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 experiments with these compounds and with specifically labelled autumnaline 1 support the pathway 2 --> 5 --> 3 --> 6 --> 7 --> 4 as the terminal sequence for the biosynthesis of colchicine, The key intermediate O-methylandrocymbine 2 is isolated from Colchicum autumnale plants together with speciosine 14 and its O-acetyl derivative 15; all three are first isolations from this plant. Speciosine 14 and N-methyldemecolcine 8 are shown to be formed in vivo largely from demecolcine 3 whereas N-formyldemecolcine 5 is the precursor of demecolcine and its N-formyl group is derived from C-3 of autumnaline. This discovery of a tropolone alkaloid which retains both carbons of the ethanamine bridge of 2 is important for future stereochemical work on the ring-expansion process.