Recent Advances in the Exploitation of Kojic Acid in Multicomponent Reactions

Kojic acid, one of the most widespread 3-hydroxypyran-4-one derivatives, displays a wide range of biological activities and found application in food as well as cosmetics industry. The synthesis of kojic acid derivatives has provoked great interest as an easily available and biologically active precursor among organic and medicinal researchers. Multicomponent reactions, involving three or more reactants in one-pot thereby resulting in a structure with functional diversity are efficient methods for the promotion of green chemistry in the context of modern drug discovery. They offer several advantages over conventional stepwise protocols like simplicity, efficiency, selectivity, convergence and atom economy. This review aims to highlight the versatility of kojic acid as an important synthon in multicomponent reactions for the construction of various biologically relevant compounds such as pyrano[3,2‐ b]chromenediones, pyrano[3,2-b]pyrans, pyrano[2′,3′:5,6]pyrano[2,3‑b]pyridines, spiro[indoline-3,4’-pyrano[3, 2-b]pyrans, 2-substituted kojic acid conjugates, etc.

Simultaneously Quantitative Analysis of Naringin and Its Major Human Gut Microbial Metabolites Naringenin and 3-(4′-Hydroxyphenyl) Propanoic Acid via Stable Isotope Deuterium-Labeling Coupled with RRLC-MS/MS Method

Widespread in citrus fruits, naringin, a natural 2,3-dihydroflavonoid, is of particular interest to scientists and has a broad range of beneficial bioactivities to health. Orally administered naringin remains in the gut tract for a relatively long time because of its low bioavailability. Under the metabolism mediated by human gut microbiota, naringin could be an active precursor for derived metabolites to play important physiological roles. However, naringin and its metabolites are hard to accurately quantify due to severe endogenic interference. In this study, an analytical rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) method coupled with stable isotope deuterium-labeling is developed and validated to simultaneously quantify naringin as well as its major human gut microbial metabolites naringenin and 3-(4′-hydroxyphenyl) propanoic acid. By eliminating the matrix interferences, this strategy not only confirms naringenin and 3-(4′-hydroxyphenyl) propanoic acid as the predominant metabolites which contribute to the pharmacological effects of naringin but also provides a suitable choice for other flavonoid pharmacokinetics study.

Density-dependent resistance protectsLegionella pneumophilafrom its own antimicrobial metabolite, HGA

To persist in the extracellular state, the bacterial pathogenLegionella pneumophilamust withstand competition from neighboring bacteria. Here, we find thatL. pneumophilacan antagonize the growth of neighboringLegionellaspecies using a secreted inhibitor: HGA (homogentisic acid), the unstable, redox-active precursor molecule toL. pneumophila’s brown-black pigment. Unexpectedly, we find thatL. pneumophilacan itself be inhibited by HGA secreted from neighboring, isogenic strains. Our genetic approaches further identifylpg1681as a gene that modulatesL. pneumophilasusceptibility to HGA. We find thatL. pneumophilasensitivity to HGA is density-dependent and cell intrinsic. This resistance is not mediated by the stringent response nor the previously describedLegionellaquorum-sensing pathway. Instead, we find thatL. pneumophilacells secrete HGA only when they are conditionally HGA-resistant, which allows these bacteria to produce a potentially self-toxic molecule while restricting the opportunity for self-harm. We speculate that establishedLegionellacommunities may deploy molecules such as HGA as an unusual public good that can protect against invasion by low-density competitors.