Bio-inspired synthesis and bioactivities of phenylethanoid glycoside crenatosides

Abstract

Herein, we report an effective approach for the synthesis of phenylethanoid glycosides bearing a fused 1,4-dioxane motif, employing a bio-inspired oxidative cyclization of the glucose 2′-OH and benzylic carbon of phenylethanol aglycone as a key step. Thus, crenatoside (1), isocrenatoside (2), and 20 analogs with varied substitution on the peripheral phenyl rings are synthesized. Some of the synthetic glycosides show considerable anti-inflammatory and immunosuppressive activities, and compound 36 exhibited the most potent immunosuppressive activity, with an IC₅₀ value of 19.9 μM on B lymphocyte proliferation responses.