Cycloadditions of 4-pyrones. An approach to colchicine

Article abstract of DOI:10.1016/S0040-4020(01)80383-5

The 4-pyrone, [5-acetoxy-4-oxo-4H-pyran-2-yl]carbonyl chloride was coupled with the malonate anion of bis(2,2,2-trichloroethyl) 2-ethenyl-3,4,5-trimethoxybenzylpropanedioate and analogs thereof. These adducts then underwent intramolecular thermal cyclizations (61-100% yield) to form the two fused seven member rings of the carbon skeleton of colchicine. The malonate moiety was deprotected and decarboxylated quantitatively to provide the desired ring system which contained a bridging ether, from C7a to C11 in the C ring, and a ketone at the 7 position. Removal of the bridging ether as H2O would yield the desired tropolone. Our attempts to remove the ether bridge were unsuccessful.