BIOSYNTHESIS - PART 28 - COLCHICINE - DEFINITION OF INTERMEDIATES BETWEEN O-METHYLANDROCYMBINE AND COLCHICINE AND STUDIES ON SPECIOSINE

Labelled samples are prepared of demecolcine 3, colchicine 4, N-formyl -N-deacetylcolchicine 6 and N-deacetylcolchicine 7, the last depending on a new method for its preparation from colchicine, Incorporation ex periments with these compounds and with specifically labelled autumnal ine 1 support the pathway 2 --> 5 --> 3 --> 6 --> 7 --> 4 as the termi nal sequence for the biosynthesis of colchicine, The key intermediate O-methylandrocymbine 2 is isolated from Colchicum autumnale plants tog ether with speciosine 14 and its O-acetyl derivative 15; all three are first isolations from this plant. Speciosine 14 and N-methyldemecolci ne 8 are shown to be formed in vivo largely from demecolcine 3 whereas N-formyldemecolcine 5 is the precursor of demecolcine and its N-formy l group is derived from C-3 of autumnaline. This discovery of a tropol one alkaloid which retains both carbons of the ethanamine bridge of 2 is important for future stereochemical work on the ring-expansion proc ess.