ABSTRACT
Preliminary differentiating screening of the antibacterial and antifungal activity of a series of diastereomeric cis/trans-3-aryl(heteroaryl)-3,4-dihydroisocoumarin-4-carboxylic acids (3a-i) was performed by the agar diffusion method against twelve microorganism strains of different taxonomic groups. S. aureus and A. niger were the most sensitive strains to the antibiotic effect of the tested compounds, both inhibited by 10 of 12 compounds. The most potent antibacterial agent was cis-3-phenyl-3,4-dihydroisocoumarin-4-carboxylic acid (cis-3a), exhibiting activity against all seven bacterial test strains.
Subject(s)
Anti-Bacterial Agents/chemistry , Carboxylic Acids/chemistry , Hydrazones/chemistry , Quinolones/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Bacteria/drug effects , Carboxylic Acids/isolation & purification , Carboxylic Acids/pharmacology , Coumarins/chemistry , Coumarins/isolation & purification , Coumarins/pharmacology , Fungi/drug effects , Hydrazones/isolation & purification , Hydrazones/pharmacology , Microbial Sensitivity Tests , Penicillin G/pharmacology , Quinolones/isolation & purification , Quinolones/pharmacology , StereoisomerismABSTRACT
The reaction of homophthalic anhydride and N-(furan-2-yl-methylidene)- benzylamine in different solvents and varying temperatures was studied in detail. Mixtures of the expected trans- and cis-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acids trans-5 and cis-5, along with by-products 6 and 7 were obtained in dichloroethane or benzene. In pyridine, used for the first time, the reaction became completely diastereoselective, giving only the trans isomer. The carboxylic acid group of trans-5 was transformed in four steps into cyclic aminomethyl groups which yielded various new tetrahydroisoquinolinones trans- 11a-g, incorporating both a known fragment of pharmacological interest and various pharmacophoric substituents.
