^{The total synthesis of various biologically important natural products is an important part of my group’s research. Our underlying interests include the development of new synthetic methodologies as well as the opportunity to establish important structure-function relationships for these rare natural products with medicinal significance. One example is our work on laulimalide. We achieved the first synthesis of this sponge-derived macrolide that has been isolated in only miniscule quantities. Our chemical synthesis of laulimalide enabled us to carry out further biological studies in collaboration with Dr. Ernie Hamel at the National Cancer Institute. While laulimalide was thought to resemble paclitaxel in its effects on cellular microtubules, our studies established that laulimalide stabilizes microtubules by binding at a novel site on the tubulin dimer. Laulimalide appears to be the first example of a ligand for this hitherto unknown drug-binding site. In addition, laulimalide was able to enhance tubulin assembly synergistically with paclitaxel. Furthermore, we have shown that the epoxide functionality is not essential for activity as our synthetic desoxylaulimalide has shown similar potency as laulimalide. We have also demonstrated that peloruside A, B, and zampanolide are novel microtubule stabilizing agents. We have carried out efficient laboratory syntheses of these important anticancer natural products and are currently investigating in-depth biology of various structural variants.
     Over the years, my research group has completed the synthesis of many other biologically important natural products including: anticancer agents such as Amphidinolide T, Amphidinolide W, Spongidepsin, Cryptophysin B, Cryptophysin 52, and Doliculide, MDR- inhibitor Hapalosin, streptogramin antibiotic Madumycin, pancreatic lipase inhibitor, tetrahydrolipstatin, antimalarial agent boronolide, gastroprotective agent, AI-77-B, reverse transcriptase inhibitor, taurospongin, nucloside antibiotic sinefungin, polyoxin-J, peloruside A, largazole, platensimycins and herboxadine. We have also completed the synthesis of (-)-lasonolide A. In collaboration with Dr. Yves Pommier at the NCI, we recently showed that lasonolide possesses a novel chromosome condensing ability. Using synthetic lasonolide and its structural variants, we are now investigating their biological mechanism of action.}