FULLY REGIOCONTROLLED SYNTHESIS OF (PLUS-OR-MINUS)-12A,12B-SECOCOLCHICINE AND STUDIES CONCERNING ITS CYCLIZATION TO THE ALKALOID COLCHICINE

A fully regiocontrolled synthesis of the title compound 6, an AC-ring analogue of the alkaloid colchicine 1, is reported. The key step associated with the sequence used was condensation of lithium halogenocarbenoid 10-a synthetic equivalent for the inaccessible 7-methoxytropon-3-yl anion 12- with 3,4,5-trimethoxycinnamaldehyde 17 to produce the 1,2-addition product 18 as a mixture of diastereoisomers. Elaboration of compound 18 provided benzoate 23 which, on treatment with base, underwent ring-expansion to give troponoid 24 in excellent yield. Replacement of the C-7 benzoate group in compound 24 by an acetamido moiety was readily achieved and produced compound 6 in good overall yield. Unsuccessful attempts to convert compound 6 and the deacetamido analogue 38 into colchicine and deacetamidocolchicine 3, respectively, are described.