Towards the biomimetic total synthesis of Meiogynine

Meiogynine 1a is a natural terpenic compound that has been isolated by our team from the barks of Meiogyne cylindrocarpa, a Malaysian Annonaceae. It is characterized by the presence of a cis decaline whose all substituants are syn, an exocyclic trisubstitued double bond as well as five asymmetric centres. To date, only its relative configuration is known. Meiogynine displays significant cytotoxicity against KB and L1210 cell lines and inhibits Bcl-XL protein, an anti-apoptotic protein of the Bcl-2 family. As this protein, because of its key role in apoptosis, constitutes an attractive target for the development of new anticancer agents, the total synthesis of meiogynine as well as structure-activity relationships were envisaged.

Our synthetic approach is based on a biomimetic hypothesis of dimerisation between two bisabolane or zingiberene-type subunits. This synthesis, as well as structure-activity relationships have been studied.