Design and synthesis of lamellarin D analogues targeting topoisomerase I

Article abstract of DOI:10.1021/jo901589e

(Chemical Equation Presented) A general synthetic route to rationally designed lamellarinDanalogues, 1-dearyllamellarinD(1) and 1-substituted 1-dearyllamellarin D (2), has been developed. The key pentacyclic intermediate 22 was prepared by palladium-catalyzed direct arylation of 12, which in turn was synthesized via C-2-selective lithiation of 15 followed by palladium-catalyzed cross-coupling as the key reactions. Compound 22 was converted to a wide range of C-1-substituted analogues 2 via regioselective electrophilic substitution and palladium-catalyzed cross-coupling reactions.