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In this study, the preparation of 4-imidoyl-, 4-oxiranyl-, and 4-propargyloxyphenyl-substituted beta-lactams as versatile building blocks in heterocyclic chemistry was realized. Efforts were made to deploy these polyvalent compounds for ensuing cyclization reactions en route to new bi- or polycyclic frameworks, which, in the case of a 3-chloro-4-propargyloxyphenyl-beta-lactam substrate, enabled the preparation of an unprecedented beta-lactam-fused benzotriazolo-oxazocane scaffold. The chemical structure of the latter polyheterocycle was unequivocally secured by means of X-ray analysis.

The reactivity of 3-oxo-β-lactams with respect to primary amines was investigated in depth. Depending on the specific azetidin-2-one C4 substituent, this reaction was shown to selectively produce 3-imino-β-lactams (through dehydration), α-aminoamides (through CO elimination), or ethanediamides (through an unprecedented C3-C4 ring opening). In addition to the experimental results, the mechanisms and factors governing these peculiar transformations were also examined and elucidated by means of DFT calculations.

Within heterocyclic chemistry, β-lactams comprise an extraordinary class of strained compounds, recognized for their biological importance as potent antibiotics and their chemical value as flexible building blocks for the construction of diverse nitrogen-containing structures. Among the synthetic routes available to access this interesting scaffold, the carbonylation of aziridines, in which carbon monoxide is inserted into one of the ring carbon–nitrogen bonds, is praised for its efficiency and remarkable regio- and stereoselectivity. This review provides a comprehensive overview of aziridine-to-azetidin-2-one carbonylation studies. The protocols are categorized according to the different transition metals (i.e. rhodium, palladium, nickel, iron, and cobalt) that have been employed (in a catalytic or stoichiometric amount) to effect this transformation.

(3R, 4S)-3-Alkoxy/aryloxy-4-(cyanomethyl) azetidin-2-ones were efficiently prepared from readily available 1,2: 5,6-di-D-isopropylidene-D-mannitol by means of a classical organic synthesis approach via 4-hydroxymethyl-beta-lactams as key intermediates. The corresponding 4-carboxymethyl-beta-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-beta-lactams as versatile building blocks for further elaboration.

Trimethylene-tethered thymine-beta-lactam and thyminebis-beta-lactam chimeras were prepared as novel classes of hybrid systems through selective mono-or bis-N-alkylation of thymine with cis-1-(3-bromopropyl)-beta-lactams. In addition, acidic methanolysis of the beta-lactam nucleus in these systems provided an entry into the class of thymine-beta-amino ester hybrids. A selection of the newly synthesized hybrid compounds was assessed for their antiviral activity, cytotoxicity, and cytostatic activity, revealing a significant cytostatic effect of one of the derivatives against murine leukemia and human T-lymphocyte tumor cells.