Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

Abstract

SummaryA chemical library of carboxamide-substituted tetramates designed by analogy with antibacterial natural products, a method for their rapid construction, and the evaluation of their antibacterial activity is reported.

Chemoselective Formation and Reaction of Densely Functionalised Bicyclic Tetramic Acids and Their Biological Activity

“…This assignment was confirmed from a 1 H– 13 C NOE experiment of compound 11a in C 6 D 6 (Supporting Information). In contrast, carboxamide‐ and alkoxy‐carbonyl tetramic acids exist as the endo ‐enol form, reflecting their differing capacity for stabilising resonance …”

“…In conclusion, a fully chemoselective Grignard displacement of Weinreb amides 7a-c has enabled the preparation of tetramic acids substituted with a range of side chain acyl groups; this alternative strategy to the classical acylation approach [7,12] offers a solution to the recently highlighted difficulty of the introduction of unsaturated side chains in such systems, [24] and neatly complements the work of Schobert which has demonstrated the suitability of Lacey-Dieckman cyclisation in highly sensitive substrates. [25] Some of these analogues had potent and selective activity against Gram-positive bacteria, and one is a first-in-class proteasome inhibitor.…”

“…In contrast, carboxamide-and alkoxy-carbonyl tetramic acids exist as the endo-enol form, reflecting their differing capacity for stabilising resonance. [12] Purification of acyl-tetramic acids by column chromatography has been reported to be difficult, and this is believed to be due to the pronounced tendency of these compounds for chelation with metals. [1c,13] In the work reported here-in, all acylated analogues gave broad NMR signals after silica gel purification, and needed to be washed with 2 M HCl to obtain metal-free samples with well-resolved NMR spectra ( Figure 2).…”

Evidence of Biocontrol Activity of Bioinoculants Against a Human Pathogen, Listeria monocytogenes

“…Several compounds containing pyran rings have been tested for their microbiocide properties (Rajan et al, 2017) and derivatives of 2H-pyran (thiourea and benzene sulfonylurea) possess antimicrobial activities (Faidallah et al, 2011). Carboxamides are not only being used as site-specific fungicides (Jangir et al, 2018) but have also been shown to possess antibacterial properties (Jeong and Moloney, 2013). Hence, it suggests that at least part of the inhibitory effects caused by these bioinoculants could be attributed to antibiosis triggered by the release of bioactive compounds during root colonization.…”

Identification of Chemical Compounds That Inhibit the Function of Glutamyl-tRNA Synthetase from Pseudomonas aeruginosa

“…24 Also, the carboxamide derivatives of tetramic acids based on antibacterial natural products have been shown to have bioactivity against various Gram-positive bacteria and also the Gram-negative organism H. influenzae . 25 Finally, using molecular hybridization, a series of carboxamide derivatives were synthesized and shown to be active against Mycobacterium tuberculosis (MTB). 26 These results, along with the activity of BT_03F04 observed against Gram-positive pathogens, indicate that further evaluation of a carboxamide-based lead series based on this compound may be advantageous.…”