Synthesis Of C-2,C-3-Iso-deoxypodophyllotoxin And Its Anticancer Activities Study

Podophyllotoxin as well as its derivatives exhibit excellent biological activitives,mainly including anti-tumor and anti-virus.However,the side effects of podophyllotoxin are so strong that it cannot be used directly as a drug.Compared with podophyllotoxin,deoxypodophyllotoxin,a family product of podophyllotoxin,not only retains its anti-tumor activity but weakens the side effects,which drawn our attention on the synthesis and biological activitives of deoxypodophyllotoxin and its isomers.Based on the unique chemical structure of deoxypodophyllotoxin,we designed the synthetic route mainly focused one the construction of five-membered lactone ring and six-membered ring.In this paper,the key lactone intermediate was synthesized from piperanol by oxidation reaction,substitution reaction,conjugate addition and deprotection of the phenylthio groups.Then,two synthetic routes around key intermediate were designed to obtaine two isomers of deoxypodophyllotoxin.One of the synthetic route was to prepare the ?-aldehyde lactone structure from the key lactone via Claisen condensation.Subsequently,an intermolecular double Friedel-Crafts reaction was employed to establish the six-membered ring from the ?-aldehyde lactone and 1,2,3-trimethoxybenzene,and the target molecule deoxypodophyllotoxin could be received by this double Friedel-Crafts reaction.Another synthetic route was to obtain the benzyl hydroxyl compound from the aforementioned key lactone and 3,4,5-trimethoxybenzaldehyde through nucleophilic addition.Then,the corresponding C2,C3-deoxypodophyllotoxin isomer was accomplished through trifluoroacetic acid catalyzed intramolecular double Friedel-Crafts reaction from the the benzyl hydroxyl compound.Additionally,the antitumor activitives of the two deoxypodophyllotoxin isomers were tested.The results indicated that C2,C3-deoxypodophyllotoxin isomer showed certain inhibitory effect on lung cancer cell H1975,cervical cancer cells Hela and human breast cancer cells MCF-7.However,another isomer showed no inhibitory effect on the above-mentioned cancer cells.