Antibacterial N-[.omega.,.omega.'-bis(alicyclic and aryl)-sec-alkyl]poly(methylenetriamine and -tetramine) hydrochloride salts

Abstract

A series of antibacterial N-(omega, omega'-(cycloalkyl, bicyclo[2.2.1]heptyl, and alkyl-substituted phenyl)-sec-alkyl]poly(methylene)triamine and -tetramine hydrochloride salts were synthesized in an effort to develop efficient, nonsystemic inhibitors, particularly for Pseudomonas aeruginosa. In the 1,5,9-triazanonane group, 3 of 16 compounds were effective at 8--10 micrograms/mL against pseudomonads. Efficiency appeared more dependent upon lipophilicity of the nitrogen substituent than other characteristics represented by the three types of rings. A parabolic relationship was observed for the entire set between the hydrophobic parameter, pi, of the lipoidal moiety and minimal inhibitory concentration. One of 16 tetramines, 1-[1,5-bis(3,3-dimethyl-2-norbornyl)-3-pentyl]-1,5,9,13-tetraazatridecane tetrahydrochloride (26f), ranked similarly. An additional two compounds in each series were superior to several commercial cationic detergents in the control of the Gram-negative bacteria. None was inhibitory at up to 200 micrograms/mL for Proteus vulgaris.

New Synthesis of Propargylic Amines from 2-(Bromomethyl)aziridines. Intermediacy of 3-Bromoazetidinium Salts

“…66,67 The presence of an aminomethyl functionality in the vinyl bromides 6 allows a new approach toward R-(aminomethyl)-substituted R,β-unsaturated ketones, which have an interest as antimicrobial agents and for the treatment of pain, fever, and inflammation. 68,69 To reach this objective, N,N-dibenzyl-N-(2-bromo-2-propenyl)amine 6a was transformed in the corresponding trimethylstannyl derivative 18 by reaction with bis(trimethyltin) in the presence of a catalytic amount of Hu ¨nig's base and tetrakis(triphenylphosphine)palladium in benzene at 80 °C for 15 h. 66,67 ). This reaction proves that the conditions for a Stille coupling can be successfully applied for nitrogen-containing vinyl bromides, pointing to the conclusion that vinyl bromides 6 can be applied as useful synthetic intermediates in different synthetic pathways.…”

“…Vinyl bromides are known to be good substrates for Stille coupling reactions. , The presence of an aminomethyl functionality in the vinyl bromides 6 allows a new approach toward α -(aminomethyl)-substituted α , β -unsaturated ketones, which have an interest as antimicrobial agents and for the treatment of pain, fever, and inflammation. , To reach this objective, N , N -dibenzyl- N -(2-bromo-2-propenyl)amine 6a was transformed in the corresponding trimethylstannyl derivative 18 by reaction with bis(trimethyltin) in the presence of a catalytic amount of Hünig's base and tetrakis(triphenylphosphine)palladium in benzene at 80 °C for 15 h. , This stannane 18 was then further reacted with 2-methylpropanoyl chloride in a palladium-based Stille coupling reaction with Hünig's base and tris(dibenzylideneacetone)dipalladium in benzene at room temperature for 2 h, , resulting in 2-[(dibenzylamino)methyl]-4-methyl-1-penten-3-one 19 in 88% yield (Scheme ). This reaction proves that the conditions for a Stille coupling can be successfully applied for nitrogen-containing vinyl bromides, pointing to the conclusion that vinyl bromides 6 can be applied as useful synthetic intermediates in different synthetic pathways.…”