C5'-Alkyl Substitution Effects on Digitoxigenin α-L-Glycoside Cancer Cytotoxicity

摘要

A highly regio- and stereoselective asymmetric synthesis of various C5'-alkyl side chains of rhamnosyl- and amicetosyl-digitoxigenin analogues has been established via palladium-catalyzed glycosylation with postglycosylated dihydroxylation or diimide reduction. The C5'-methyl group in both α-L-rhamnose and α-L-amicetose digitoxin analogues displayed a steric directed apoptosis induction and tumor growth inhibition against nonsmall cell human lung cancer cells (NCI-H460). The antitumor activity is significantly reduced when the steric hindrance is increased at the C5'-stereocenter.