Synthesising complex natural products
Many biologically active molecules, such as morphine, contain the morphan moiety, which has a structure of a fused bicycle. This structure is also present in the Daphniphyllum alkaloids, isolated from Daphniphyllum Yunnanese, a plant endemic to China's Yunnan province. The natural compounds Daphniyunnine B and D exhibit cytotoxic activity toward a variety of cancer cell lines, including leukaemia and lung cancer. The thorough investigation of these compounds is inhibited by their low (below 0.005 %) concentration in the source plant. A strategy for the total synthesis of these alkaloids has not yet been developed. With EU funding, the project ORCASYN aimed to perform the synthesis of such natural compounds. Project work was dedicated to developing a synthetic strategy to obtain several intermediates to progress to the complete natural compounds. Two strategies were compared for bicyclic core molecule synthesis: organocatalysis and gold catalysis. The bicyclic molecules were successfully assembled into a tetracyclic core, which gave rise to a pentacycle. The developed strategy enables rapid entrance toward structurally intricate intermediates. The multistage state-of-the art organic synthesis represents a set of novel methodologies, impacting scientists around the world and advancing synthesis of natural compounds.