Acetylsalicylic acid from willow-derived salicylic

Salicylates are derivatives of 2-hydroxybenzoic acid (salicylic acid). They were discovered in 1838, following the extraction of salicylic acid from willow bark. Salicylic acid was used medicinally as the sodium salt but replaced therapeutically in the late 1800s by the acetylated derivative, acetylsalicylic acid (ASA), or aspirin (Figure 13.2). Therapeutie utility is enhanced by esterification of the phenolic (hydroxyl) group as in aspirin, and by substitution of a hydrophobic/lipophilic group at C-5 as in diflimisal. 

SAM-dependent methylation of salicylic acid. The salicyl alcohol derivative salicin, found in many species of willow (Salix species Salicaceae), is not derived from salicylic acid, but probably via glucosylation of salicylaldehyde and then reduction of the carbonyl (Figure 4.27). Salicin is responsible for the analgesic and antipyretic effects of willow barks, widely used for centuries, and the template for synthesis of acetylsalicylic acid (aspirin) (Figure 4.27) as a more effective analogue. 

Aspirin (acetylsalicylic acid) was introduced in 1899 it is by far the commonest form in which salicylate is taken. The bark of the willow tree (Salix) contains salicin from which salicylic acid is derived it was used for fevers in the 18th century as a cheap substitute for imported cinchona (quinine) bark. 

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