In collaboration with colleagues at the Kitasato Institute (Japan), we recently determined the complete relative and absolute stereochemistry of chloropeptins I and II. These novel macrobicyclic heptapeptides inhibit the binding of the HIV gp120 envelope glycoprotein to the cluster determinant 4 (CD4) receptor of T-cell lymphocytes, a critical event in HIV infection leading to the onset of AIDS. Inhibitors of gp120-CD4 binding hold considerable promise an anti-HIV therapeutic agents. The principal goals of this research program are: (A) to devise an efficient, stereocontrolled total synthesis of chloropeptin I, focusing on atrodiastereoselectiove construction of the unique, axially chiral biaryl linkage; and (B) to design, synthesize, and test analogs of the chloropeptins in order to optimize the inhibition of gp-120-CD4 binding.
| Smith 3rd, Amos B; Chruma, Jason J; Han, Qiang et al. (2004) Complestatin synthetic studies; the effect of the amino acid configuration on peptide backbone conformation in the common western BCD macrocycle. Bioorg Med Chem Lett 14:1697-702 |
| Smith 3rd, A B; Kanoh, N; Minakawa, N et al. (1999) Tremorgenic indole alkaloids. Studies directed toward the assembly of the A, F, and I rings of penitrem D: observation of an unexpected stereochemical outcome. Org Lett 1:1263-6 |
