NEW METHODOLOGIES FOR PRODUCTS OF BIOLOGICAL INTEREST BY SUITABLY SUBSTITUTED FURANS

Furans represent an interesting class of heterocycles. New synthetic methods for their preparation and elaboration have been described that provide a significant tool for glycosides and lignan-like compounds with important implications in pharmacological applications. In particular, a novel methodology based on a one-pot process starting from glycosyl furans has been developed for the synthesis of spiro compounds and, in particular, of new chiral [6,6]-, [5,6]- and [5,5]-spiroketals of sugars. The spiroketal moiety represents a privileged substructure since it can be found in many simple as well as complex natural products characterized by important and assorted biological properties, from antibiotic to anticancer. It is to be noted that despite numerous methodologies for spiro compounds few synthetic strategies for derivatives oxidized at the 2-position are reported. Novel pyridazine C-nucleosides have also been synthetized by a one-pot procedure. The pyridazine nucleus and its 3-oxo derivatives have been recognized as versatile pharmacophores and great attention in last years has been devoted to the synthesis of these compounds. Interesting results have been obtained in the field of polysustituted furans. Indeed, starting from aryl trisubstituted derivatives a novel synthetic method for diarylfurans with a lignan backbone has been developed using a variant of the Friedel-Crafts reaction. Preliminary biological tests have evidenced antibiotic activities of some derivatives. The presence of furan system in these compounds highlights manifold elaborations of the heterocyclic ring to a variety of product types. In this context, in the field of dye-sensitized photooxygenation, starting from some trisubstituted furans bearing b,b’electron withdrawing groups, previously not investigated, useful C-4 synthons have been obtained in excellent yields in one-pot manner. All the reaction conditions, based on the combination of photooxygenation with reduction or basic treatment, are particularly mild respect to classical oxidation procedures, often not compatible with functional groups which are frequently present in synthetic intermediates. Hence these procedure represents useful alternatives to classical methods. Many of compounds prepared have various lignan-like structures that confirm the role of furans in the synthesis of interesting products

Photochemical Behaviour of Carbamates Structurally Related to Herbicides in Aqueous Media: Nucleophilic Solvent Trapping versus Radical Reactions

Irradiation ofN-arylO-aryl carbamates has been carried out in H2O/CH3CN (1 : 1 v/v) solutions atλ>290 nm. When chlorine is on theN-aryl ring, halogen-substituted products are found. These photoproducts derive from the trapping of the intermediate radical cation by water and, even, by acetonitrile leading to phenols andN-arylacetamides (photo-Ritter products), respectively. UnsubstitutedN-aryl carbamates slowly undergo photo-Fries reaction

Spiroketals of monosaccharides by dye-sensitized photooxygenation of furyl ketoses

[4+2] Cycloaddition of singlet oxygen to suitably substituted furans followed by reduction of the corresponding endoperoxides afforded functionalized enediones which quickly cyclized into the titled spiroketals. The reported method represents a green synthetic one-pot procedure for novel [6,6]-, [5,6]-, and [5,5]-spiroketals of sugars

Nuovi Spirochetali di Monosaccaridi via Furil Chetosi

In questa comunicazione sono riportati i risultati conseguiti nell'ambito di un progetto indirizzato alla sintesi di nuovi glicosidi funzionalizzati e C-nucleosidi mediante reazioni di [4+2] cicloaddizione di ossigeno singoletto su furani sostituiti con residui di monosaccaridi. In particolare, attraverso l'uso della procedura di fotoossigenazione sensibilizzata da coloranti applicata ad opportuni furil chetosi sono stati preparati nuovi [6,6]-, [6,5]- e [5,5]-spirochetali il cui motivo rappresenta un requisito strutturale comune a numerosi derivati semplici o complessi di origine naturale dalle differenziate proprietà biologiche

Photooxygenation of Electron-Poor Trisubstituted Furans: Novel Aspects and Applications

Photooxygenation of titled furans followed by redn. gives unsatd. 4-​oxoaldehydes quant. Some derivs. cyclize under slightly acid conditions or by silica gel to unusual 5,​6- dioxabicyclo[2.1.1]​hexenes and​/or 5H-​furanones. Under appropriate basic conditions 4-​oxocarboxylic acids or their ring-​tautomers 5-​hydroxyfuranones are chemoselectively obtained in almost quant. yields. All the procedures are one-​pot and occur stereoselectively. Due to the electron-​poor substituents alternative non-​photochem. oxidative methods fail or give not cleanly reaction mixts

Furanyl Alcohols as Alkylating Reagents in Friedel-Crafts Reaction of Arenes

Furanyl alcohols react with arenes by a variant of the Friedel–Crafts reaction to give benzyl furans with fairly satisfying yields. The reaction is mediated by Tf2O and occurs with reduced times in the presence of Ph3PO. Some prepared compounds exhibit a lignan-like backbon

Rearrangements vs fragmentations in the dye-sensitized photooxygenation of N-aryl α-Furanamides

The reaction of variously N-substituted α -furanamides with singlet oxygen has been examined. In addition to the expected fragmentation products the reaction affords rearranged 5-hydroxy- and 5-aryloxy-2(5H)-furanones. Products distribution depends on diverse factors: the presence of α -hydrogen, the presence of the amidic group, the nature and the number of nitrogen substituents. The rearrangement to 5-aryloxy-2(5H)- furanones is unreported

Antimicrobial and anti-biofilm properties of novel synthetic lignan-like compounds

Antibiotic resistance and biofilm tolerance are among the principal factors involved in the persistence of chronic infections. The need for new antimicrobials is an ever-increasing challenge in clinical environments and in the control of global health. Arylfurans form a set of structures that have been identified in many natural products, e.g. lignans. Lignans are a sub-group of non-flavonoid polyphenols that play an active role in plants’ defense against bacteria and fungi infections. The aim of this study was to identify novel synthetic arylfurans and lignan-like arylbenzylfurans exhibiting antimicrobial properties. The molecules synthetized were tested against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and S. epidermidis. We found that among tested compounds, arylbenzylfuran 11 was active against S. aureus and S. epidermidis with an MIC of 4 μg ml-1. Compound 11 was also active on methicillin-resistant S. aureus and S. epidermidis. By confocal laser scanning microscopy, we showed that 32 μg ml-1 of compound 11 was able to induce a significant reduction in S. aureus and S. epidermidis biofilms viability. Finally, we demonstrated that compound 11 was not cytotoxic on HaCat cells up to 128 μg ml-1. This work shows the antimicrobial and anti-biofilm potential of a synthetic lignan-like furan

Antimicrobial and anti-biofilm properties of novel synthetic lignan-like compounds

Antibiotic resistance and biofilm tolerance are among the principal factors involved in the persistence of chronic infections. The need for new antimicrobials is an ever-increasing challenge in clinical environments and in the control of global health. Arylfurans form a set of structures that have been identified in many natural products, e.g. lignans. Lignans are a sub-group of non-flavonoid polyphenols that play an active role in plants' defense against bacteria and fungi infections. The aim of this study was to identify novel synthetic arylfurans and lignan-like arylbenzylfurans exhibiting antimicrobial properties. The molecules synthetized were tested against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and S. epidermidis. We found that among tested compounds, arylbenzylfuran 11 was active against S. aureus and S. epidermidis with an MIC of 4 μg ml-1. Compound 11 was also active on methicillin-resistant S. aureus and S. epidermidis. By confocal laser scanning microscopy, we showed that 32 μg ml-1 of compound 11 was able to induce a significant reduction in S. aureus and S. epidermidis biofilms viability. Finally, we demonstrated that compound 11 was not cytotoxic on HaCat cells up to 128 μg ml-1. This work shows the antimicrobial and anti-biofilm potential of a synthetic lignan-like furan