Novel reaction products from the hypervalent iodine oxidation of hydroxylated stilbenes and isoflavones.
Novel reaction pathways for the hypervalent iodine-mediated oxidation of bioactive phenols containing extended conjugated pi-systems are described. Oxidation of 4-hydroxystilbenes in methanol using a hypervalent iodine-based oxidant led to the formal 1,2-addition of methoxy groups across the central stilbene double bond. Treatment of the structurally related 4-hydroxyisoflavone with di(trifluoroacetoxy)iodobenzene leads to the surprising formation of 2,4'-dihydroxybenzil. Potential mechanisms for these new reaction pathways are discussed, and the X-ray crystal structure of 2,4'-dihydroxybenzil is presented. In contrast, oxidation of the corresponding 3-hydroxystilbenes and 3-hydroxyisoflavone led to conventional dienone oxidation products. The antitumour implications of these oxidation processes are briefly highlighted; the novel 4-substituted phenolic oxidation products were found to be inactive in terms of in vitro antitumour cellular activity, whereas the 3-substituted phenol products gave novel agents with potent and enhanced antitumour activity in the HCT 116 cancer cell line.
Lion
Cedric J
CJ
Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, UK.
Vasselin
David A
DA
Schwalbe
Carl H
CH
Matthews
Charles S
CS
Stevens
Malcolm F G
MF
Westwell
Andrew D
AD
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D006801:Humans; D007455:Iodine / Q000737:chemistry; D007529:Isoflavones / Q000138:chemical synthesis* / Q000494:pharmacology; D010636:Phenols; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007529:Isoflavones; D010636:Phenols; D013267:Stilbenes; D007455:Iodine