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.
| Pauls, H W; Fraser-Reid, B (1986) Stereocontrolled routes to cis-hydroxyamino sugars, Part VII: Synthesis of daunosamine and ristosamine. Carbohydr Res 150:111-9 |
