Question

Though salicylic acid is the physiologically active chemical ingredient in aspirin, consumer aspirin formulations are actually sold as a “derivatized” form of salicylic acid known as acetylsalicylic acid. Describe in detail the chemistry by which this aspirin formulation is synthesized and explain why we don’t just ingest aspirin composed of salicylic acid. After all, humans have been chewing on and making teas of willow bark to get the benefits of salicylic acid for thousands of years. What is the rationale? Also use your vast knowledge of biochemistry acquired during the course to explain how the pharmacologically active salicylic acid molecule actually makes its way into the bloodstream where it is needed for anti-inflammation, fever reduction, pain relief and blood thinning etc.

Answer 1

Aspirin (acetyl salicylic acid, ASA) formulation starts with salicylic acid (SA). The SA is acetylated at its phenolic group by use of acetic anhydride with an acid catalyst. The acid first activates the carbonyl group in the acetic anhydride to make the carbon susceptble to nucelophilic attack. The oxygen in the phenol group attacks one of the carbonyl carbons of the acetic anhydride. With an excess of the acid catallyst, a moiety of acetic acid leaves leaving behind the ASA. Although SA is the active anti-inflamatory agent, consumption by ingestion is not advisable to due its stringent and acidic properties which can easily damage the digesrive system. On the other hand, ASA is less acidic and can be ingested safely without immediate damage being incurred. Furthermore, the ASA can be transformed back to SA through acid catalyzed hydrolysis which is very much likely to happen in the stomach with the presence of acidic gastric juices.

Willow bark tree consumption to get the benefits of SA is nothing more but another type of derivatization, SA can be produced by human body acid catalyzed hydrolysis and oxidation of the salicin present in the willow barks.

The SA, after being slowly synthesized by the body, enters the blood stream. In its protonated form, the SA is predominantly solid. However, the alkalinity of the blood makes converts it to its corresponding salt form and making its solubility in aqueous media greater.