Synthesis of dihydroxyphenacyl glycosides for biological and medicinal study: β-oxoacteoside from Paulownia tomentosa

Abstract

The protected structure of β-oxoacteoside (tomentoside A), 2-oxo-2-(3,4-dihydroxyphenyl)ethyl 3-O-(2,3,4-tri-O-acetyl-α-l-rhamnopyranosyl)-4-O-caffeoyl-β-d-glucopyranoside 14 was synthesized in 14% overall yield in 11 steps, starting from d-glucose for biological and medicinal studies of phenylpropanoid glycosides. The first step was the preparation of a 3-O-rhamnopyranosyl disaccharide sugar core 2 from a suitably protected rhamnosyl trichloroacetimidate 10 and glucose derivative (diacetone-d-glucose 1) in 71% yield. To the glucose moiety of this sugar core, several protection/deprotection procedures were performed sequentially to obtain a fully acetylated sugar core 7 with a 4-OH group on the glucose moiety, in 57% yield in five steps. Thereafter, to the 4-OH group of the glucose moiety, selective 4-O-caffeoylation was achieved by proton-transfer esterification with 3,4-di-O-allylcaffeic acid 16 to give the caffeoyl disaccharide 11 in 97% yield. Then, it was converted to trichloroacetimidate 13 for a glycosylation donor in 90% in two steps. Finally, anomeric glycosylation was conducted with 2-oxo-2-(3,4-di-allyloxyphenyl)ethyl alcohol 19 with catalytic amounts of BF₃·Et₂O to give 2-oxo-2-(3,4-di-allyloxyphenyl)ethyl 2,6-di-O-acetyl-3-O-(2,3,4-tri-O-acetyl-α-l-rhamnopyranosyl)-4-O-(3,4-di-allyloxycaffeoyl)-β-d-glucopyranoside 14 in 60% yield. Deprotected intermediates of compounds 2, 11, 14, and 19 which were obtained in high yield would be useful for biological and medicinal studies of phenylpropanoid glycosides.