Question

Oxycodone is an opioid analgesic used for the treatment of moderate to severe pain. It is approximately twice as potent as an equivalent dose of morphine when taken orally. It is usually taken every 12 hours. A growing number of reports indicate that oxycodone is being abused, resulting in overdoses and death.

As the name indicates, oxycodone contains a ketone functional group (in addition to other functional groups). The structure of oxycodone is shown below. Considering the ketone (or one of the ether functional groups), explain why synthesis of this compound is low yielding.

Answer 1

Synthesis of Oxycodone in lower yield

The overall synthesis of Oxycodone an opiodic analgesic is formed from the thebaine of codeine. Thebaine is oxidised to 14-hydroxycodeinone. It is attained with m-chloperoxybenzoic acid in acetic acid/trifluoro acetic acid. Oxycodone is obained by the catalytic hydrogenation of C=C in 14- hydroxycodeinone.

Semisynthesis

It is the method in which the chemical species separated from the naturally occuring sources.

The main reason for the minimal yield of the product is due to the semisynthesis process. Basically Oxycodone is a semisynthetic opioid which is obtained from the opiate alkaloid thebaine.

The lesser yield of oxycodone from thebaine is because of the reaction route and the choice of the N-demthylation Oxidation of the atropine which is alkaline in nature with Hydrogen peroxide. In this reaction Fe-III TAML is used as a catalyst. By using oxidants such as tert-butyl or cumene hydroperoxide, will move the reaction selectivity towards oxidation of N-methyl which balances with aqueous Hydrogen peroxide. Inadequate inorganic oxidants are observed. Catalysation reaction is carried out by the catalyst Fe III - TAML in N-demethylation of the opiate alkaloid such as thebaine and oxycodone with aqueous Hydrogen peroxide in larger alteration ability but with lower selectivity when matching with atropine. This leads to a lower yield of oxycodone. But it is very pure and there is a reaction shifting.