TOTAL SYNTHESIS OF NATURAL (-)-PTAQUILOSIN, THE AGLYCON OF A POTENT BRACKEN CARCINOGEN PTAQUILOSIDE, AND THE (+)-ENANTIOMER AND THEIR DNA CLEAVING ACTIVITIES

The total synthesis of natural (-)-ptaquilosin (2) the aglycon of a potent carcinogen ptaquiloside (1) from bracken fern and its (+)-enantiomer (2) has been achieved starting with (+)-dimenthyl (1R,2R)-cyclopentane-1,2-dicarboxylate. The synthesis proceeds in 20 steps (2.9% overall yield). The key features of the synthesis are as follows: (i) diastereoselective alkylation of a common chiral compound 5 under different conditions has provided each of two diastereomers 6a and 6b predominantly, the former 6a eventually leading to natural (-)-2 and the latter 6b giving unnatural (+)-2 and (ii) the deformylative oxidation reaction of aldehyde 23 has been effected under the conditions mild enough to permit survival of the unstable product ptaquilosin (2). As to the DNA cleaving activities, dienone 4 prepared from natural (-)-ptaquilosin (2) was shown to be more efficient than dienone 4 derived from unnatural (+)-ptaquilosin (2).