New Colchicinoids from a Native Jordanian Meadow Saffron, Colchicum b rachyphyllum:  Isolation of the First Naturally Occurring Dextrorotatory Colchicinoid

As part of our continuing investigation of Jordanian Colchicum species, the biologically active components of Colchicum brachyphyllum were pursued. Using bioactivity-directed fractionation, nine colchicinoids were isolated and characterized. One of these has a novel ring system, to which we have ascribed the trivial name (+)-demecolcinone (9), and it represents the first naturally occurring dextrorotatory colchicinoid. Another isolated compound was a new colchicinoid analogue, (−)-2,3-didemethyldemecolcine (8), while the remaining seven known colchicinoids were new to the species: (−)-colchicine (1), (−)-3-demethylcolchicine (2), (−)-cornigerine (3), β-lumicolchicine (4), (−)-androbiphenyline (5), (−)-demecolcine (6), and (−)-3-demethyldemecolcine (7). The brine shrimp lethality test was used to direct the isolation of these colchicinoids. Moreover, all pure compounds were evaluated for cytotoxicity against a human cancer cell panel, for antimicrobial activity in an array of bacteria and fungi (including yeast), and for their potential to be allosteric modulators of the γ-aminobutyric acid type A receptor.