Highly efficient and enantioselective biotransformations of β-lactam carbonitriles and carboxamides and their synthetic applications

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

“…[59][60][61][62] Only two reports, however, describe the biocatalytic conversion of b-lactamcontaining nitriles. 49,58 In these studies, catalyzed by Rhodococcus erythropolis AJ270 cells containing nitrile hydratases and amidases, the rst set of enantiomers of racemic 3-nonsubstituted 4-cyano-and 4-cyanomethyl-b-lactams was converted toward the amides, while the others were fully hydrolyzed toward the carboxylic acids, which can be attributed to the high enantioselectivity exhibited by the amidases, in contrast to the lack of this stereocontrol in the case of nitrile hydratases. 63 In neither of these studies, however, the carboxylic acids were isolated.…”

“…55 In the next stage, the selective hydrolysis of the nitrile function within the synthesized (3R,4S)-3-alkoxy/aryloxy-4-cyanomethyl-b-lactams 11a-c was studied. Whereas the hydrolysis of nitriles containing a b-lactam moiety toward the corresponding amides has been reported a few times, both in a chemical 49,56,57 and in an enzymatic way, 49,58 reports describing the conversion of the latter nitriles toward carboxylic acids are rather scarce. In one of these examples, 4-(cyanomethyl) azetidin-2-one was chemically converted to the corresponding methyl ester rst, aer which alkaline hydrolysis gave rise to the acid.…”

Rhodococcus as a Versatile Biocatalyst in Organic Synthesis

“…Malononitriles are α, α-substituted dinitriles that form malonic diamides and malonic acid monoamides upon incubation with whole-cells of R. rhodochrous IFO 15564 [150]. Next to that, cyanohydrins (α-hydroxy nitriles) were also successfully hydrolyzed, leading to enantiopure α-hydroxy carboxylic acids like the pharmaceutical intermediate ( R )-chloromandelic acid on gram-scale [151] as was a large variety of aminonitriles ranging from α-aryl-, α-alkyl-substituted glycine nitriles [152,153,154] to aziridine-2-carbonitriles [155], azetidine-2-carbonitriles, and 4-oxoazetidine-2-carbonitriles [156,157].…”

Synthesis and Application of Enantioenriched Functionalized α-Tetrasubstituted α-Amino Acids from Biocatalytic Desymmetrization of Prochiral α-Aminomalonamides

“…A large number of amidases and microorganisms that contain amidases have been reported to date, and some of them have been studied extensively in the kinetic resolution of racemic amides for instance, has been shown to catalyze enantioselective biotransformation of a large number of structurally diverse racemic amides including amino-, hydroxy- and alkoxy-, alkenyl-, alkynyl-, allenyl-, and azido-bearing amides, cyclopropanecarboxamide, and various heterocyclic amides − to produce highly enantiopure carboxylic acid and amide products. Surprisingly, biocatalytic enantioselective desymmetrization of prochiral dicarboxamides remains largely unexplored.…”