Biosynthesis of azaphilones: a review.

Covering up to 2020 Azaphilones are fungal polyketide pigments bearing a highly oxygenated pyranoquinone bicyclic core; they are receiving a great deal of increasing research interest for their applications in the agroalimentary, dyeing, cosmetic, printing and pharmaceutical industries. Their biosynthetic pathways are not fully elucidated; however, thanks to recent genomic approaches combined with the increasing genome sequencing of fungi, some of these pathways have been recently unveiled. This is the first review on the biosynthesis of azaphilonoids adressed from a genomic point of view.

New antibacterial cadiolide analogues active against antibiotic-resistant strains.

The synthesis of new cadiolide analogues was carried out using a one-pot multi component synthesis. The antibacterial activity of these molecules was evaluated on standard and antibiotic resistant bacterial strains chosen for their involvement in human health or in food-born poisoning. Four molecules have shown good activities with MICs of 2 µg/mL-1. The introduction of an indole group or the conversion of the lactone into lactam have highlighted two new families of molecules with promising antibacterial activity. In addition, most of these active molecules are devoid of cytotoxic activity against keratinocyte cells.

Two-Photon Absorption and Cell Imaging of Fluorene-Functionalized Epicocconone Analogues.

Epicocconone 1 is a natural chromophore isolated from the fungus Epicoccum nigrum that has shown applications in proteomics and fluorescent microscopy thanks to its unique pro-fluorescence properties. The modification of the skeleton of the natural product by replacing the triene side chain by a fluorenyl scaffold can noticeably increase the fluorophore's absorption coefficient. The synthesis of the analogues of the natural product has been made possible by the use of a palladium-catalyzed carbonylation reaction, allowing the construction of the ß-keto-dioxinone key intermediate. Two-photon absorption cross-section measurements of the fluorenyl epicocconone analogues show a structure dependency with values ranging from 60 to 280 GM and live cell imaging show intense staining of intracellular vesicle-like structures around the nucleus.

Synthesis and antibacterial activities of cadiolides A, B and C and analogues.

The one-pot multicomponent synthesis of natural butenolides named cadiolides A, B, C and analogues has been realized. The antibacterial structure activity relationship shows that the presence of phenolic hydroxyl groups and the number and position of bromine atoms on the different aromatic rings are important features for antibacterial activity, besides it was demonstrated the tolerance of both benzene and furan ring at position 3 of the butenolide nucleus. Furthermore, none of the most relevant antibacterial compounds showed any cytotoxicity in freshly isolated human neutrophils.

Evaluating charge transfer in epicocconone analogues: toward a targeted design of fluorophores.

Through-space charge transfers upon photon absorption in aminated epicocconone analogues, which serve as promising proteins markers, are investigated within time-dependent density functional theory using total densities differences and various point-charge models (with a special emphasis on Bader's atoms-in-molecules theory). In particular, the distances and the amounts of charge transfer, as well as the transition dipole moments, are discussed from a methodological point of view, and their values are subsequently linked with the chemical structures of these efficient fluorophores. Finally, on the basis of these theoretical findings, several hints for the future improvement of the photochemical properties of these analogues are advanced.

Synthesis of pyrido[2,1-a]isoquinolin-4-ones and oxazino[2,3-a]isoquinolin-4-ones: new inhibitors of mitochondrial respiratory chain.

Benzo[a]quinolizine is an important heterocyclic framework that can be found in numerous bioactive compounds. The general scheme for the synthesis of these compounds was based on the preparation of the appropriate dihydroisoquinolines by Bischler-Napieralski cyclization with good yields, followed by the Pemberton method to form the oxazinones or pyridones derivatives via acyl-ketene imine cyclocondensation. All the synthesized compounds were assayed in vitro for their ability to inhibit mitochondrial respiratory chain. Most of the tested compounds were able to inhibit the integrated electron transfer chain, measured as NADH oxidation, which includes complexes I, III and IV, in the low micromolar range. Oxazino[2,3-a]isoquinolin-4-ones displayed greater activity than their pyrido[2,1-a]isoquinolin-4-ones analogs. Indeed, the presence of a furan ring in C2 position of oxazino[2,3-a]isoquinolin-4-ones provided the compound (1g) with the most potent biological activity. Therefore, these compounds and especially the oxazinone derivatives are in the tendency of the new less toxic antitumor agents that target mitochondrial electron transport chain in a middle range potency.

Electronic excitations in epicocconone analogues: TDDFT methodological assessment guided by experiment.

In this work we present a combined theoretical and experimental study of UV/vis absorption spectra of novel organic chromophores derived from epicocconone. A computational protocol, consistent with experimental findings, is proposed in the framework of time-dependent density functional theory. More precisely, the influence of density functional, basis set, and solvation effects is assessed through theory-experiment matching. On the one hand, it is shown that global hybrid functionals fail to describe excitation spectra for the whole training set. On the other hand, range-separated hybrids allow a description of the complete set of epicocconone derivatives on equal footing, while the double-ζ basis set is shown to be sufficiently accurate for the screening of the spectroscopic properties in epicocconone analogues. The inclusion of solvent effects within a polarizable continuum model appears to be compulsory to decrease the residual dispersion. State specific solvation, on the contrary, does not provide a significant consistency/accuracy improvement. Besides, conformational transformations in investigated compounds and their influence on electronic absorption spectra are pointed out. A systematic choice of the same conformation for each compound from the training set enhances consistency and accuracy of our theoretical model. Lastly, a TDDFT-based calibration is proposed for prediction of absorption wavelengths in epicocconone analogues.

PegPhos: a monodentate phosphoramidite ligand for enantioselective rhodium-catalysed hydrogenation in water.

A BICOL derived monodentate phosphoramidite ligand gives ee's up to 89% in the enantioselective Rh-catalysed hydrogenation of N-acyl dehydroalanine using water as the solvent.

Amine capture strategy for peptide bond formation by means of quinolinium thioester salts.

A new and unprecedented exploitation of quinolinium thioester salts 2 in peptide bond formation is reported. These synthetic tools were assessed during the preparation of a number of dipeptides 3a-f obtained in good yields with complete stereochemical integrity. A sequential mechanism related to a prior amine capture strategy is well-established. Additionally, a tripeptide 3g was prepared according to a "safety-catch" approach, thus demonstrating the important potential of these new synthetic tools in the design of new safety-catch linkers exploitable in Solid-Phase Peptide Synthesis (SPPS).