We're interested in the efficient synthesis of chiral small molecules. A major project in our lab is the inexpensive synthesis of enantiopure praziquantel, the drug used in the treatment of schistosomiasis (Bilharzia). This terrible disease affects nearly half a billion people worldwide. Praziquantel (PZQ) is being distributed on a huge scale by WHO/TDR and the Gates Foundation, administered by the Schistosomiasis Control Initiative. Praziquantel is on WHO's list of essential medicines (http://www.who.int/topics/essential_medicines/en/). Though it works well, PZQ is the only drug available for the treatment of schisto. There is much interest therefore in the discovery of alternatives before they are needed. We have demonstrated the solid phase synthesis of PZQ, and have made and tested some new analogues with variation in the aromatic ring, and are pursuing novel variants not covered in the original patent literature. We need to work out the mechanism of action of PZQ, which is still not known after more than 30 years of constant use!

PZQ is synthesised and administered as a racemate, but only one enantiomer is active. The other is associated with unpleasant side effects. To postpone the inevitable development of resistance, the dose needs to be increased. PZQ is already taken in large quantities, and tastes terrible, meaning that compliance issues are a big headache, particularly in the field. We are working towards an inexpensive, enantioselective synthesis. The unusual nature of this research problem is that the synthesis has to be very cheap, and therefore atom economical and sustainable. We are therefore taking an open source approach to this work (article 1 & article 2), and are coordinating the science on The Synaptic Leap website.

We're looking to extend the open source concept to other diseases, in particular the efficient synthesis of other small, chiral drugs.