Synthesis of the pentacyclic core of lihouidine.

The pentacyclic base of the sponge-derived alkaloid lihouidine has been assembled from two quinoline fragments. The key step is a nitration-promoted cyclization to form the C-C bond between the two quinoline units.

Antibacterial Assessment of Heteroaryl, Vinyl, Benzyl, and Alkyl Tetrazole Compounds.

BACKGROUND: In previous reports, the antibacterial properties of certain tetrazole derivatives have been described. We have previously reported the antibacterial properties of aryl 1Htetrazole compounds. OBJECTIVE: To study the antibacterial activity of 5-substituted heteroaryl, vinyl, benzyl, and alkyl 1H-tetrazole derivatives. METHODS: The antibacterial properties of heteroaryl, vinyl, benzylic, and aliphatic tetrazole derivatives were investigated against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The activity was assessed by determining the minimum inhibitory concentration of these tetrazole derivatives and comparing them to the known antibiotics amoxicillin, trimethoprim and sulfamethoxazole. RESULTS: The tetrazole compounds were prepared utilizing cerium(III) chloride heptahydrate catalysis at 160 °C for 1-4 h in a microwave reactor using an aqueous solvent mixture. The most active derivatives exhibited minimum inhibitory concentration values between 125-250 µg/mL against Escherichia coli. More importantly, these compounds were considerably more active when used in combination with trimethoprim and a significant synergistic effect was observed (MIC = 0.98-7.81 µg/mL) against E. coli and S. aureus. CONCLUSION: The tetrazole derivatives were synthesized in high yield and short reaction times in water. Several of the tetrazole compounds showed a significant synergistic antibacterial effect when used with trimethoprim.

Antimicrobial Evaluation of 5-Substituted Aryl 1H-Tetrazoles.

BACKGROUND: Tetrazole derivatives such as 1-substituted dinitrobenzyl tetrazoles and their oxa and selanyl analogs have previously been studied against drug-susceptible and multidrug-resistant mycobacteria. In addition, other tetrazole derivatives have been shown to inhibit CTX-M class A b-lactamases. OBJECTIVE: To study the antibacterial activity of 5-substituted aryl 1H-tetrazole derivatives. METHODS: The antibacterial activity of several known 5-substituted aryl 1H-tetrazole derivatives was evaluated against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The activity was assessed by determining the minimum inhibitory concentration of these tetrazole derivatives and comparing them to the known antibiotics amoxicillin, trimethoprim and sulfamethoxazole. RESULTS: Some derivatives showed significant antibacterial activity with the most active derivatives exhibiting a minimum inhibitory concentration (MIC) of 125-250 mg/mL against Staphylococcus aureus and Escherichia coli. Using some of these tetrazole compounds in combination with trimethoprim led to a synergistic effect that gave MIC values ranging from 0.24-1.95 mg/mL against Escherichia coli and 3.91-31.3 mg/mL against Staphylococcus aureus. The tetrazole derivatives were prepared in an isopropanol/water mixture using microwave heating at 160 oC for 1 h. The cycloaddition between organonitriles and sodium azide was catalyzed by indium chloride. CONCLUSION: This study shows a significant synergistic effect between the tetrazole compounds tested and trimethoprim which could be used to potentially develop new antibacterial agents.