The chemical synthesis of bicyclic lactone analogs related to the oxygenated fragments found in several spongian diterpenes has been achieved. Structure activity relationship studies have identified bridged and fused bicyclic lactone analogs that initiate a unique pericentriolar localized Golgi fragmentation phenotype similar to that exhibited by the spongian diterpene macfarlandin E. These studies indicate that acetoxy-substitution adjacent to the lactone moiety is a key structural feature responsible for inducing the observed phenotype. The chemical reactivity of simplified bicyclic lactone fragments has also been investigated. Reaction of both the substituted dioxabicyclo[3.2.1]octanone and dioxabicyclo[3.3.0]octanone ring systems with a primary amine leads to pyrrole products. Exposure of hen egg white lysozyme to the bicyclic lactone analogs under biologically relevant conditions affords pyrrole conjugates.

Chemical reactivity and biological significance of bicyclic lactone analogs derived from rearranged spongian diterpenes

243rd National Meeting (2012)

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