Total Synthesis of Phenylpropanoid Glycosides,Acteoside, Isoacteoside and Ligupurpuroside J

Phenylpropanoid glycosides (PPGs), a kind of natural glycosides with C6-C3 aromatic framework, are widely distributed in the plant kingdom. These glycosides show various medicinal properties, including antioxidative, antibacterial, antiviral and antitumor activities. Nevertheless, because of their low content in plants, the isolation of these compounds is a formidable task , so as to retard in-depth studies of their biological activities. Thus, the development of effective approaches to the synthesis of phenylpropanoid glycosides has attracted a great attention. Since the 1990s, several syntheses have been reported, however most of these synthetic routes are lengthy due to multi-step manipulations of protecting groups, especially some of the protecting groups/deprotecting reagents are incompatible with the alpha-beta-unsaturated ester occurring in PPGs. Here, we report a general and effective synthetic approach to PPGs. The present approach features a regioselective glycosylation of 2-phenylethyl glucoside polyols with rhamnosyl o-alkynylbenzoate donors under the catalysis of triphenyephosphinegold (I) bis (trifluormethanesulfonye) imidate (PPh3AuNTf2, 10%-15%, molar fraction) at low temperature to furnish the key alpha-(1 -> 3)-saccharides. Then, the 2-OH in the glucose unit was selectively protected with acetyl chloride, subsequent condensation with caffeic acid with the remaining C4-OH completed the major PPGs framework. Global removal of the acetyl and allyl groups afforded acteoside. Similar approaches were successfully applied to the synthesis of Isoacteoside and Ligupurposite J, which contained caffeic acid residue at the C6-OH of the glucose unit. The regioselective glycosylation, which avoids selective protection/deprotection of the hydroxyl groups, provides a shorter synthetic approach toward the PPGs.