Synthesis of Selenium Derivatives using Organic Selenocyanates as Masked Selenols: Chemical Reduction with Rongalite as a Simpler Tool to give Nucleophilic Selenides.

The chemical reduction within a family of organic selenocyanates, as masked selenols, using reducing agents, such as Rongalite, sodium dithionite, and sodium thiosulfate is investigated. Using Rongalite, the corresponding diselenides were obtained quantitatively and selectively in very good to excellent yields (51-100 %) starting from alkyl, aryl, and benzyl selenocyanates. The scope of the reaction is unaffected by the electronic nature of the substituents. Furthermore, the reducing agent, Rongalite, is compatible with hydrolysable and reducing-sensitive functional groups. Additionally, a simple methodology employing the in-situ generated benzyl selenolate anion (PhCH2Se-) to promote aliphatic nucleophilic substitution, epoxide ring opening, and Michael addition reactions has been developed; thus, extending the structural diversity of the synthesized selenium derivatives.

Metal- and base-free, aerobic photoredox catalysis with riboflavin to synthesize 2-substituted benzothiazoles.

Sustainable approaches for the synthesis of 2-substituted benzothiazoles are sought after for their use in organic chemistry, bioorganic chemistry, and industrial applications. Here, we described a visible light-driven photoredox catalytic cyclization of thioanilides to afford 2-substituted benzothiazoles using riboflavin as a photocatalyst, where oxygen is used as a clean oxidant and ethanol as a greener solvent. These results provide a new photochemical route for environmentally benign synthesis.

An integrative view on glucagon function and putative role in the progression of pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC).

Cancer metabolism research area evolved greatly, however, is still unknown the impact of systemic metabolism control and diet on cancer. It makes sense that systemic regulators of metabolism can act directly on cancer cells and activate signalling, prompting metabolic remodelling needed to sustain cancer cell survival, tumour growth and disease progression. In the present review, we describe the main glucagon functions in the control of glycaemia and of metabolic pathways overall. Furthermore, an integrative view on how glucagon and related signalling pathways can contribute for pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC) progression, since pancreas and liver are the major organs exposed to higher levels of glucagon, pancreas as a producer and liver as a scavenger. The main objective is to bring to discussion some glucagon-dependent mechanisms by presenting an integrative view on microenvironmental and systemic aspects in pNETs and HCC biology.

Mechanistic Insight into the Light-Triggered CuAAC Reaction: Does Any of the Photocatalyst Go?

The attainment of transition-metal catalysis and photoredox catalysis has represented a great challenge over the last years. Herein, we have been able to merge both catalytic processes into what we have called "the light-triggered CuAAC reaction". Particularly, the CuAAC reaction reveals opposite outcomes depending on the nature of the photocatalyst (eosin Y disodium salt and riboflavin tetraacetate) and additives (DABCO, Et3N, and NaN3) employed. To get a better insight into the operating processes, steady-state, time-resolved emission, and laser flash photolysis experiments have been performed to determine reactivity and kinetic data. These results, in agreement with thermodynamic estimations based on reported data, support the proposed mechanisms. While for eosin Y (EY), Cu(II) was reduced by its triplet excited state; for riboflavin tetraacetate (RFTA), mainly triplet excited RFTA state photoreductions by electron donors as additives are mandatory, affording RFTA•- (from DABCO and NaN3) or RFTAH• (from Et3N). Subsequently, these species are responsible for the reduction of Cu(II). For both photocatalysts, photogenerated Cu(I) finally renders 1,2,3-triazole as the final product. The determined kinetic rate constants allowed postulating plausible mechanisms in both cases, bringing to light the importance of kinetic studies to achieve a strong understanding of photoredox processes.

Riboflavin as Photoredox Catalyst in the Cyclization of Thiobenzanilides: Synthesis of 2-Substituted Benzothiazoles.

Benzothiazoles are synthesized from thiobenzanilides using riboflavin as a photosensitizer and potassium peroxydisulfate as a sacrificial oxidizing agent under visible light irradiation. The methodology accepts a broad range of functional groups and affords the 2-substituted benzothiazoles by transition-metal-free organic photoredox catalysis under very mild conditions.

Thiol-free chemoenzymatic synthesis of ß-ketosulfides.

A preparation of ß-ketosulfides avoiding the use of thiols is described. The combination of a multicomponent reaction and a lipase-catalysed hydrolysis has been developed in order to obtain high chemical diversity employing a single sulfur donor. This methodology for the selective synthesis of a set of ß-ketosulfides is performed under mild conditions and can be set up in one-pot two-step and on a gram-scale.

Regioselective Photocycloaddition of Saccharin Anion to π-Systems: Continuous-Flow Synthesis of Benzosultams.

Saccharin is a versatile scaffold to build up different heterocycles with relevance in asymmetric catalysis, agricultural chemistry, medicinal chemistry, and so forth. Here, we report a photochemical strategy to obtain seven-membered ring benzosultams in one step, using saccharin anion as starting material. The reaction can be improved in a photoflow reactor and its scope was evaluated. Furthermore, computational study at the CASPT2//CASSCF level of theory was also performed to rationalize the involved mechanism.

Metal- and photocatalyst-free synthesis of 3-selenylindoles and asymmetric diarylselenides promoted by visible light.

A novel and sustainable procedure was developed for the synthesis of 3-selenylindoles employing diorganyl diselenides and indoles or electron-rich arenes as starting materials. Visible blue light was used to promote the reaction without employing transition metal complexes or organic photocatalysts as sensitizers. Additives such as strong oxidants or bases were not required. Moreover, ethanol was employed as a benign solvent under mild reaction conditions. Through this easy and eco-friendly approach, several 3-selenylindoles and a number of asymmetric diarylselenides were obtained in good to excellent isolated yields.

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions.

Alkynyl selenides were synthesized by a straightforward one-pot and three-step methodology, without the need of diselenides as starting reagents, under an oxygen atmosphere and using PEG 200 as the solvent. This procedure involves the in situ generation of dialkyl diselenides through a K3PO4-assisted reaction of an alkyl selenocyanate obtained by a nucleophilic substitution reaction between KSeCN and alkyl halides. Successive reaction with terminal alkynes in the presence of t-BuOK affords the corresponding alkyl alkynyl selenide in moderate to good yields. Finally, this methodology allowed the synthesis of 2-alkylselanyl-substituted benzofuran and indole derivatives starting from convenient 2-substituted acetylenes.

Photochemistry of N-(selenoalkyl)-phthalimides. Formation of N, Se-heterocyclic systems.

A variety of N-(selenomethyl)alkyl-phthalimides (alkyl = -(CH2)n-; n = 2-5, 1a, b, d, e) and N-(selenobenzyl)propyl phthalimide (1c) were synthesized and their photochemistry was studied at λ = 300 nm. Steady-state photolysis and laser time-resolved spectroscopy studies confirmed that these reactions proceeded by direct or acetone-sensitized excitation followed by intramolecular electron transfer (ET) between Se atom and the phthalimide moiety. Two main pathways are possible after ET: proton transfer to the ketyl radical anion from the CH3Se(+)˙ or the -CH2Se(+)˙- moieties, yielding the corresponding biradicals. Collapse of these biradicals yields cyclization products with the respective endo or exo selenium-containing heterocycles. Competition between both proton transfer processes depends on the chain length of the alkyl spacer between the phthalimide and Se groups as well as the size of the cycle being formed.

Stereoselective one-pot synthesis of ß-alkylsulfide enol esters. Base-triggered rearrangement under mild conditions.

A stereoselective one-pot procedure was developed to prepare S-substituted (Z)-enol esters through a base-triggered rearrangement. This transition metal-free multicomponent approach can be performed under an air atmosphere at room temperature, tolerates a wide set of chemical functionalities and generally affords high isolated yields. The (Z)-selectivity arises from the [1,4]-S- to O-acyl migration.