Synthesis of colchifulvin, a colchicine–griseofulvin hybrid

Since the antimitotic agent colchicine (4) and the antifungal antibiotic griseofulvin (5) bind the same target (tubulin), we have explored the possibility of combining the potency of 4 and the low-toxicity of 5 into a hybrid [colchifulvin (6)], where the aromatic A-ring of 4 is bound to a dienone C-ring in a spiro fashion reminiscent of 5. To this purpose, the intramolecular oxidative cyclization of bibenzyl and stilbenoid precursors of spiro[4.5]decadienones was investigated, eventually taming the unexpected subtleties of the reaction. Disappointingly, rac-6 did not share the biological profile of the two inspiring lead structures.