Synthesis and separation of potential anticancer active dihalocephalomannine diastereomers from extracts of Taxus yunnanensis.

Two diastereomeric 2",3"-dibromo cephalomannines and their two corresponding 7-epimers were obtained by treatment of extracts of Taxus yunnanensis with bromine solution under mild conditions. Treatment of the same extract with chlorine solution yielded four diasteromeric 2",3"-dichlorocephalomannines, with no 7-epimers. The diastereomeric mixtures were separated into the individual components by preparative HPLC on C18 reversed-phase silica gel. A more efficient analytical separation was obtained on a pentafluorophenyl-bonded phase. These reaction products were isolated and fully identified spectroscopically. Slight differences were observed in the NMR spectra of the 7-epimers when compared to their 7 beta-OH analogues. On the basis of a comparison of physicochemical data, the bromo compounds were identified as (2"R,3"S)-dibromo-7-epi-cephalomannine (3), (2"S,3"R)-dibromo-7-epi-cephalomannine (4), (2"R,3"S)-dibromocephalomannine (5), and (2"S,3"R)-dibromocephalomannine (6), and the chloro compounds as (2"R,3"R)-dichlorocephalomannine (7), (2"S,3"S)-dichlorocephalomannine (8), (2"R,3"S)-dichlorocephalomannine (9), and (2"S,3"R)-dichlorocephalomannine (10). Cytotoxic activity was tested against the NCI 60 human tumor cell line panel in comparison with paclitaxel (1), and encouraging results were obtained in some cases.