Exploration of aziridine- and β-lactam-based hybrids as both bioactive substances and synthetic intermediates in medicinal chemistry

Enantioselective cis-β-lactam synthesis by intramolecular C–H functionalization from enoldiazoacetamides and derivative donor–acceptor cyclopropenes

“…The importance of β-lactam compounds (2-azetidinones) in biology and medicine is undisputed since the discovery of the antibiotic activity of the bicyclic penicillin in 1928, 1 , 2 and monocyclic β-lactams that include the plasma cholesterol-lowering Ezetimibe 3 also show biological activity. 4 Considerable effort has been focused on chemical catalysis for the construction of β-lactams, including those through catalytic intramolecular amide N–H insertion reactions of diazo compounds, 5 and asymmetric synthesis has been a primary focus. 2 , 6 However, the same C–H functionalization methodology of diazo compounds that has provided exceptional selectivities in intermolecular reactions 7 and intramolecular syntheses of γ-lactones and γ-lactams 8 has been limited in efforts to synthesize β-lactams.…”

Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening

“…Treatment of 3 with Schiff bases 4a-j in the presence of equimolar amounts of triethylamine and p-toluenesulfonyl chloride produced the cis-β-lactams 5a-j in isolated yields varying from 68-80% after column chromatography. Structures were established on the basis of their IR, 1 H NMR, 13 C NMR spectral data and elemental analysis (see supplementary material). The IR spectra of 5b showed absorption band at υ 1759 cm -1 for the βlactam carbonyl group and absorption band at υ 1689 cm -1 for the aldehyde carbonyl group.…”

“…Electronic Supplementary Information (ESI) available: Spectra for new compounds (IR, 1 H NMR, 13 C NMR spectral data), elemental analysis, molecular docking studies data, crystallographic data and structure determination and General experimental methods.…”

“…The discovery and clinical development of β-lactam antibiotics remains one of the major advances in modern medicine [12]. The commonly used bicyclic β-lactam antibiotics such as the penicillins and cephalosporins prevent bacterial transpeptidases from crosslinking the polysaccharide cell wall [13]. More recently, functionalized monocyclic β-lactams have been developed having a host of other pharmaceutical capabilities, such as anti-HIV [14], antifungal [15], anticancer [16,17] and antimalarial [18] (Figure 3), anti-inflammatory, or analgesic activities [19].…”

Synthetic Approaches to Small- and Medium-Size Aza-Heterocycles in Aqueous Media

“…Aziridines are the smallest possible aza-heterocycles and well known to organic chemists for their tremendous potential in the design of organic synthesis and medicinal chemistry [4][5][6][7]. Aziridines are highly reactive compounds-still several natural products are found to bear such skeleton.…”