Efficient synthesis of highly enantiopure β-lactam derivatives from biocatalytic transformations of amides and nitriles

Machine Learning Classification of One-Chiral-Center Organic Molecules According to Optical Rotation

“…Another outlier (7) was discovered among sesquiterpene natural products 8 and 9 in which the differences in the structures occur outside the fourth sphere of atoms from the chiral center (Figure ). , A similar situation occurs with compound 10 of the test set (Figure ), for which a negative value of the specific optical rotation was reported in methanol; the training set includes related compounds in which the methoxy group is replaced by fluorine or methyl and exhibit positive values of the optical rotation in the same solvent . A small change in the chemical structure may cause a shift in the optical rotatory dispersion (ORD) curve and the inversion of the sign of rotation at 589 nm.…”

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

“…microwave conditions), the reaction time., no substitution of either the mesyloxy or the tosyloxy group by cyanide could be achieved. Therefore, inspired by similar cases concerning 4-(mesyloxymethyl)azetidin-2-ones described in the literature, [49][50][51] an alternative approach was studied consisting of the Scheme 1 preliminary conversion toward more reactive 4-iodomethyl-blactams 10a-c as versatile intermediates, 52-54 as iodide is considered to be a very good leaving group combined with the expected decrease in steric hindrance during the substitution reactions as compared to sulfonyloxy leaving groups. 51 Both 4-mesyloxymethyl-and 4-tosyloxymethyl-b-lactams 8a,b and 9a-c were therefore converted into the corresponding iodides 10a-c by means of an excess of sodium iodide in acetone under reux (69-97%).…”

“…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.…”

“…[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.…”

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“…Wang and co-workers have examined the ability of a nitrile hydratase and an amidase from the microbial strain Rhodococcus erythropolis AJ270 to perform kinetic resolution of b-lactam derivatives. 28 While the nitrile hydratase resolved 4-cyanomethyl-b-lactams with low enantioselectivity, the use of the amidase from this organism for the resolution of 4-carbamoyl-b-lactams gave the corresponding products in excellent enantioselectivity (Scheme 5). The products of these transformations were shown to be useful synthetic intermediates for the generation of novel b-lactam fused heterocyclic compounds.…”