Divergent Synthesis of Natural Benzyl Salicylate and Benzyl Gentisate Glucosides

Herein is reported the first total synthesis of benzyl salicylate and benzyl gentisate glucosides present in various plant species, in particular the Salixgenus, such as Populus balsamiferaand P. trichocarpa. The method permits the synthesis of several natural phenolic acid derivatives and their glucosides starting from salicylic or gentisic acid. The divergent approach afforded access to three different acetylated glucosides from a common synthetic intermediate. The key step in the total synthesis of naturally occurring glycosides—the selective deacetylation of the sugar moiety—was achieved in the presence of a labile benzyl ester group by employing mild deacetylation conditions. The protocol permitted synthesis of trichocarpine (4 steps, 40% overall yield), isotrichocarpine (3 steps, 51% overall yield), trichoside (6 steps, 40% overall yield), and deoxytrichocarpine (3 steps, 42% overall yield) for the first time (>95% purity). Also, the optimized mild deacetylation conditions allowed synthesis of 2-O-acetylated derivatives of all four glycosides (5–17% overall yield, 90–95% purity), which are rare plant metabolites.