The aims of this proposal are multifaceted. One area of activity will be devoted to probing possible relationships between di-, tri-, and tetraepoxides of unusual structure and tumor-inhibitory activity. This effort will require the development of innovative approaches to new polycyclic polyolefins. Also to be prepared are new optically active ferrocenes and ferrocenium salts, the goal being to gain improved appreciation of the antineoplastic potential of this class of compounds and to develop them into useful new tools for asymmetric synthesis. Because ingenol esters exhibit pronounced cocarcinogenic or antileukemic properties, a number of members of this group and their structural analogues (particularly the 8-epi series) have been targeted for total synthesis. Dolatriol and several related diterpenes of marine origin, compounds that exhibit impressive cytotoxic activity, also have been affirmed as synthetic objectives. In yet a very different arena, synthetic approaches to a number of furanocembranolides, recognized for their potent biological effects, will be undertaken.
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