Regio- and Stereoselective Synthesis of (Z,Z)-Bis(3-amino-3-oxo-1-propenyl) Selenides and Diselenides Based on 2-propynamides: A Novel Family of Diselenides with High Glutathione Peroxidase-like Activity

Abstract

The efficient regio- and stereoselective syntheses of (Z,Z)-bis(3-amino-3-oxo-1-propenyl) selenides and diselenides in high yields based on the nucleophilic addition of sodium selenide to 2-propynamides and sodium diselenide to 3-(trimethylsilyl)-2-propynamides have been developed. The first examples of the addition of a selenium-centered nucleophile to 2-propynamides with a terminal triple bond and diselenide anion to 3-(trimethylsilyl)-2-propynamides have been carried out. Bis(3-amino-3-oxo-1-propenyl) diselenides are a novel family of compounds, none of which has yet been described in the literature. The glutathione peroxidase-like activity of the obtained compounds has been evaluated and products with high activity have been found. It was established that diselenides are superior to selenides with the same substituents in glutathione peroxidase-like activity. The results of the structural studying of products by single-crystal X-ray diffraction analysis and 77Se-NMR data are discussed.

First Examples of Reactions of 3-Trimethylsilyl-2-Propynamides and Organic Diselenides: Synthesis of Novel Derivatives of Propynamides

“…The synthesis of various vinylic selenides is within the scope of our scientific interests, and a number of effective methods for the preparation of functionalized vinyl and divinyl selenides, including unsubstituted divinyl selenide, have been previously developed [39][40][41][42][43][44][45][46].…”

“…The reaction was carried out through the generation of sodium selenolate 7 from divinyl diselenide 6 under the action of sodium borohydride in a THF/water mixtur followed by the addition of 3-trimethylsilyl-2-propynamide 8 to the reaction mixture a room temperature (Scheme 3). We previously obtained diselenide 6 in a high yiel through the nucleophilic addition of sodium diselenide to 3-trimethylsilyl-2 propynamides [39]. The desilylation reaction of the trimethylsilyl group can occur in the starting 3trimethylsilyl-2-propynamides 1a,b, as well as in the intermediate A, formed by the nucleophilic addition of sodium selenolates to the triple bond (Scheme 2).…”

“…The reaction was carried out through the generation of sodium selenolate 7 from divinyl diselenide 6 under the action of sodium borohydride in a THF/water mixture, followed by the addition of 3-trimethylsilyl-2-propynamide 8 to the reaction mixture at room temperature (Scheme 3). We previously obtained diselenide 6 in a high yield through the nucleophilic addition of sodium diselenide to 3-trimethylsilyl-2propynamides [39]. The reaction was carried out through the generation of sodium selenolate 7 from divinyl diselenide 6 under the action of sodium borohydride in a THF/water mixture, followed by the addition of 3-trimethylsilyl-2-propynamide 8 to the reaction mixture at room temperature (Scheme 3).…”

“…The reaction was carried out through the generation of sodium selenolate 7 from divinyl diselenide 6 under the action of sodium borohydride in a THF/water mixture, followed by the addition of 3-trimethylsilyl-2-propynamide 8 to the reaction mixture at room temperature (Scheme 3). We previously obtained diselenide 6 in a high yield through the nucleophilic addition of sodium diselenide to 3-trimethylsilyl-2-propynamides [39].…”

Recent Developments in the Synthesis of Organoselenium Compounds Based on the Reactions of Organic Diselenides with Acetylenes

“…They are used as precursors of both electrophilic and nucleophilic selenium species, which are usually generated from organic diselenides in situ and involved in various useful transformations. Along with multifaceted applications in organic synthesis, organic diselenides exhibit various biological activities, including high glutathione peroxidase mimetic properties (Figure 1) [29,[34][35][36][37][38][39][40][41][42][43][44][45][46]. One of most important classes of organoselenium compounds are organic diselenides.…”