Antimicrobial and antimycobacterial activities of aliphatic amines derived from vanillin

Abstract

Ten lipophilic amines were prepared from the reductive amination of vanillin and the corresponding primary amines using sodium borohydride in methanol. All compounds have been obtained elementally pure and an X-ray diffraction study on the 4-n-butylaniline derivative has confirmed the molecular structure. Whilst the overall antibiotic activity of the derivatives was low, some of these compounds, particularly the boronate ester 2-methoxy-4-((2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamino)methyl)phenol (7), showed a promising degree of antimycobacterial activity against Mycobacterium tuberculosis H37Ra, where activity seemed to vary by the position of the boron substitution on the aniline ring.

Boron-containing capsaicinoids

“…2 , 7a/b) demonstrated greater bioactivity. 35 In addition, our boron-containing capsaicinoid ( Fig. 2 , 7c) showed comparable bioactivity to our boron-omitted lipophilic substrates.…”

“…Chemistry Veratraldehyde (Scheme 1, 10) is the methylated derivative of vanillin and is used commercially as a fragrant and avourant, 39 as well as a starting material in the synthesis of some pharmaceuticals (e.g., Tiapamil, [40][41][42] and Verazide 43,44 ). In our previous study, 35 we chose vanillin as our starting aldehyde, but its use requires additional protection and deprotection steps for the compound to be suitable in the methodology employed. Consequently, we decided to use 10 as a replacement.…”

“…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).…”

“…To this extent, our initial study 35 focused on the synthesis and biological activity of select capsaicinoids that bear either a long aliphatic moiety or incorporate boron as a substituent on a phenyl group. These compounds were screened against Mycobacterium tuberculosis H37Ra, and it was found that substrates bearing long aliphatic chains ( Fig.…”