Extracts of Stemona and Croomia species have been used in Chinese and Japanese folk medicine as drugs for the treatment of respiratory diseases such as bronchitis, pertussis and tuberculosis. The biological activity of Stemona alkaloids as insecticides and antihelmintics, for example against silk worm larvae, is promising. Recently, applications as nontoxic agents for insect control in cotton and vegetables and fruit preservation were reported. The major Stemona alkaloid, tuberostemonine, also inhibits excitatory transmission at the crayfish neuromuscular junction. Quite possibly, some of the exceptional effects of crude extracts of Stemona are due to minor components, and the search for therapeutically active members of this novel class of alkaloids is far from being completed. To date, the structures of more than twenty Stemona and Croomia alkaloids have been elucidated by crystallographic, spectroscopic and degradative techniques. Although a few synthetic approaches towards stenine, the simplest Stemona alkaloid, have been described, none of the more complex members of this family has been prepared. The proposed research program will achieve the following goals: 1. Development of a unified synthetic strategy and methodology sufficient for the construction of the core systems of Stemona and related alkaloids. 2. The first asymmetric syntheses of stenine and tuberostemonine, the major structural isomers of the Stemona family. 3. Establishment of a versatile chemistry of oxidized tyrosine derivatives that is generally applicable for the stereospecific preparation of indole and pyrrolidine alkaloids and can be extended to indolizidine and pyrrolizidine natural products. The polycyclic cores of Stemona alkaloids pose challenging synthetic problems. Much of the future application of;these promising agents will depend on a thorough understanding of their molecular properties and chemical reactivity. A straight forward synthetic approach towards this class of alkaloids will provide the necessary basis for intensified structural investigation of their highly attractive spectrum of therapeutic effects.
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