Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam and the Freie Universität Berlin have developed a very simple process for the synthesis of artemisinin – the best anti-malaria drug – more economically and in sufficient volumes for all patients. This means that it will be possible to provide medication for the 225 million malaria patients in developing countries at an affordable price.

An Anopheles female mosquito that transmits malaria(© picture alliance/dpa Fotografia)Over one million people die of malaria each year because they do not have access to effective drugs.Millions, especially in the developing world, cannot afford the combination drug preparation, which consists mainly of artemisinin.

Moreover, the price for the medication varies, as this substance is isolated from sweet wormwood (Artemisia annua) which grows mainly in China and Vietnam, and varies seasonally in its availability.

Pharmaceutical companies could only obtain the drug from plants up to now. The chemists use a waste product from current artemisinin production as their starting substance. This substance can also be produced biotechnologically in yeast, which the scientists convert into the active ingredient using a simple yet very ingenious method.

This may be about to change. Peter H. 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 have discovered a very simple way of synthesising the artemisinin molecule, which is known as an anti-malaria drug from traditional Chinese medicine and has an extremely complex chemical structure. “The production of the drug is therefore no longer dependent on obtaining the active ingredient from plants,” says Peter Seeberger.

Synthesis from a by-product of artemisinin production

As a starting point, the chemists use artemisinic acid – a substance produced as a hitherto unused by-product from the isolation of artemisinin from sweet wormwood, which is produced in volumes ten times greater than the active ingredient itself. Moreover, artemisinic acid can easily be produced in genetically modified yeast as it has a much simpler structure. “We convert the artemisinic acid into artemisinin in a single step,” says Peter 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 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 – which chemists refer to as an endoperoxide. Peter Seeberger and François Lévesque use 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.

800 photoreactors should suffice to cover the global requirement for artemisinin

Dr. Peter H. Seeberger, Director at the Max Planck Institute of Colloids and Interfaces in Potsdam and Professor of Chemistry at the Freie Universität Berlin(© dpa)“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 Peter Seeberger.

“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,” explains Peter Seeberger.

After just four and a half minutes a solution flows out of the tube, in which 40 percent of the artemisinic acid has become artemisinin. “We assume that 800 of our simple photoreactors would suffice to cover the global requirement for artemisinin,” says Peter Seeberger. And it could all happen very quickly. Peter Seeberger estimates that the innovative synthesis process could be ready for technical use in a matter of six months. This would alleviate the global shortage of artemisinin and exert considerable downward pressure on the price of the associated drugs…….see        http://www.india.diplo.de/Vertretung/indien/en/__pr/Edu__Science__News/Malaria__drug.html

Max Planck Institute for Colloids and Interfaces