The principal investigator notes that this revised proposal outlines the synthesis of a variety of unusual five-membered ring sulfur containing heterocycles. The key step in the synthesis of these compounds is to be a transition-metal mediated 3+2 cycloaddition reaction involving transition-metal substituted propargyl and allyl complexes and sulfur containing electrophiles. The stereoselectivity of these 3+2 cycloaddition reactions is to be studied during the course of this project and new demetallation reactions for liberating the heterocycle from the transition metal after cycloaddition are also to be explored. The heterocycles synthesized in this project are to be primarily thiosulfinate esters and thiophene thiones. It is stated that these types of molecules are not easily accessed cleanly through traditional synthetic organic chemistry and that these types of heterocycles and other structurally related ones occur naturally in some vegetables and many of them function as inducers of detoxification enzymes which are involved in the prevention of carcinogenesis. The sulfur containing heterocycles produced in this project are to be screened as detoxification enzyme inducers in Dr. Margie Clapper's laboratory at the Fox Chase Cancer Center.
