Application of biocatalysis towards asymmetric reduction and hydrolytic desymmetrisation in the synthesis of a β-3 receptor agonist

Green Chemistry Pub Date: 2011-09-01 DOI: 10.1039/C1GC15694B

Abstract

Chemoenzymatic syntheses of two key intermediates in the preparation of a potent β-3 receptor agonist 1 are described. A lipase-catalysed hydrolytic desymmetrisation is employed in a new synthesis of intermediate 7, which avoids the use of alkyl-tin reagents. A second biotransformation delivers chiral chlorohydrin 5 from its parent ketone in greater enantiomeric excess than the previously-described Noyori-reduction process. A brief discussion of the enantioselectivity of a set of single-point mutants of Sporobolomyces salmonicoloraldehyde reductase in this bioreduction is also presented.

Graphical abstract: Application of biocatalysis towards asymmetric reduction and hydrolytic desymmetrisation in the synthesis of a β-3 receptor agonist
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