title: The cascade radical annulation approach to new analogues of camptothecins. Combinatorial synthesis of silatecans and homosilatecans.
abstract: An overview of the cascade radical annulation approach to the camptothecin family of antitumor drugs is presented. This combinatorial synthetic approach involves two key steps: (1) N-propargylation of a lactone/pyridone D/E ring fragment and (2) cascade radical annulation of an A-ring isonitrile to form rings B and C. The synthesis is probably the most flexible and general route to the camptothecin class of molecules. The parallel synthesis of several libraries of silatecan and homosilatecan libraries is summarized. One of the first-generation silatecans, DB-67, is emerging as a serious candidate for cancer chemotherapy.
authors.affiliation: Department of Chemistry and Center for Combinatorial Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. curran@pitt.edu
authors.forename: D P
authors.initials: DP
authors.lastname: Curran
authors.forename: H
authors.initials: H
authors.lastname: Josien
authors.forename: D
authors.initials: D
authors.lastname: Bom
authors.forename: A E
authors.initials: AE
authors.lastname: Gabarda
authors.forename: W
authors.initials: W
authors.lastname: Du
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006801:Humans
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D002166:Camptothecin