Synthesis of alkyl derivatives of 3,7,10-trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane and evaluation of their biological activity

Abstract

Today 3,7,10-trioxo-2,4,6,8,9,11-hexaaaza[3.3.3]propellane (THAP) has not yet received widespread research attention due to the complexity of the synthesis. This work is devoted to the development of a method for the THAP derivatives synthesis, as well as to the study of their biological activity in comparison with alkyl- substituted glycolurils (subject of comparison). ТНАР was N-alkylated to furnish novel hexaalkyl derivatives of ТНАР with methyl, ethyl and propyl substituents. The conditions for obtaining the maximum yield of the target product were optimized on the base of methyl derivative. The reaction proceeded in DMSO/КОН at 75–80 ºC for 13 hours in a moderate yield of 56 %. The ethyl and propyl derivatives of ТНАР were synthesized under the same conditions. The biological activity of the obtained ТНАР alkyl derivatives and glycoluril alkyl derivatives was evaluated against Sporosarcina ureae, Bacillus pumilus, Salmonella typhimurium and Staphylococcus aureus bacteria and influenza A virus. All the samples were found to exhibit antibacterial activity against Staphylococcus aureus. It was shown that 2,4,6,8,9,11-hexapropyl-ТНАР, ditert- butyl-diphenyl-, di-tert-butyl-dibenzyl-, di-tert-butyl-dimethyl- and di-isopropyl-dibenzylglycoluril, have exhibited also toxicity to living cells besides antiviral activity.