Leukotrienes (LT's) are lipid metabolites which act as broncho and vasoconstrictors and are known to increase vascular permeability. Findings indicate that inhibitors toward the in vivo formation of leukotrienes could be of therapeutic value in the treatment of bronchial asthma and allergic reactions. Due to the low natural abundance of the LT's, only the availability of synthetic leukotrienes and leukotriene derivatives will permit future mechanistic studies of the biological action and metabolism of these important bio-molecules. The leukotriene structure presents two synthetic challenges--the cis-divinylmethane functionality and the stereospecific introduction of allylic oxygen functionality. New synthetic methodology will be developed to address these two challenges by taking advantage of 1) the facile preparation, resolution, and reactivity of chiral (diene) iron cations with nucleophiles to afford trans,cis-1,3-dienes. Since the conjugated triene portion of the leukotriene structure is known to be extremely susceptible to air oxidation, the """"""""protection"""""""" of the polyene by complexation to iron will be a tremendous advantage in the preparation and handling of these sensitive compounds. A growing new class of antibiotics are the polyene macrolides. These compounds are characterized by a conjugated polyene segment (4-7 double bands) as well as adjacent segments containing up to four contiguous chiral centers. New synthetic methodology will be developed for the asymmetric synthesis of these centers utilizing an originally prochiral diene. This will be accomplished through complexation to the stereochemically directing iron(tricarbonyl) adjunct.
