Studies towards the total synthesis of the macrocyclic diamine alkaloid haliclonacyclamine C

Abstract

Marine sponges produce a series of complex polycyclic diamine alkaloids which appear to have a common biogenesis from simple bis-pyridine macrocycles. These structurally novel secondary metabolites are presumably biosynthetically produced by the controlled ionic coupling of macrocyclic 3-alkyl piperidines leading to 3,4??-linked bis-piperidines (ii). Included among these diamine marine alkaloids is haliclonacyclamine C (i) which serves as our synthetic target. Chapter I in this thesis provides background information describing biological activity and proposed biosynthetic pathways to these important diamine marine alkaloids. Chapter II details progress towards the total synthesis of haliclonacyclamine C. The focus of Chapter II will be on our successful construction of the 3,4??-linked bispiperidine central core (ii) highlighted by the use of palladium-mediated C-C bond forming processes. The stereoselective hydrogenation of a coupled product will also be discussed.