Studies toward the total synthesis of quartromicin D(3)

This dissertation describes research focusing on Diels-Alder reactions of acyclic (Z)-substituted-1,3-dienes toward the total synthesis and absolute stereochemical assignment of quartromicin D₃, a member of a family of compounds isolated in 1991 from an actinomycete species in Japan. Chapter I recounts the isolation and determination of in vitro antiviral activity of the quartromicins. In Chapter 11, asymmetric Lewis acid-catalyzed Diels-Alder reactions between an acyclic 1,1,3,4-( Z)-substituted-1,3-diene and two different chiral dienophiles are described, constituting the first examples of an enantioselective Diels-Alder reaction of a (Z)-substituted-1,3-diene. The synthesis of the endo-spirotetronate subunit of quartromicin D₃ is accomplished, as well as the formal synthesis of the exo-spirotetronate intermediate, starting from a common intermediate enol silane derived from the enantioselective Diels-Alder reaction of a ( Z)-substituted-1,3-diene. In addition, an alternative route for the exo-spirotetronate is reported which features organocerium additions to a neo-pentyl ketone and a selective ozonolysis of a mono- versus tri-substituted olefin. The relative reactivity of various (Z)-substituted dienes in Diels-Alder reactions is studied in Chapter III in order to gain a better understanding of the effect that diene architecture imparts upon reactivity in Diels-Alder reactions. Finally, Chapter IV presents future plans for completing the total synthesis and absolute stereostructure assignment of quartromicin D₃.