TRICHOTHECANES, AMINO SUGARS, AND AVERMECTINS

这项研究项目涉及三个不同类别的 化合物、三十烷、氨基糖和阿维菌素。在.期间 在第一批赠款期间，关于三氯乙烷的工作卓有成效。 特别是关于大环系统。我们已经做出了 痤疮酚取得了重大进展，我们现在能够 探索D-葡萄糖的一些可选路线，这些路线不仅可以提供 以光学活性形式存在的三氯乙烷，但允许制备 几个改装过的系统。氨基糖的第一个授权期 也取得了巨大的成功，导致了石榴莲的合成， 全聚糖胺、西比罗萨胺、利多糖胺和柔酚胺。高度 使用烯丙基底物已经开发出了重要的方法 它承诺使顺式羟基的立体控制形成变得微不足道 地雷系统。在即将到来的授权期内，我们将努力 研究同源系统，以及一个特别吸引人的途径 硫那霉素就是按照这些思路构思出来的。关于第三个问题的研究 阿维菌素类化合物将在即将到来的 授权期。这里的主要挑战被认为是准备一个 OXA-HYDINDAN体系，可能通过两种方式容易自毁 贝塔淘汰赛。我们将调查碳水化合物系统的使用情况 不仅以光学活性形式提供氧-氢化物，而且还 防止即将到来的自我毁灭。阿维菌素的所有成分 都是由现成的糖衍生物制成的。三个都是 化合物的类别具有巨大的当前生物学意义，因为 抗肿瘤药物、抗生素或抗蠕虫药物。

This research program is concerned with three different classes of compounds, tricothecanes, amino sugars and the avermectins. During the first grant period work on the trichothecanes has been highly productive particularly with regard to the macrocyclic systems. We have made significant progress towards verrucarol and we are now in a position to explore a number of optional routes from D-glucose which will not only give the trichothecanes in optically active form, but will allow the preparation of several modified systems. The first grant period on the amino sugars has also been highly successful having lead to syntheses of garosamine, holocosamine, sibirosamine, ristosamine and daunosamine. Highly significant methodologies have been developed using allylic substrates which promise to trivialize the stereocontrolled formation of cis-hydroxy amine systems. In the forthcoming grant period we will strike out to investigate homoallylic systems, and a particularly appealing route to thienamycin has been conceived along these lines. Research on the third class of compounds, the avermectins, will be initiated in the forthcoming grant period. The main challenge here is seen to be the preparation of an oxa-hydrindane system which may be prone to self-destruction by way of two Beta-eliminations. We will investigate the use of carbohydrate systems not only to provide the oxa-hydrindane in optically active form, but also to prevent the impending self destruction. All components of the avermectins are to be prepared from readily available sugar derivatives. All three classes of compounds are of immense current biological interest as anti-tumor agents, antibiotics or anti-helminthic agents.