synthetic plan is based on a new method for the formation of 2,5- disubstituted tetrahydrofurans (THF's). Via this procedure, a monosaccharide alkene precursor on treatment with halonium ion under aqueous conditions, is directly converted to a highly substituted halo- THF-aldehyde. The reaction is based on neighboring group participation by the ring oxygen of the monosaccharide. The short term goal will be optimization of the stereoselectivity of this reaction. A key aspect of this study requires the use of the aglucone substituent as a stereocontrolling element. In order to formulate a set of rules for predicting steroselectivity, the reactions of monosaccharide alkenes in which the size, electronic properties and configuration of the aglycone are varied, will be performed. Simultaneously the activating or deactivating effects of aglycone structure on the rate of the reaction will be noted. The rules for predicting steroselectivity and reactivity will be subsequently incorporated into a novel plan for the preparation of adjacently linked polyether, containing up to four units, from bis- saccharide alkene precursors. Due to its carbohydrate origin, this methodology will be especially suitable for preparation of highly hydroxylate polyether derivatives. In addition, the convergent nature of the plan and the availability of naturally occurring sugars of diverse substitution pattern facilitates a high degree of structural 'fine tuning', making the method attractive for drug analog production.