Synthesis of Benzoxazines by Heterogeneous Multicomponent Biochemo Multienzymes Cascade Reaction.

This work describes the possibility to combine multicomponent chemistry and multienzymes cascade transformations in a unique reactive framework to yield highly functionalized 1,4-benzoxazines under favorable heterogeneous conditions. The synthetic scheme involved the generation in situ of electrophilic reactive quinone intermediates of tyrosol esters catalyzed by lipase M and tyrosinase followed by nucleophilic 1,6-Michael addition of selected α-amino acid methyl esters, and successive intramolecular lactonization and aromatization processes. The immobilization of the multienzymes cascade on electroactive lignin nanoparticles improved the sustainability and recyclability of the overall system.

The role of borosilicate glass in Miller-Urey experiment.

We have designed a set of experiments to test the role of borosilicate reactor on the yielding of the Miller-Urey type of experiment. Two experiments were performed in borosilicate flasks, two in a Teflon flask and the third couple in a Teflon flask with pieces of borosilicate submerged in the water. The experiments were performed in CH4, N2, and NH3 atmosphere either buffered at pH 8.7 with NH4Cl or unbuffered solutions at pH ca. 11, at room temperature. The Gas Chromatography-Mass Spectroscopy results show important differences in the yields, the number of products, and molecular weight. In particular, a dipeptide, multi-carbon dicarboxylic acids, PAHs, and a complete panel of biological nucleobases form more efficiently or exclusively in the borosilicate vessel. Our results offer a better explanation of the famous Miller's experiment showing the efficiency of borosilicate in a triphasic system including water and the reduced Miller-Urey atmosphere.

Synthesis and Evaluation of Artemisinin-Based Hybrid and Dimer Derivatives as Antimelanoma Agents.

A library of hybrid and dimer compounds based on the natural scaffold of artemisinin was synthesized. These derivatives were obtained by coupling of artemisinin derivatives, artesunate, and dihydroartemisinin with a panel of phytochemical compounds. The novel artemisinin-based hybrids and dimers were evaluated for their anticancer activity on a cervical cancer cell line (HeLa) and on three complementary metastatic melanoma cancer cell lines (SK-MEL3, SK-MEL24, and RPMI-7951). Two hybrid compounds obtained by coupling of artesunate with eugenol and tyrosol, and one of the dimer compounds containing curcumin, emerged as the most active and cancer-selective derivatives.

L-DOPA-quinone Mediated Recovery from GIRK Channel Firing Inhibition in Dopaminergic Neurons.

The oxidative degeneration of dopamine-releasing (DAergic) neurons in the substantia nigra pars compacta (SNc) has attracted much interest in preclinical research, due to its involvement in Parkinson's disease manifestations. Evidence exists on the participation of quinone derivatives in mitochondrial dysfunction, alpha synuclein protein aggregation, and protein degradation. With the aim to investigate the role of L-DOPA-quinone in DAergic neuron functions, we synthesized L-DOPA-quinone by use of 2-iodoxybenzoic acid and measured its activity in recovery from dopamine-mediated firing inhibition of SNc neurons. Noteworthy, L-DOPA-quinone counteracts firing inhibition in SNc DAergic neurons caused by GIRK opening. A possible mechanism to explain the effect of L-DOPA-quinone on GIRK channel has been proposed by computational models. Overall, the study showed the possibility that L-DOPA-quinone stabilizes GIRK in a preopen conformation through formation of a covalent adduct with cysteine-65 on the GIRK2 subunit of the protein.

Author Correction: Proton irradiation: a key to the challenge of N-glycosidic bond formation in a prebiotic context.

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Regioselective IBX-Mediated Synthesis of Coumarin Derivatives with Antioxidant and Anti-influenza Activities.

Different catechol and pyrogallol derivatives have been synthesized by oxidation of coumarins with 2-iodoxybenzoic acid (IBX) in DMSO at 25 °C. A high regioselectivity was observed in accordance with the stability order of the incipient carbocation or radical benzylic-like intermediate. The oxidation was also effective in water under heterogeneous conditions by using IBX supported on polystyrene. The new derivatives showed improved antioxidant effects in the DPPH test and inhibitory activity against the influenza A/PR8/H1N1 virus. These data represent a new entry for highly oxidized coumarins showing an antiviral activity possibly based on the control of the intracellular redox value.

Proton irradiation: a key to the challenge of N-glycosidic bond formation in a prebiotic context.

The formation of nucleosides in abiotic conditions is a major hurdle in origin-of-life studies. We have determined the pathway of a general reaction leading to the one-pot synthesis of ribo- and 2'-deoxy-ribonucleosides from sugars and purine nucleobases under proton irradiation in the presence of a chondrite meteorite. These conditions simulate the presumptive conditions in space or on an early Earth fluxed by slow protons from the solar wind, potentially mimicking a plausible prebiotic scenario. The reaction (i) requires neither pre-activated precursors nor intermediate purification/concentration steps, (ii) is based on a defined radical mechanism, and (iii) is characterized by stereoselectivity, regioselectivity and (poly)glycosylation. The yield is enhanced by formamide and meteorite relative to the control reaction.