Synthesis of (-) - Indolactam V for the Total Synthesis of Cytoblastin

Cytoblastin is a rare drug used as an effective treatment for Aids-HIV cancer, non-Hodgkin’s lymphoma, lung cancer, melanoma, testicular cancer, and vulva cancer. Although cytoblastin is a useful drug, current methods of synthesizing cytoblastin are low yielding and not enantioselective. In this research project, (-)-indolactam V, a precursor of cytoblastin, is attempted to be synthesized, so it can be used in subsequent reactions to synthesize cytoblastin. Initially, the first route to synthesize (-)-indolactam V was via a Cu catalyzed arylation of the 4 position in 4-bromoindole, followed by peptide coupling of amino acids, and finally a ring closure. However, due to a failure in the Cu catalyzed arylation reaction and its discovered complications the route was abandoned in favor of a second route. Currently, the second route involving a conjugate addition in the 3 position in 4-bromoindole, followed by peptide coupling of amino acids, and finally a ring closure via Buchwald-Hartwig coupling is found to be more successful. In the second route, 2 molecules in the synthesis have been successfully synthesize. Future work in this project will be to push the synthesis as far as possible and successfully create the xPhos catalyst for the ring closure step.