SYNTHETIC STUDIES TOWARDS ADJACENTLY LINKED POLYETHER ANTIBIOTICS

相邻连接的聚醚残基包括几个 天然产品的种类，具有广泛的重要意义 生物活动。在这些化合物中有离子载体 抗生素(抗球虫药物、心血管药物、抗艾滋病毒药物)和 乙酸根素(抗肿瘤)。这个项目的长期目标是 一种制备高密度脂蛋白的新方法的开发 组成这些化合物结构的取代聚醚。 合成计划是基于一种新的2，5-形成方法 二取代四氢呋喃(THF)。通过这个过程，一个 卤离子处理单糖烯基烯前驱体的研究 在水的条件下，直接转化为高度取代的卤素- 四氢呋喃甲醛。这种反应是基于邻近群体的参与 通过单糖的环氧键。短期目标将是 优化了该反应的立体选择性。的一个关键方面 这项研究需要使用龙舌兰酮取代基作为 立体控制元素。为了制定一套规则， 预测立体选择性，单糖烯的反应 糖苷元的大小、电子性质和构型 都是多种多样的，都将被表演。同时激活或 苷元结构对反应速度的钝化作用 将会被注意到。 预测立体选择性和反应性的规则将是 随后纳入了一项新的计划，以编制 邻位连接的聚醚，最多含有四个单元，来自双- 糖烯前体。由于它的碳水化合物来源，这 方法学将特别适合于高纯度的制备 羟基化聚醚衍生物。此外，趋同的性质 该计划和各种天然糖类的可用性 替代模式促进了高度的结构精细化 调整‘，使该方法对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.