Part I. Synthetic studies on xestospongin A, C and their analogs. Part II. Synthetic efforts towards a total synthesis of communesin B (a.k.a. nomofungin)

This thesis is comprised of work on two projects. The first involves study of methylated analogs of xestospongin A and C. The second is a study toward a total synthesis of communesin B.; Xestospongin A and C are the natural products isolated from a marine sponge. Xestospongin C is a potent IP3 mediated Ca++ release blocker. The absolute configurations of xestospongin A and C are still ambiguous. In this thesis, we clarified this ambiguity and found the origin of error in the previous misassignment. With the assistance of MacroModel computations, methylated analogs were designed to change the thermodynamic stability of xestospongin A and C conformations, and make it favor the less stable but more interesting xestospongin C conformation. C11 and C8 methylated analogs of xestospongin A and C were prepared in ∼20 steps. C8 methylated analog successively chose the less favored cis-decalin-like oxaquinolizidine (xestospongin C conformation) over the trans partner.; Studies directed toward total synthesis of communesin B were discussed. O-azaxylylene generation via a 1,5-H shift was developed. New amidine formation was developed by coupling an amide and an azide with the assistance of Lawesson's reagent or Lewis acids. The backbone fragment of the natural product was prepared in 13 steps. The final cyclization step is underway.