NOVEL ORGANOMETALLIC ROUTES TO POLYENES & DERIVATIVES

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The broad, long term objectives of the proposed work are to provide short, rapid approaches to the construction of several polyene-containing natural products. Three unrelated types of polyene relationships are to be addressed: (1) all E, conjugated polyolefins; (2) skipped Z-polyenes; and (3) doubly skipped, polyprenoidal polyolefins. Specifically, the former classification will impact on polyene macrolide total synthesis. These large ring natural products are widely used as clinical agents for treatment of systemic infection. Skipped polyenes, with potential applications to e.g., pheromones and molecules derived from the arachidonic acid cascade (such as the slow reacting substances of anaphylaxis, SRSA's), the latter being especially prominent in their association with respiratory ailments. Coenzymes Qn, which make up a group of ubiquitous redox components intimately involved in the mitochondrial respiratory chain, are used clinically as well. The heart of the approach to these potent bimolecules lies in the further development of newly discovered organometallic methodology, with applications envisioned for effecting polyene construction via appropriately designed lynchpins. Taking advantage of either symmetry elements or differences in reactivity profiles between the termini of the novel lynchpins, 1-pot stitching via reagents preformed 'in-situ' with suitable electrophiles is to afford key components of the target molecules. Further extension of this new chemistry to the direct preparation of homochiral C-4-substituted (dideoxy) riboses is also envisioned.