University of York discovery: efficient method to produce pharmaceuticals

A PhD student at York’s Chemistry department has developed a new drug synthesis method that could widen the repertoire of drugs available to treat many common ailments.url

Many of us would have never heard of piperazines. However, they are among the most common chemical structures found in modern-day drug compounds. Piperazine is an organic compound consisting of a six membered carbon ring structure containing two nitrogen atoms at opposite positions.

A list of piperazine derivative used as drug is extensive. From the mind altering recreational drugs, antidepressants and antipsychotics. To physiological functions as anti-histamines, that are used to reduce inflammation, Citizirine, used to treat hay fever and Indinavir, one of the first antiretroviral therapies. This shows how high demand for this single compound must be.

Image: Melanie Tata

Image: Melanie Tata

However, it is particularly challenging to synthesize in certain forms. This limits piperazines’ potential uses in pharmaceuticals. It is extremely difficult to attach molecules to the carbon backbone ring. This limits modifications to the two nitrogen atoms.

James Firth, a PhD student in York’s Chemistry department has managed to develop a new method for functionalization of the piperazine structures so that they can be chemically modified more easily. The project involved a complex technique in organic chemistry called organolithium chemistry. The chemical nature of organolithium makes it very good at invading particular sites on other molecules allowing for synthesis of a new compound. This reaction pathway for the formation of modified piperazines was studied in depth using infra-red spectroscopy. Infra-red spectroscopy is used to identify different structural states as functional groups attached to a molecule produce characteristic bands of absorbance.

Professor Peter O’Brien, supervisor of James Firth’s project praises his ‘tenacity and creativity’ in contributing to the development of a new practical synthetic method for piperazines. This discovery opens the door to development of more pharmaceutical compounds derived from this already widely used molecule.