A nitrilase-mediated entry to 4-carboxymethyl-β-lactams from chemically prepared 4-(cyanomethyl)azetidin-2-ones

(3 R ,4 S )-3-Alkoxy/aryloxy-4-(cyanomethyl)azetidin-2-ones were efficiently prepared from readily available 1,2:5,6-di- O -isopropylidene- d -mannitol by means of a classical organic synthesis approach via 4-hydroxymethyl-β-lactams as key intermediates. The corresponding 4-carboxymethyl-β-lactams were subsequently obtained after selective hydrolysis of the nitrile functionality by means of a nitrilase enzyme without affecting the sensitive four-membered ring system, hence overcoming the difficulties associated with the chemical hydrolysis approach. Thus, the implementation of a biocatalytic step allows a convenient synthetic route to new 4-carboxymethyl-β-lactams as versatile building blocks for further elaboration. 4-(Cyanomethyl)azetidin-2-ones were efficiently prepared from 1,2:5,6-di- O -isopropylidene- d -mannitol, followed by a nitrilase-catalyzed hydrolysis to 4-carboxymethyl β-lactams without affecting the sensitive four-membered ring system.