| Part I. Haterumalide NA (oocydin A) is a potent anti-fungal and cytotoxic agent isolated from two related bacteria (Serratia marcescens and Serratia plymuthica) and from an unrelated Okinawan sponge. We have synthesized the 14-membered lactone core structure. We have proposed two fundamentally distinct synthetic strategies based on the order of macrocyclization vs smaller ring formation. After ring closing metathesis (RCM) and relay ring closing metathesis (RRCM) approach failed to cyclize macrocycle in strategy I, we successfully closed the macrocycle by unprecedented intramolecular palladium catalyzed chloroallylation. The other key steps include Roush [2+3] cyclization, Woerpel-Tamao oxidation, Keck allylation, and selective Luche reduction.; Part II. Spirchostain A and B are novel bicyclic depsipeptides isolated from Pseudomonas sp. They mimic transforming growth factor-beta (TGF-beta), which suppresses growth of various tumor cell lines. When we started this study, the configurations of three of the five stereocenters in the cyclic depsipeptide skeleton were unknown. We used variable temperature 1HNMR experiments, mixed solvents, and resolution enhancement operations to decipher the entire set of vicinal and allylic coupling constants (Js).; Part III. Latrunculin A and B, isolated from the Red Sea sponge, Latrunculia maginifica, are active actin polymerization inhibitors. Three types of analogs have been designed based upon the analysis of X-ray structure of the latrunculin-actin complex. The amacrocyclic analog has been synthesized by twelve steps, which include 1,3-diketone formation by acylation, pyrone formation by an acid promoted equilibration, and selective esterification. |
