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A library of C-3 functionalized flavones was successfully provided via palladium-catalyzed amino- and aryloxycarbonylation reactions of 3-iodoflavone (1), under mild conditions. This methodology showed good functional group tolerance using a variety of amines and phenols, under an atmospheric pressure of carbon monoxide as a carbonyl source. While the flavone-3-carboxamides (2a-t) were produced in 22–79%, the flavone-3-carboxylates (4a′-l′) were obtained in excellent yields (up to 88%), under identical reaction conditions, just by switching N-nucleophiles to O-nucleophiles. The convenient availability of the involved starting materials confers simplicity to this approach to design new C-3-substituted flavones of biological relevance. The solid-state structures of flavone-3-carboxamide (2r) and flavone-3-ester (4f′) were further studied by single-crystal XRD analysis. [ABSTRACT FROM AUTHOR]

The toxic nature of bacterial endotoxins is affected by the structural details of lipid A, including the variety and position of acyl chains and phosphate group(s) on its diglucosamine backbone. Negative-ion mode tandem mass spectrometry is a primary method for the structure elucidation of lipid A, used independently or in combination with separation techniques. However, it is challenging to accurately characterize constitutional isomers of lipid A extracts by direct mass spectrometry, as the elemental composition and molecular mass of these molecules are identical. Thus, their simultaneous fragmentation leads to a composite, so-called chimera mass spectrum. The present study focuses on the phosphopositional isomers of the classical monophosphorylated, hexaacylated Escherichia coli-type lipid A. Collision-induced dissociation (CID) was performed in an HPLC-ESI-QTOF system. Energy-resolved mass spectrometry (ERMS) was applied to uncover the distinct fragmentation profiles of the phosphorylation isomers. A fragmentation strategy applying multi-levels of collision energy has been proposed and applied to reveal sample complexity, whether it contains only a 4′-phosphorylated species or a mixture of 1- and 4′-phosphorylated variants. This comparative fragmentation study of isomeric lipid A species demonstrates the high potential of ERMS-derived information for the successful discrimination of co-ionized phosphorylation isomers of hexaacylated lipid A. [ABSTRACT FROM AUTHOR]

Lipid A, the inflammatory portion of lipopolysaccharides (LPS, endotoxins), is the main component of the outer membrane of Gram-negative bacteria. Its bioactivity in humans and animals is strictly related to its chemical structure. In the present work, the fragmentation patterns of the singly charged monosodium [M + Na]+ and disodium [M – H + 2Na]+ adducts, as well as the protonated form of monophosphorylated lipid A species were investigated in detail using positive-ion electrospray ionization-based tandem (MS/MS) and multistage mass spectrometry (MSn) with low-energy collision-induced dissociation (CID). Several synthetic and native lipid A samples were included in the study. We found that the fragmentation pattern of disodiated lipid A is quite similar to that of the well-characterized deprotonated lipid A molecule (typically detected in the negative-ion mode), while the fragmentation pattern of monosodiated lipid A contains fragment ions similar to those of both protonated and deprotonated lipid A molecules. In summary, we propose a new mass spectrometry approach based on the fragmentation regularities of only positively charged precursor ions to dissect the location of the phosphate group and fatty acid moieties on monophosphorylated lipid A. Moreover, this study provides a better understanding of the so-called "chimera mass spectra", which are commonly detected during the fragmentation of native lipid A samples containing both C-1 and C-4′ phosphate positional isomers but rarely identified in negative-ion mode. [ABSTRACT FROM AUTHOR]