Photodegradable antimicrobial agents − synthesis, photodegradation, and biological evaluation

Abstract

The synthesis of several new compounds containing an ethanolamine moiety are reported, of which two exhibit promising antimicrobial activity (at the 6 μM level).

Photodegradable Antimicrobial Agents: Synthesis and Mechanism of Degradation

“…To make a range of compounds, some key building blocks, one aniline and three epoxides, were prepared as summarized in Scheme 5 . 32 Aniline 10 was synthesized from the corresponding trihaloaniline by performing acetylation followed by nitration and acidic hydrolysis, which furnished 10 in 61% overall yield. Two of the epoxides were prepared from 1-bromo-2,6-difluorobenzene.…”

“…As already reported, ethanolamine derivatives 14a – 14d have been screened against selected Gram-positive and Gram-negative bacteria, including Escherichia faecalis , E. coli , Pseudomonas aeruginosa , Staphylococcus aureus , S. agalactiae , and S. epidermidis , and showed promising antibacterial activity with a minimum inhibitory concentration (MIC) as low as 6.3 μM in the best cases ( 14a and 14d ) ( Scheme 6 ). 32 It was therefore very disappointing when all of the remaining seven analogues were totally inactive (MIC > 100 μM). More compounds have to be prepared and tested before the reason for this difference can be elucidated, but four noteworthy trends have been observed.…”

“…With the photodecomposition process essentially proved, we started the search for biologically active analogues to 5a by reacting benzyloxirane derivatives with anilines containing aryl groups that have been found in other molecules showing biological activity. To make a range of compounds, some key building blocks, one aniline and three epoxides, were prepared as summarized in Scheme . Aniline 10 was synthesized from the corresponding trihaloaniline by performing acetylation followed by nitration and acidic hydrolysis, which furnished 10 in 61% overall yield.…”

“…To make a range of compounds, some key building blocks, one aniline and three epoxides, were prepared as summarized in Scheme 5. 32 Aniline 10 was synthesized from the corresponding trihaloaniline by performing acetylation followed by nitration and acidic hydrolysis, which furnished 10 With these building blocks at hand, a number of target molecules could be synthesized using a Lewis acid-promoted epoxide ring-opening reaction in a 5 M LPDE solution, to which the anilines and epoxides were added (Scheme 6). No product was obtained in better than 50% yield, conceivably because the anilines react sluggishly because they are rather poor nucleophiles due to the electron-withdrawing substituents.…”

“…We recently communicated the synthesis and biological evaluation of four antimicrobial agents based on a new scaffold, which facilitated light-induced fragmentation leading to the formation of inactive and nontoxic compounds. 32 This chemistry opens up the possibility to prepare new antimicrobial agents that decompose in the environment after release. Here, a full account of the synthetic work and studies of the photodecomposition mechanisms is presented.…”