German scientists use oxygen and light to synthesise anti-malaria drug
The simple method discovered by scientists at the Max Planck Institute could make it easier to produce arteminisin in large quantities
Scientists at the Max Planck Institute of Colloids and Interfaces in Potsdam and the Freie Universität Berlin have developed a simple process for the synthesis of artemisinin, which pharmaceutical companies could only obtain from plants up to now.
The chemists use a waste product from current artemisinin production as their starting substance, which can also be produced biotechnologically in yeast, and convert it into the active ingredient using a simple yet ingenious method.
Peter Seeberger, director at the Max Planck Institute of Colloids and Interfaces in Potsdam and Professor of Chemistry at the Freie Universität Berlin and his colleague François Lévesque, said they used artemisinic acid, a substance produced as a by-product from the isolation of artemisinin from sweet wormwood, which is produced in volumes 10 times greater than the active ingredient itself. Moreover, artemisinic acid can easily be produced in genetically modified yeast as it has a simpler structure.
‘We convert the artemisinic acid into artemisinin in a single step,’ said Seeberger. ‘And we have developed a simple apparatus for this process, which enables the production of large volumes of the substance under very controlled conditions.’
The only reaction sequence known up to now required several steps, following each of which the intermediate products had to be isolated – a method that was too expensive to offer as a viable alternative to the production of the drug from plants.
The simplification of artemisinin synthesis meant the chemists had to depart from the paths typically taken by industry up to now. The effect of the molecule, which not only targets malaria but possibly also other infections and even breast cancer, is due to, among other things, a very reactive chemical group formed by two neighbouring oxygen atoms – referred to as an endoperoxide.
Seeberger and Lévesque used photochemistry to incorporate this structural element into the artemisinic acid. Ultraviolet light converts oxygen into a form that can react with molecules to form peroxides.
‘Photochemistry is a simple and cost-effective method. However, the pharmaceutical industry has not used it to date because it was so difficult to control and implement on a large scale,’ explains Seeberger. In the large reaction vessels with which industrial manufacturers work, flashes of light do not penetrate deeply enough from outside and the reactive form of oxygen is not produced in sufficient volumes.
The scientists say they have resolved this problem by channelling the reaction mixture containing all of the ingredients through a thin tube that they have wrapped around a UV lamp. In this structure, the light penetrates the entire reaction medium and triggers the chemical conversion process with optimum efficiency.
‘The fact that we do not carry out the synthesis as a one-pot reaction in a single vessel, but in a continuous-flow reactor enables us to define the reaction conditions down to the last detail,’ explained Seeberger.
‘We assume that 800 of our simple photoreactors would suffice to cover the global requirement for artemisinin.’
The scientists estimates that the synthesis process could be ready for technical use in about six months.
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