Ac. Barker et al., BIOSYNTHESIS - PART 28 - COLCHICINE - DEFINITION OF INTERMEDIATES BETWEEN O-METHYLANDROCYMBINE AND COLCHICINE AND STUDIES ON SPECIOSINE, Journal of the Chemical Society. Perkin transactions. I (Print), (18), 1998, pp. 2989-2994
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.