A sharper reaction

Drs Andreas Luxenburger (left) and Lawrence Harris have developed a novel process for aminohydroxylation that will be valuable for the pharmaceutical industry.

In 1975, Nobel Prize winner Professor K Barry Sharpless developed an osmium-catalysed reaction that in one step converts cheap hydrocarbons called alkenes into vicinal amino alcohols, important products in organic chemical synthesis.

Later, he found a way to make the reaction "asymmetric", meaning its products were chiral (i.e. left- or right-handed) and hence of great interest for the synthesis of new pharmaceuticals.

Unfortunately, despite being widely used in research and with a number of improvements reported, this reaction—known as aminohydroxylation—still has some serious limitations: irreproducibility, the requirement for use of an unstable oxidising reagent and added base, and the formation of undesired by-products.

This has limited the general applicability of the methodology by the pharmaceutical manufacturing industry.

GlycoSyn, IRL's pharmaceutical development and scale-up arm, offers for sale several high-value, biologically active research materials that include the vicinal amino alcohol functionality, especially allosamidin, an enzyme inhibitor that may have implications for the treatment of asthma.

GlycoSyn's synthesis of allosamidin utilised the best known Sharpless aminohydroxylation technology, but variable yields, approaching zero when the reaction was attempted at increased scale, were a major problem.

The breakthrough came when Drs Simon Mee, Andreas Luxenburger and Lawrence Harris from IRL designed novel reagents that turned the Sharpless aminohydroxylation reaction into a reliable process that could be operated at scale without loss of yield or the need to add an additional substance as a base.

They were just as good in the asymmetric version of the reaction, where there was no loss of regio- and stereo-selectivity, says Dr Richard Furneaux, head of IRL's world-renowned Carbohydrate Chemistry group.

"A further advantage is that the reaction conditions are compatible with base-sensitive functional groups, so that there is greater flexibility in the choice of protecting groups used during synthesis.

"These alkyl benzoyloxycarbamate reagents are crystalline, stable and easy to prepare on a kilogram scale.
"GlycoSyn is excited at the potential of this new discovery,” GlycoSyn General Manager Dr Paul Benjes says.

"We plan to offer aminohydroxylation as a service to our pharmaceutical industry clients, and make the new reagents available for purchase on a kilogram scale as well. 

"A provisional patent application has been filed, and we are willing to consider licensing arrangements that might assist greater uptake of the technology worldwide." 

To find out more about the technology, purchasing the reagents, hiring the service or licensing the technology, contact GlycoSyn account manager Dr Tony Davidson.