RESUMO
The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1-7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.
Assuntos
Anti-Inflamatórios , Inibidores de Glicosídeo Hidrolases , Lactamas , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Lactamas/química , Lactamas/farmacologia , Animais , alfa-Glucosidases/metabolismo , Simulação de Acoplamento Molecular , Camundongos , Relação Estrutura-Atividade , Simulação por Computador , Edema/tratamento farmacológico , Edema/induzido quimicamente , Estrutura MolecularRESUMO
Practical and convenient method for the synthesis of novel phosphonopeptides 8a-h and 10a-f incorporating the quaternary α-aminophosphonate 6 is reported. The target compounds were prepared in moderate to good yield based on the preparation of the quaternary α-aminophosphonate 6 followed by the formation of the α-bromoamide 7 and subsequent nucleophilic substitution reaction with several amines or by peptide bond formation with several amino acids and with the quaternary α-aminophosphonate 6, using isobutyl chloroformate as activating agent under racemization-free condition.
Assuntos
Ácidos Aminoisobutíricos/química , Glicopeptídeos/síntese química , Organofosfonatos/síntese química , Acilação , Catálise , Formiatos/química , Hidrogenação , Hidrólise , Solventes/químicaRESUMO
An efficient synthesis of enantiomerically-pure ß-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of ß-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the reduction of the γ-nitroester in the presence of Raney nickel and the subsequent saponification/decarboxylation reaction. The utility of this methodology was highlighted by the preparation of enantiomerically-pure (R)- and (S)-Baclofen hydrochloride.
Assuntos
Baclofeno/síntese química , Lactamas/síntese química , Naproxeno/química , Catálise , EstereoisomerismoRESUMO
Synthesis and structural characterization of 1,4,2-oxazaphosphepines is described. The 1,4,2-oxazaphosphepines were obtained from reaction of chiral 1,3-benzoxazines with dichlorophenylphosphine or triethyl phosphite. The configuration of some of these compounds was stablished by X-ray analysis.
Assuntos
Fenóis/química , Fenóis/síntese química , EstereoisomerismoRESUMO
We describe a protocol developed for the preparation of ß-enaminoketones derived from 1,3-cyclohexanediones, and their subsequent reduction by sodium in THF-isopropyl alcohol to afford cis- and trans-3-aminocyclohexanols.