Synthesis of verbascoside: A dihydroxyphenylethyl glycoside with diverse bioactivity

TMSOTf-mediated condensation of ethyl 4,6-O-benzylidene-1-thio-beta-D-gluco pyranoside (2) with peracetylated alpha-L-rhamnopyranosyl trichloroacetimid ate donor 3a resulted in the formation of orthoester 4, which, after acetyl ation, rearranged into ethyl 3-O-(alpha-L-rhamnopyranosyl)-1-thio-beta-D-gl ucopyranoside derivative 6a. The latter compound was converted into the cor responding trichloroacetimidate donors 8a-b. An alternative approach to tri chloroacetimidate 8c commenced with the iodonium ion mediated glycosidation of ethyl 2,3,4-tri-O-benzoyl-1-thio-alpha-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-butyldimethylsilyloxy)phenyl]ethanol (12) gave, after deacylation, ke y intermediate 14. Protecting-group manipulation of 14 and subsequent ester ification of resulting 22 with 3,4-di-O-tert-butyldimethylsilylcaffeic acid (27) gave, after deprotection, verbascoside (1).