Flávia Manarin

Electrophilic Cyclization of 2-Chalcogenealkynylanisoles: Versatile Access to 2-Chalcogen-benzo[b]furans

An efficient synthesis of 2-chalcogen-3-substituted-benzo[b]furan compounds has been accomplished via electrophilic cyclization reaction of 2-chalcogenealkynyl anisoles using I(2), ICl, Br(2), and PhSeBr as electrophile sources. The product distributions were strongly dependent on the nature of substituents in the aromatic ring of anisole and on the chalcogen atom directly bonded to the triple bond. The 2-chalcogen-3-iodo-benzo[b]furans obtained smoothly underwent conversion to more complex structures of benzo[b]furan derivatives via palladium- or copper-catalyzed cross-coupling reaction with thiols, diphenyl diselenides, and zincates.

FeCl3-Diorganyl Dichalcogenides Promoted Cyclization of 2-Alkynylanisoles to 3-Chalcogen Benzo[b]furans

A general synthesis of 3-chalcogen benzo[b]furans from the readily available 2-alkynylanisoles, via FeCl(3)/diorganyl dichalcogenides intramolecular cyclization, has been developed. Aryl and alkyl groups directly bonded to the chalcogen atom were used as cycling agents. The results revealed that the reaction significantly depends on the electronic effects of substituents in the aromatic ring bonded to the selenium atom of the diselenide species. We observed that the pathway of reaction was not sensitive to the nature of substituents in the aromatic ring of anisole since both the electron-donating and the electron-withdrawing groups delivered the products in similar yields. In addition, the obtained heterocycles were readily transformed to more complex products by using a chalcogen/lithium exchange reaction with n-BuLi followed by trapping of the lithium intermediate with aldehydes, furnishing the desired secondary alcohols in good yields.

Organotellurium and organoselenium compounds attenuate Mn-induced toxicity in Caenorhabditis elegans by preventing oxidative stress.

Organochalcogens have been widely studied given their antioxidant activity, which confers neuroprotection, antiulcer, and antidiabetic properties. Given the complexity of mammalian models, understanding the cellular and molecular effects of organochalcogens has been hampered. The nematode worm Caenorhabditis elegans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging, and in vivo live analysis of toxicity. We previously showed that manganese (Mn)-exposed worms exhibit oxidative-stress-induced neurodegeneration and life-span reduction. Here we use Mn-exposed worms as a model for an oxidatively challenged organism to investigate the underlying mechanisms of organochalcogen antioxidant properties. First, we recapitulate in C. elegans the effects of organochalcogens formerly observed in mice, including their antioxidant activity. This is followed by studies on the ability of these compounds to afford protection against Mn-induced toxicity. Diethyl-2-phenyl-2-tellurophenyl vinyl phosphonate (DPTVP) was the most efficacious compound, fully reversing the Mn-induced reduction in survival and life span. Ebselen was also effective, reversing the Mn-induced reduction in survival and life span, but to a lesser extent compared with DPTVP. DPTVP also lowered Mn-induced increases in oxidant levels, indicating that the increased survival associated with exposure to this compound is secondary to a decrease in oxidative stress. Furthermore, DPTVP induced nuclear translocation of the transcriptional factor DAF-16/FOXO, which regulates stress responsiveness and aging in worms. Our findings establish that the organochalcogens DPTVP and ebselen act as antiaging agents in a model of Mn-induced toxicity and aging by regulating DAF-16/FOXO signaling and attenuating oxidative stress.

Hepatoprotective activity of a vinylic telluride against acute exposure to acetaminophen.

Acetaminophen (APAP) hepatotoxicity has been related with several cases of cirrhosis, hepatitis and suicides attempts. Notably, oxidative stress plays a central role in the hepatic damage caused by APAP and antioxidants have been tested as alternative treatment against APAP toxicity. In the present study, we observed the hepatoprotector activity of the diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP), an organotellurium compound with low toxicity and high antioxidant potential. When the dose of 200 mg/kg of APAP was used, we observed that all used doses of DPTVP were able to restore the -SH levels that were depleted by APAP. Furthermore, the increase in thiobarbituric acid reactive substances levels and in the seric alanine aminotransferase (ALT) activity and the histopathological alterations caused by APAP were restored to control levels by DPTVP (30, 50 and 100 μmol/kg). On the other hand, when the 300 mg/kg dose of APAP was used, DPTVP restored the non-proteic -SH levels and repaired the normal liver morphology of the intoxicated mice only at 50 μmol/kg. Our in vitro results point out to a scavenging activity of DPTVP against several reactive species, action that is attributed to its chemical structure. Taken together, our results demonstrate that the pharmacological action of DPTVP as a hepatoprotector is probably due to its scavenging activity related to its chemical structure.

PhSeBr-catalyzed selective addition of thiols to α,β-unsaturated carbonyl compounds: regioselective synthesis of thioacetals vs. β-mercapto ketones

Apresentamos aqui nossos resultados da adicao de tiois, catalisada por PhSeBr, a compostos carbonilicos α,β-insaturados sob condicoes brandas para obter regiosseletivamente β-mercapto cetonas ou tioacetais com altos rendimentos e seletividade. A reacao foi principalmente controlada pela temperatura, na qual os produtos de adicao 1,4 foram obtidos a temperatura de -20 oC. Inversamente quando a reacao foi realizada sob refluxo, tioacetais foram obtidos como unico produto. O metodo admite diversos grupos funcionais, como alquilicos, benzilicos e arilicos com substituintes neutros, deficientes e ricos em eletrons no anel aromatico.

Palladium catalyzed Suzuki cross-coupling of 3-iodo-2-(methylthio)-benzo[b]furan derivatives: synthesis of 3-aryl-2-(methylthio)benzo[b]furans

A selective and efficient method for the synthesis of 3-aryl-2-(methylthio)benzo[ b]furans derivatives by palladium catalyzed cross-coupling reaction with boronic acids has been developed. The reaction proceeded cleanly under mild conditions and was performed with aryl boronic acids bearing electron-withdrawing, electron donating and neutral substituents.