Organic Diselenides: Versatile Reagents, Precursors, and Intriguing Biologically Active Compounds

Abstract

In this account, we describe how some organic diselenides were successfully used in the past as reagents for asymmetric stereoselective synthesis and more recently as precursors of catalysts and reagents applied in new green protocols. A biomimetic approach offered the possibility to perform oxidative reactions using hydrogen peroxide as oxidant and water as medium affording the desired products in excellent yields under mild conditions. The umpolung of the selenium atom gave novel nucleophilic reagents having a strongly accelerated reaction rate in on water conditions. Finally, the use of diselenides to exploit specific biological activities is described here as seminal examples of a promising field of research currently under investigation in our group.

Fluoxetine scaffold to design tandem molecular antioxidants and green catalysts

“…39 Since selenides are largely used in organic synthesis to catalyze oxidation in presence of H 2 O 2 , combined experimental and theoretical mechanistic studies on model organoselenides are important also for designing selenium based organocatalysts. [40][41][42][43][44][45] The rationale that guided the design of the seleniumcontaining analogues of uoxetine aims to combine the antioxidant radical scavenging capacity, within the CNS, of the parent compound with the GPx-like activity of organic selenides in a water-soluble drug-like small molecule (tandem antioxidant). Thus, selenouoxetine and its derivatives here reported represent models for the experimental and theoretical investigation of their elementary, but biologically as well as chemically signicant, reaction with H 2 O 2 .…”

Release of reactive selenium species from phthalic selenoanhydride in the presence of hydrogen sulfide and glutathione with implications for cancer research

“…In this context, the accessibility and reactivity of the selenols (mainly deprotonated at biological pH values) and selenol-derived compounds, such as Se-methyl selenocysteine and diselenides, [16][17][18][19] may be behind the reported chemopreventive activity of different Se-containing compounds, which has been reviewed extensively by numerous authors. 11,[20][21][22][23][24][25] Several mechanisms have been proposed to explain the chemopreventive activity, such as the direct scavenging of free radicals, 26,27 the amelioration of the toxic effects of anticancer drugs, 28 the glutathione peroxidase (GPx)-like activity, 29,30 the protection from toxic elements such as arsenic by protecting PC12 cells from arsenic induced oxidative stress 31 or the protection from radiotherapy, 32 and the modulation of the intracellular redox homeostasis 33 and of the protein kinases. 34 In the last twenty years, H 2 S (H 2 S/HS À /S 2À ) has been emerging as a new gaseous signalling molecule besides nitric oxide ( NO) and carbon monoxide (CO).…”

Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

“…Diphenyl diselenide is a stable compound, currently employed in organic synthesis as catalyst. In combined experimental and theoretical studies, Back and Wirth have extensively explored its catalytic properties and those of its derivatives in numerous reactions [20,[25][26][27][28][29][30][31][32][33][34], while Santi and co-workers have mainly focused on the eco-friendly aspects of the use of diphenyl diselenide in green organic and medicinal chemistry [19][20][21][22][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50].…”

“…More recently, Bhowmick and Mugesh prepared and studied a set of more complex ortho-substituted, amino-based diphenyl diselenide derivatives (20)(21)(22)(23)(24) [167], because the introduction of an additional secondary or tertiary amino moiety or an oxygen atom on the amino-diselenide scaffold, allows to mimic faithfully the structure of the catalytic triad in the GPx enzyme (Schemes 12, 13). In their combined experimental and theoretical studies, Bhowmick and Mugesh observed that an additional amino group enhances the catalytic activity.…”

“…Diorganoyldiselenides are largely employed in organic catalysis too, recently also in water [19][20][21][22]. In this case, the catalytic role of the selenide is to reduce the hydroperoxide, triggering an autocatalytic mechanism and generating in situ a powerful oxidant agent which is much more efficient than the initial hydroperoxide in oxidizing organic substrates [23].…”