The overall objectives of this proposal are 1) to synthesize a population of taurine analogs which may be used to delineate the mechanism of action by which taurine exerts its effects on the ATP-dependent calcium uptake system in the retina and 2) to synthesize specific inhibitors of taurine biosynthesis to determine the role biosynthesized taurine plays within retinal tissue. Synthetic methodology based upon established procedures and novel heterocycloadditions will be utilized to prepare the target moleucles. The target molecules are novel compounds and are both biologically and chemically significant. Chemically, this proposal impacts on several areas of synthetic chemistry. It will provide additional information about the regioselectivity, reactivity, and synthetic utility of 1-aza-1,3-diene equivalents in cycloaddition reactions when applied to heterocyclic systems. The synthesis of -methylenesulfonic acid esters represents new chemistry with wide applicability. The inhibitors of taurine biosynthesis proposed herein will be the first specific inhibitors of the cysteine sulfinic acid decarboxylase (CSAD). The cyclopropane analogs of taurine proposed herein are functionalized molecules which will be obtained in a stereospecific manner. Biologically, this proposal will provide important information regarding the role(s) taurine plays to maintain the structural integrity of photoreceptors and to modulate calcium flux in retinal tissue. This information will lead to a better understanding of how taurine protects the retina against retinal degeneration, which results from either a taurine deficient diet or an intense and prolonged light exposure.
