ABSTRACT
BACKGROUND: 2-Aminochromene derivatives display important pharmacological properties, including mainly antibiotic and anticancer activities. OBJECTIVE: The study aims to synthesize new chromene derivatives via a new approach using Grignard reagents, for the evaluation of their antibiotic and antifungal properties. METHOD: A series of novel 3-cyano-4-aminochromene derivatives bearing alkyl substituents at the 4-position was prepared for biological evaluation. RESULTS: These compounds were obtained by the addition of various Grignard reagents into Nethoxycarbonyl- 3-cyanoiminocoumarines in moderate to good yields (72-96%). The reaction is completely regioselective. The new chromene derivatives were screened for their in vitro antimicrobial activities against a panel of six bacterial and three fungal strains using agar dilution method. CONCLUSION: The antibacterial activity of the chromene derivatives was more pronounced on Gram-positive bacteria than on Gram-negative bacteria with a significant activity observed against Staphylococcus aureus. An interesting antifungal activity against Fusarium sp. and Fusarium oxysporum was also noticed.
Subject(s)
Carbamates/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Fusarium/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Spectrum Analysis/methods , Structure-Activity RelationshipABSTRACT
The successive addition of two different Grignard reagents to acyl cyanohydrins was performed with success by taking advantage of the low reactivity of alkynyl Grignard reagents. The experimental conditions were adjusted so that they were not reactive during the first addition step, but reactive only in the second one. The synthetic utility of the prepared compounds was validated by the preparation of chiral quaternary α-amino acids.
ABSTRACT
The double addition of Grignard (alkyl, aryl, alkenyl, alkynyl) reagents to acyl cyanohydrins was performed under unusually smooth conditions with a concomitant O-N acyl transfer, providing a very simple and general access to α,α,α-trisubstituted amides.