All marine saponins isolated from Pandaros acanthifolium feature a unique and distinctive enone system located in the D ring and an unusual cis-C/D ring junction, presenting an intriguing yet unattained synthetic challenge. The first total synthesis of pandaroside D (1) and its methyl ester (2) was achieved from commercially available dehydroisoandrosterone acetate (DHEA). A notable feature of this synthesis is direct oxidation of the C-15 position promoted by the Davis reagent. This concept was applied despite the negative results of such an attempt described in the literature and confirmed the possibility of using the reagent in the direct construction of the enone system in ring D. For the final step, the reaction with sugar trichloroacetimidate proved unpromising; however, glycosylation of synthesized aglycone was successfully achieved using the classical Koenigs-Knorr variant with methyl 2,3,4-tri-O-acetyl-β-d-glucuronate bromide.

We demonstrate the application of chiral magnesium complexes in an asymmetric carbon-sulfur bond-forming reaction. Enantioselective and cost-effective methodology under mild condition for the thia-Michael addition, utilizing an in situ generated chiral dinuclear magnesium-ProPhenol complex, has been developed. The versatility of this protocol is demonstrated with a broad range of thiol nucleophiles and a wide selection of enones. Enantioenriched beta-ketosulfides are obtained in good to excellent yields and moderate to excellent enantioselectivity. The presented catalytic system exhibits excellent tolerance for structurally different substrates while maintaining high enantioselectivity. This observation aligns with proposed mechanism, wherein the sulfur atom coordinates to the catalyst in close proximity to the reaction center.

Nicotinamide N-methyltransferase (NNMT, EC 2.1.1.1.) plays an important role in the growth of many different tumours and is also involved in various non-neoplastic disorders. However, the presence and role of NNMT in the endothelium has yet to be specifically explored. Here, we characterized the functional activity of NNMT in the endothelium and tested whether NNMT regulates endothelial cell viability. NNMT in endothelial cells (HAEC, HMEC-1 and EA.hy926) was inhibited using two approaches: pharmacological inhibition of the enzyme by NNMT inhibitors (5-amino-1-methylquinoline - 5MQ and 6-methoxynicotinamide - JBSF-88) or by shRNA-mediated silencing. Functional inhibition of NNMT was confirmed by LC/MS/MS-based analysis of impaired MNA production. The effects of NNMT inhibition on cellular viability were analyzed in both the absence and presence of menadione. Our results revealed that all studied endothelial lines express relatively high levels of functionally active NNMT compared with cancer cells (MDA-MB-231). Although the aldehyde oxidase 1 enzyme was also expressed in the endothelium, the further metabolites of N1-methylnicotinamide (N1-methyl-2-pyridone-5-carboxamide and N1-methyl-4-pyridone-3-carboxamide) generated by this enzyme were not detected, suggesting that endothelial NNMT-derived MNA was not subsequently metabolized in the endothelium by aldehyde oxidase 1. Menadione induced a concentration-dependent decrease in endothelial viability as evidenced by a decrease in cell number that was associated with the upregulation of NNMT and SIRT1 expression in the nucleus in viable cells. The suppression of the NNMT activity either by NNMT inhibitors or shRNA-based silencing significantly decreased the endothelial cell viability in response to menadione. Furthermore, NNMT inhibition resulted in nuclear SIRT1 expression downregulation and upregulation of the phosphorylated form of SIRT1 on Ser47. In conclusion, our results suggest that the endothelial nuclear NNMT/SIRT1 pathway exerts a cytoprotective role that safeguards endothelial cell viability under oxidant stress insult.

A visible-light-mediated process for dehydrogenation of amines has been described. The given protocol showed a broad substrate scope, mild reaction conditions and excellent results without the requirement of tedious purification. This process can be applied in one-pot functionalization of secondary amines with various nucleophiles through the cooperation of visible-light and Lewis acid catalysis, leading to the structurally varied essential components of biologically active molecules. In addition, Stern-Volmer studies and quenching experiments revealed the role of a catalyst and led to the proposed mechanism of this transformation.

Synthesis of five Electron Withdrawing Group (EWG) activated Hoveyda-Grubbs’ catalysts containing thioperfluoroalkyl, sulfone and ketone functions is reported. The catalytic activity of these catalysts was well correlated with the σp values of the Hammett constants for the respective EWGs. Importantly, one of new catalysts gave good results in synthesis of a macrocyclic precursor of anti-HCV agent BILN2061.

Tributyl- or triphenylphosphine promotes a one-pot, three-step method for the synthesis of differently substituted dibenzodiazepinones fromN-aryl-2-nitroanilines. Pyridine analogues and the corresponding thiazepinones can also be formed using this method. The process involves deoxygenation of the nitro group, then formation of an iminophosphorane intermediate and its intramolecular condensation with a carboxyl group placed in theN-aryl group. The role of the carboxyl group in the formation of the iminophosphorane and the mode of cyclization are discussed.

Nitrobenzyl benzothiazol-2-yl sulfones and nitrobenzyl 1-phenyl-1H-tetrazol-5-yl sulfones react with chlorides of aromatic acids to form β-acyl derivatives. These products undergo the Smiles rearrangement resulting in the formation of the corresponding nitrophenyl arylacetylenes in 50–60% overall yields (approx. 75% per step). Sulfones bearing CF3 or CN groups instead of a NO2 substituent form mixtures of the acetylenes in moderate yields and benzyl aryl ketones in yields above 40%.

A class of dialkylamino-substituted dibenzodiazepines and their hetero analogues was synthesized by the intramolecular aza-Wittig condensation of the amido group with iminophosphoranes. The one-pot, two-step procedure includes reductive synthesis of the intermediate iminophosphoranes from the corresponding nitroamides and tributylphosphine.

A synthesis of triazole-substituted 1-arylquinoxaline derivatives from halogenated 2-nitrosodiarylamines by two routes is presented.Regioselective substitution of fluorine or chlorine in the starting compounds by sodium azide followed by double cyclocondensation of both the azide substituent and the nitrosoamine group leads to functionalized 2-methylenequinoxaline derivatives.The alternative route separates the two cyclocondensation reactions, allowing obtention of triazole-substituted quinoxalin-2-one derivatives by using two different dicarbonyl reagents.

Starting from 2,4-dinitrotoluene and aldehydes, 2-substituted 6-nitroindoles with alkyl, cycloalkyl, aryl and heteroaryl (thienyl, furyl, pyridyl) substituents in the 2-position of the indole ring were synthesized. This methodology can be used for synthesis of indoles with non-racemic substituents.

A carbanion of tert-butyl 3-(1-pyrrolidinyl)crotonate adds to nitrobenzenes to form σH-adducts, which in the presence of pivaloyl chloride and triethylamine are converted into 3-(1-pyrrolidinyl)quinolines or 3-(1-pyrrolidinyl)quinoline 1-oxides depending on the nitrobenzene structure. This is the first methodology in which a quinoline ring is constructed from a substrate bearing a pyrrolidinyl ring. Starting from optically pure enamines, the method allows synthesis of the corresponding chiral products without racemisation.

Acetylenic carbanions add to nitroarenes (dinitrobenzenes, nitropyridines, etc.) to form σH-adducts that are subsequently oxidized by DDQ according to the oxidative nucleophilic substitution of hydrogen (ONSH) pathway to give nitroaryl acetylenes.

4-Cyanoquinoline-N-oxides were obtained in the reactions of 2-nitrobenzylcyanide carbanions with acrylonitrile.

Title compounds (III) are prepared via reaction of 2-nitrobenzylcyanide carbanions with acrylonitrile (II).

Carbanions of phenylacetonitriles, benzyl sulfones, and dialkyl benzylphosphonates add nitroarenes at the ortho-position to the nitro group to form [Formula: see text]-adducts that, upon treatment with trialkylchlorosilane and additional base (t-BuOK or DBU), transform into 3-aryl-2,1-benzisoxazoles in moderate-to-good yields.