The primary objective of this research program is to develop a practical synthesis of leucascandrolide A (1), a novel marine macrolide isolated by Pietra in 1996. In preliminary in vitro studies, leucascandrolide A deisplayed a potent cytotoxicity, and strong inhibition of the pathogenic yeast Candida albicans. Due to the difficulty of isolation of leucascandrolide A, combined with the presently unknown biogenetic origin, an efficient chemical synthesis represents the only viable approach to this rare natural product. Having completed the synthesis of the C(1)-C(15) fragment of this natural product, we propose a convergent, fully stereocontrolled synthetic approach to leucascandrolide A, suitable for the production of sufficient amount of this natural product for a comprehensive biological evaluation. In addition, we will develop the new synthetic methods including asymmetric Prins desymmetrization, tandem and catalytic asymmetric hydrosilylations, designed to provide an access to a variety of valuable synthetic intermediates. Starting at the level of basic research in organic and organometallic synthesis, it is our ultimate objective to provide new directions for the development of new anticancer therapeutic agents.
| Ulanovskaya, Olesya A; Janjic, Jelena; Suzuki, Masato et al. (2008) Synthesis enables identification of the cellular target of leucascandrolide A and neopeltolide. Nat Chem Biol 4:418-24 |
| Wang, Ying; Janjic, Jelena; Kozmin, Sergey A (2002) Synthesis of leucascandrolide A via a spontaneous macrolactolization. J Am Chem Soc 124:13670-1 |
