Preliminary investigations into the synthesis and antimicrobial activities of boron-containing capsaicinoids

Abstract

This preliminary study reports on the synthesis of two new boron-capsaicin derivatives containing either a short or long chain aliphatic tail group using an iridium catalyzed hydroboration reaction with pinacolborane. The boronate ester groups reside on the terminal position of the tail group and are necessary for the bioactivity of these compounds. Indeed, both compounds showed considerable activity against two Gram-positive bacteria, including Vancomycin-resistant Enterococcus. Vancomycin is considered the last resort medication for the treatment of septicemia, and new antibacterial agents that can treat sepsis are of paramount importance. The more lipophilic boron compound with the longer aliphatic chain also showed antifungal activity against Saccharomyces cerevisiae.

Boron-containing capsaicinoids

“…Our desboro-aryl amine substrates either were unsubstituted (16) or bore aliphatic chains (17,18). We have previously found that increasing the length of aliphatic substituents on our boron-containing capsaicinoids provided greater antimicrobial activity, 36 and so functionalization at this position provided an opportunity to further tune the lipophilicity of the capsaicinoid. Amines 16-18 were isolated in modest to good yield.…”

“…*Data collected in previous study, inhibition above 400 μM was considered inactive; activity against S. warneri was not previously studied. 36 …”

“…2 , 8a/b). 36 Both compounds demonstrated antibacterial activity against vancomycin-resistant Enterococcus , and the more lipophilic compound ( Fig. 2 , 8b) displayed broader antimicrobial activity.…”

“…12,13 Our group has a long-standing interest in developing bioactive organoboron compounds, including boroncontaining capsaicinoids. 35,36 Capsaicin (6, Fig. 2) is the colourless, hydrophobic, crystalline compound 37 that is responsible for the characteristic spicy "heat" avouring of the chili fruits of the Capsicum genus.…”

“…2, 8b) displayed broader antimicrobial activity. 36 Based on the results of both studies, 35,36 we have chosen to expand the substrate scope to include boron-containing capsaicinoids featuring tertiary amides that bear a long aliphatic tail (Fig. 2, 9).…”