Callistemenonone A, a novel dearomatic dibenzofuran-type acylphloroglucinol with antimicrobial activity from Callistemon viminalis

Abstract

A new acylphloroglucinol with a novel architecture including an unprecedented dearomatic dibenzofuran core, named callistemenonone A (1), was isolated from the leaves of Callistemon viminalis (Myrtaceae). The structure was fully characterized on the basis of extensive spectroscopic analysis, including UV, HRESIMS, as well as 1D and 2D NMR spectral data (HSQC, HMBC, and ROESY). The deduced structure represents the first example of a natural dibenzofuran with two phenyl moieties coupling through tertiary hydroxy and ketal carbons. A plausible biogenetic pathway involving oxidative coupling and dearomatization as key steps is proposed to account for the biosynthesis of this novel class of dibenzofuran. Moreover, antimicrobial assays, in conjunction with the time-killing and biophysical studies, revealed that 1 exerted potent bactericidal activity against a panel of methicillin resistant pathogenic microbes with a unique mechanism.

Callistemonols A and B, Potent Antimicrobial Acylphloroglucinol Derivatives with Unusual Carbon Skeletons from Callistemon viminalis

“…Based on the fact that numerous species in the Myrtaceae family exploit an antibiotic advantage by targeting the bacterial membrane, , comprehensive investigations were conducted to further understand the antimicrobial mechanism of 1 and 2 against clinical MRSA (JCSC 4744).…”

“…The MIC and MBC evaluations, a time–killing study, a cytoplasmic membrane depolarization experiment, a SYTOX green assay, and scanning electron microscopy studies on compounds 1 and 2 were carried out according to the standard methods. − Detailed procedures are described in the Supporting Information.…”

Phloroglucinol and Its Derivatives: Antimicrobial Properties toward Microbial Pathogens

“…The combination of callistemenonone A and melittin (a small peptide from bee venom) has been shown to have a synergistic effect against MRSA; however, the effect was minor. 58 Similarly, Lee et al 133 reported synergistic killing of methicillin-sensitive and methicillin-resistant S. aureus when dieckol was combined with β-lactams such as ampicillin or penicillin. Another compound, eckol, found in ethyl acetate extracts of Ecklonia cava, when combined with ampicillin, has a synergistic impact against S. aureus and an additive effect against Salmonella Typhimurium.…”

Recent advances in the synthesis of natural products containing the phloroglucinol motif

“…Among them, oligomerization of acylphloroglucinol leads to dimeric or trimeric phloroglucinol compounds. 14,15 It could also be conjugated with terpene units through hetero- or carbo-[4 + 2] or [3 + 2] cyclization to afford acylphloroglucinol–terpenes. 16,17 Polycyclic polyprenylated acylphloroglucinols (PPAPs) are generally biosynthesized from C -cyclization of prenylated acylphloroglucinols.…”