Synthesis of Verbascoside: A Dihydroxyphenylethyl Glycoside with Diverse Bioactivity

Abstract

TMSOTf-mediated condensation of ethyl 4,6-O-benzylidene-1-thio-β-D-glucopyranoside (2) with peracetylated α-L-rhamnopyranosyl trichloroacetimidate donor 3a resulted in the formation of orthoester 4, which, after acetylation, rearranged into ethyl 3-O-(α-L-rhamnopyranosyl)-1-thio-β-D-glucopyranoside derivative 6a. The latter compound was converted into the corresponding trichloroacetimidate donors 8a–b. An alternative approach to trichloroacetimidate 8c commenced with the iodonium ion mediated glycosidation of ethyl 2,3,4-tri-O-benzoyl-1-thio-α-L-rhamnopyranside (15) with 1,2:5,6-diisopropylidene-D-glucofuranose (16) to afford disaccharide 17, which was transformed into 8c in five steps. Condensation of 8a–c with 2-[3,4-di-(tert-butyldimethyl-silyloxy)phenyl]ethanol (12) gave, after deacylation, key intermediate 14. Protecting-group manipulation of 14 and subsequent esterification of resulting 22 with 3,4-di-O-tert-butyldimethylsilylcaffeic acid (27) gave, after deprotection, verbascoside (1).