During a programme of work directed at developing a manufacturing route for SB 214857, Lotrafiban, the need arose to find methodology for efficiently destroying hydrogen peroxide in aqueous solutions of the penultimate intermediate, SB 270051.Whilst this was initially achieved using a chemical process, a biotransformation process has now been developed that utilises a polymer-supported catalase enzyme to remove peroxide from reaction mixtures. The biocatalytic approach provides an economic and environmentally friendly solution to peroxide removal when compared to the chemical process.
During the scale-up of a chemical process to produce phase II
supplies of the chiral compound Lotrafiban, partial racemisation occurred to produce drug substance of unacceptable chiral
purity. A new route capable of producing several hundred
kilograms of Lotrafiban of high chiral purity had to be rapidly
identified and scaled up. The strategy adopted was to employ
an enzymic resolution as the final step, thus introducing the
chirality under very mild conditions to prevent any racemisation. This was achieved using an immobilised form of the
Candida antarctica B lipase in water at 30 °C. The biotransformation was demonstrated to be a robust, reliable, and an
economic way to introduce the chirality into the Lotrafiban
molecule.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.