Synthesis of 2-aryl-3-(2-cyanoethyl)aziridines and their chemical and enzymatic hydrolysis towards γ-lactams and γ-lactones

Abstract

Trans- and cis-2-aryl-3-(2-cyanoethyl)aziridines, prepared via alkylation of the corresponding 2-aryl-3-(tosyloxymethyl)aziridines with the sodium salt of trimethylsilylacetonitrile, were transformed into variable mixtures of 4-[aryl(alkylamino)methyl]butyrolactones and 5-[aryl(hydroxy)methyl]pyrrolidin-2-ones via KOH-mediated hydrolysis of the cyano group, followed by ring expansion. In addition, next to this chemical approach, enzymatic hydrolysis of the former aziridinyl nitriles by means of a nitrilase was performed as well, interestingly providing a selective route towards the above-mentioned functionalized γ-lactams.

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

“…the instability of the reactive four-membered ring under the above-mentioned conditions, required more mild -but still effective -procedures, we reverted to biocatalytic protocols for the hydrolysis of nitriles to carboxylic acids using isolated nitrilase enzymes as the hydrolyzing tools, as already applied successfully in previous work. 64,65 The repertoire of classical organic synthesis can indeed be signicantly enriched by including biochemical methods, and the interface between organic chemistry and biocatalysis is offering new strategies and perspectives as valuable alternatives. This can be attributed to the enantio-, stereoand regioselective, efficient and environmentally friendly catalysis applied by enzymes under mild reaction conditions, which ts perfectly in the framework of the integration of biocatalysis into the organic chemistry sector as an answer to the increasing demand for sustainable processes.…”

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“…The use of 2-aryl-3-(2-cyanoethyl)aziridines as substrates for nitrilase hydrolysis and the synthesis of g-lactams has been studied. 23 In contrast to standard chemical hydrolysis methods which gave mixtures of g-lactams and g-lactones, the use of nitrilase was highly selective for the preparation of g-lactams (Scheme 1). A one-pot, asymmetric synthesis of 1-arylethanols from styrenes has been achieved using a combination of a Wacker oxidation and an alcohol dehydrogenase reduction.…”

Chemoenzymatic Approach toward the Synthesis of 3-O-(α/β)-Glucosylated 3-Hydroxy-β-lactams

“…Yet, convinced by the assets of biocatalysis and its implementation in organic synthesis, as was also demonstrated by our preliminary studies on the chemoenzymatic syntheses of biologically relevant azaheterocyclic compounds, , the enzymatic glucosylation of chemically prepared cis -3-hydroxy-β-lactams 8 , without affecting the sensitive four-membered ring system, is envisioned in the current work. In fact, enzymatic glycosylation of 3-hydroxy-β-lactams as challenging substrates based on their rigidity and steric bulk, has never been described before.…”