Lactamomethyl derivatives of diphenols: synthesis, structure, and potential biological activity

Lactamomethylation of Phenols: Synthesis, In Silico Study of Reactivity and Possible Applications

“…The free energy ∆G values (E, a.u.) are shown for each particle.The same observations were made for catechol derivatives[20] (Scheme 5). Hydrogens in intermediate 11a forms strong hydrogen bonds with nearby oxygens.…”

“…The reagents and solvents were commercial products (Acros and Sigma-Aldrich). 1hydroxymethylpyrrolidin-2-one, 1-hydroxymethylazepan-2-one, 1-hydroxymethyl-4phenylpyrrolidin-2-one, used as the starting compounds were synthesized as described previously [19,20]. The synthesis of 2,4-di-tert-butylphenol and thymol derivatives have been also described previously [19].…”

“…As a result, we have successfully synthesized alkylphenols derivatives (of 2,4-di-tertbutylphenol and thymol) with the fragments of pyrrolidone, valerolactam, caprolactam and 4phenylpyrrolidone [19]. In addition, we have obtained similar compounds for polyphenolic compounds, such as catechol and hydroquinone [20], and resorcinol, pyrogallol and phenolic acids [21].…”

Remote Stereoelectronic Effects in Pyrrolidone- and Caprolactam-Substituted Phenols: Discrepancies in Antioxidant Properties Evaluated by Electrochemical Oxidation and H-Atom Transfer Reactivity

“…The toxicity of phenols is also an essential point 35 that can be potentially reduced by introducing a suitable pharmacophore. 36 Furthermore, several natural compounds, bearing both phenolic and heterocyclic moieties, when the latter belongs to lactams, are known for their biological activity. Thus, phenolic alkaloid oleracein E (Scheme 2), made via the fusion of tetrahydroisoquinoline and pyrrolidone fragments, demonstrates neuroprotective activity, 37 whereas brominated phenols with lactam substituents, extracted from algae, possess antifungal properties.…”

“…Despite the polyphenolic nature of these compounds, which should render them much more powerful antioxidants than mononuclear phenols in accordance with their redox properties, many flavonoids have relatively low bioavailability. − Hence, they are rapidly eliminated from the body and are relatively inactive as antioxidants. The toxicity of phenols is also an essential point that can be potentially reduced by introducing a suitable pharmacophore . Furthermore, several natural compounds, bearing both phenolic and heterocyclic moieties, when the latter belongs to lactams, are known for their biological activity.…”