Rhodium catalysts speed up drug synthesis

By Huw Kidwell

- Last updated on GMT

Related tags: Enantiomer, Attention-deficit hyperactivity disorder, Chemical reaction

In the world of chemistry the majority of reactions are well known
and have been around for a very long time producing similar
compounds. It is not very often that a completely new reaction
methodology comes along which can turn something like chiral
chemistry on its head. However this is the case with a series of
rhodium (II) based chiral catalysts developed by US researchers.

The catalysts mediate in the insertion of carbenes and nitrenes to produce chiral compounds in fewer steps than ever before, with exceptional enantioselectivity, according to the developers. The team, from the University at Buffalo, the State University of New York, US, and led by Professor Huw M.L. Davies says the methods have become so good the catalysts are now being commercialised by start-up company Dirhodium Technologies. The company has fine tuned the expertise to produce the catalysts in kilogram quantities for chemical companies such as Strem and Aldrich to market to pharmaceutical companies. Expensive​ Rhodium is actually ten times more expensive than gold but the catalysts are becoming more and more sought after and Dirhodium Technologies is a success story, according to Davies. He told in-PharmaTechnologist.com: "When we first started producing the catalysts we would make 25 grams, with 20 grams for ourselves and five grams for the chemical companies but within six months they were asking for one kilogram.​" "There is at least one pharmaceutical company using our catalysts for the synthesis of a drug about to go into clinical trials​," added Davies. "It is important because what we have is a new strategy for synthesis with new reactions that allow asymmetric functionalisation in previously simple molecules using carbenes with rhodium (II) in the presence of other functional groups... so what we have is a new way of producing many complex molecules.​" The methodology will also produce new drug candidates from simple molecules in few steps and more importantly in a single enantiomer (chiral form), which is so important for pharmaceuticals as different enantiomers can have entirely different biological effects in the body (some harmful such as in the well known case of thalidomide, which was marketed as a racemate). New Ritalin ​ One excellent example of the use of these catalysts is in the synthesis of Ritalin (methylphenidate), a drug developed by Novartis for the treatment of attention deficit hyperactivity disorder (ADHD). The drug is sold as a racemate (50/50 chiral mixture) and is synthesised conventionally by using eight to nine steps. Each step reduces the yield of the reaction (so the more steps the less you get back). In the chiral catalyst mediated reaction the drug can be synthesised in only two steps in the required chiral form. Obviously a scenario such as this is valuable to a pharmaceutical company as it would make synthesis easier and even though the catalyst is expensive the economics of the overall process would result in money being saved (with only a single gram of catalyst tens of kilograms of compound can be produced). The catalysts can also produce some surprising and exciting new structures to broaden the field of drug discovery.

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