op060003h_si_004.pdf (71.91 kB)
Selective Lipase-Catalysed Hydrolysis of a 1,2-Diester in the Development of a New Route to AZD2563 DSP
journal contribution
posted on 2006-05-19, 00:00 authored by Neil Barnwell, Lal Cheema, Janette Cherryman, Jérôme Dubiez, Garnet Howells, Andrew WellsDuring the development of a new route to AZD2563 DSP (DSP
= disodium phosphate), a selective enzyme-catalysed hydrolysis
of a 1,2-diester moiety to produce the secondary monoester was
developed. Apart from two esters, the target molecule also
contained three further functional groups prone to hydrolysis.
A major challenge to the chosen approach was the very facile
rearrangement of the desired secondary monoester product to
the undesired primary monoester. This rearrangement was
found to be catalysed by a wide range of chemicals and
inorganic materials usually considered as inert. The unique
selectivity and mild operating conditions of biocatalysis allowed
the desired reaction to be developed and successfully scaled up.