C5'-Alkyl Substitution Effects on Digitoxigenin α-l-Glycoside Cancer Cytotoxicity.
Wang HY, Qi Z, Wu B, Kang SW, Rojanasakul Y, O'Doherty GA.
A highly regio- and stereo-selective asymmetric synthesis of various C5'-alkyl side chains of rhamnosyl- and amicetosyl-digitoxigenin analogs has been established via palladium-catalyzed glycosylation with post-glycosylated dihydroxylation or diimide reduction. The C5'-methyl group in both α-l-rhamnose and α-l-amicetose digitoxin analogs displayed a steric directed apoptosis induction and tumor growth inhibition against non-small cell human lung cancer cells (NCI-H460). The anti-tumor activity is significantly reduced when the steric hindrance is increased at C5'-stereocenter.