Aspirin transesterification

It was found that decomposition is in part due to transesterification and that substitution increases stability. The effect of gamma radiation on aspirin has been described.184 The pH stability profile of aspirin according to Edwards has been made the subject of a student experiment.185... 

The base used in the formulation of suppositories can often affect the rate of decomposition of the active ingredients. Aspirin decomposes in several polyoxyethylene glycols which are often incorporated into suppository bases. Degradation was shown to be due in part to transesterification, giving the decomposition products salicylic acid and acetylated polyethylene glycol. The rate of decomposition, which followed pseudo first-order kinetics, was considerably greater than when a fatty base such as cocoa butter was used. Analysis of commercial batches of 100 mg indometacin-polyethylene glycol... 

A transesterification reaction that blocks prostaglandin synthesis is responsible for aspirin s activity as an anti-inflammatory agent. Prostaglandins have several different biological functions, one of which is to stimulate... 

Tang, M., et al. Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. J. Pharmacol. Exp. Ther. 2006, 319, 1467-1476. 

Aspirin is an anti-infiammatory agent because it inhibits the conversion of arachidonic acid to prostagiandins by the transfer of its acetyi group (CH3CO-) to an OH group at the active site of an enzyme (Section 19.6). This reaction, caiied transesterification, resuits in the conversion of one ester to another by a nucieophiiic acyi substitution reaction. Draw a stepwise mechanism for the given transesterification. 

In the hody, aspirin (a relatively reactive phenyl alkanoate, see Prohlem 59) acts as an acetylating agent of the enzyme cyclooxygenase (COX). It does so by transesterification with the hydroxyl function of the amino acid serine of the polypeptide chain in the active site (see below). Inta-estingly, while sahcylic acid itself is also a COX inhibitor, it works by a different mechanism, namely, suppression of the genetic information that encodes the enzyme, thus attenuating its production. 

Figure 5.38 Transesterification resuiting in acetylation of paracetamol by aspirin.

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