The goal of this proposal is to develop the epoxidation chemistry of allenes into improved synthetic methodology for the preparation of highly functionalized molecules of biological interest. This is focused on the generation of the corresponding allene diepoxides and the subsequent nucleophilic addition reactions of these reactive intermediates. The scope of this chemistry, including regio- and stereochemical features as well as its potential for use in chiral synthesis, will be defined for both inter- and intramolecular nucleophiles leading to polyfunctional products of acyclic and heterocyclic structure, respectively. Proposed applications to the synthesis of bioactive molecules include models for corticoid steroids, pyrrolidine and piperidine alkaloids, sugar, alkylidene lactones, and complex oxygenated tetrahydrofurans and -pyrans. The antimicrobial marine natural product Bissetone will be the target of a synthetic study illustrating this chemistry. The methodology to be developed will be of use in the synthesis of the various types of molecules cited and their analogs, especially those with a high degree of functionalization. Many of these compounds display important biological activity of therapeutic value including antibiotic, antineoplastic, specific enzyme inhibitory properties, etc. The results of this study should facilitate a better understanding of the nature and function of these materials.
