The total synthesis of antimalarial natural products, yaoundamines A and B isolated from Ancistrocladus korupensis will be attempted. Either yaoundamine A or B can serve as a lead compound for the development of antiparasitic compounds for therapeutic use. Yaoundamine B contains an unprecedented L rhamnose carbohydrate domain while yaoundamine A is devoid of such moiety. The initial synthesis will utilize a palladium catalyzed Suzuki cross-coupling of a naphthyl boronic acid and a chiral bromo tetrahydroisoquinoline followed by a stereoselective glycosylation. Although the tetrahydroisoquinoline is chiral, the stereocenters are far removed from the biaryl bond formed in the Suzuki coupling and are not expected to influence the conformation of the cross-coupling product. The carbohydrate moiety and additional chiral auxiliaries bonded to the isoquinoline will be investigated for their ability to induce stereocontrol during the biaryl bond forming reaction. Additionally, a previously unexplored intramolecular variant of the Suzuki reaction has been proposed to facilitate atroselectivity in the construction of the chiral biaryl axis.
| Keding, Stacy J; Danishefsky, Samuel J (2004) Prospects for total synthesis: a vision for a totally synthetic vaccine targeting epithelial tumors. Proc Natl Acad Sci U S A 101:11937-42 |
| Warren, J David; Miller, Justin S; Keding, Stacy J et al. (2004) Toward fully synthetic glycoproteins by ultimately convergent routes: a solution to a long-standing problem. J Am Chem Soc 126:6576-8 |
