Synthesis of Salicaceae Acetyl Salicins Using Selective Deacetylation and Acetyl Group Migration

In the present work, the synthesis of acetylated salicins, which occur naturally in many Salicaceae species, is reported. The preparation of 2-O-acetylsalicin, 2-O-acetylchlorosalicin, and 2-O-acetylethylsalicin from peracetylated bromosalicin with selective acid-catalyzed deacetylation and one-pot nucleophilic substitution of bromine as the key steps is described. The base-catalyzed O-2 → O-6 acetyl migration afforded 6-O-acetylsalicin derivatives in good yields. Thus, the first synthesis of 6-O-acetylsalicin (fragilin) using acetyl group migration is reported as well as the synthesis of 6-O-acetylchlorosalicin and 6-O-acetylethylsalicin. The NaOMe-catalyzed deacetylation of acetylated glycosides gave salicin, chlorosalicin, and ethylsalicin recently reported from Alangium chinense.