(Z,Z)-Selanediylbis(2-Propenamides): Novel Class of Organoselenium Compounds with High Glutathione Peroxidase-Like Activity
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molecules Article (Z,Z)-Selanediylbis(2-propenamides): Novel Class of Organoselenium Compounds with High Glutathione Peroxidase-Like Activity. Regio- and Stereoselective Reaction of Sodium Selenide with 3-Trimethylsilyl-2-propynamides Mikhail V. Andreev, Vladimir A. Potapov * , Maxim V. Musalov and Svetlana V. Amosova A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Division of The Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russia; [email protected] (M.V.A.); [email protected] (M.V.M.); [email protected] (S.V.A.) * Correspondence: [email protected] Academic Editor: Derek J. McPhee Received: 3 December 2020; Accepted: 14 December 2020; Published: 15 December 2020 Abstract: The efficient regio- and stereoselective synthesis of (Z,Z)-3,30-selanediylbis(2-propenamides) in 76–93% yields was developed based on the reaction of sodium selenide with 3-trimethylsilyl-2- propynamides. (Z,Z)-3,30-Selanediylbis(2-propenamides) are a novel class of organoselenium compounds. To date, not a single representative of 3,30-selanediylbis(2-propenamides) has been described in the literature. Studying glutathione peroxidase-like properties by a model reaction showed that the activity of the obtained products significantly varies depending on the organic moieties in the amide group. Divinyl selenide, which contains two lipophilic cyclohexyl substituents in the amide group, exhibits very high glutathione peroxidase-like activity and this compound is considerably superior to other products in this respect. Keywords: (Z,Z)-3,30-selanediylbis(2-propenamides); 3-trimethylsilyl-2-propynamides; sodium selenide; glutathione peroxidase-like activity; regioselective reactions; stereoselective reactions; desilylation 1. Introduction Vinyl selenides are important intermediates for organic synthesis [1–9]. These compounds have been used for the preparation of a number of valuable products [4–9]. Vinyl selenides have found application in the synthesis of functionalized ketones, (Z)-allyl alcohols, and unsaturated aldehydes [4]. The cross-coupling of vinyl selenides with terminal alkynes in the presence of a nickel/CuI catalyst at room temperature proceeded with of retention of stereochemical configuration leading to (Z)- and (E)-enyne derivatives in good yields [5]. The coupling reaction of vinyl selenides with Grignard reagents provided corresponding functionalized alkenes [6,7]. The synthesis of resveratrol and its methoxylated analogues—well known compounds due to their anti-inflammatory, anticancer, antibacterial, and neuroprotective activity, has been proposed based on vinyl selenides [8]. An efficient method for preparation of α-phenylselanyl lactones has been developed from α-(phenylseleno)vinyl tozylates [9]. Some vinyl selenides exhibit antioxidant [10], antinociceptive [11], and hepatoprotective activity [12]. Molecules 2020, 25, 5940; doi:10.3390/molecules25245940 www.mdpi.com/journal/molecules Molecules 2020, 25, x FOR PEER REVIEW 2 of 15 Molecules 2020, 25, 5940 2 of 15 The main methods for the preparation of vinyl selenides include a transition metal catalyzed couplingThe mainof vinyl methods halides for with the diselenides preparation or of selenols vinylselenides [13–16], reactions include aof transition thiols or chalcogenolates metal catalyzed couplingwith selenoalkynes of vinyl halides [14,17,18], with diselenides and addition or selenolsof selenium-centered [13–16], reactions nucleophiles of thiols orto chalcogenolatesacetylenes [8,14,19– with selenoalkynes23]. [14,17,18], and addition of selenium-centered nucleophiles to acetylenes [8,14,19–23]. OneOne ofof thethe mostmost usefuluseful andand atom-economicatom-economic method methodss is is based based on on addition addition reactions reactions of of selenoles selenoles oror selenolateselenolate anionsanions withwith acetylenesacetylenes [[8,14,19–22].8,14,19–22]. Examples Examples of of these these reactions reactions refer refer mainly mainly to to vinyl vinyl selenidesselenides containingcontaining aliphaticaliphatic or aromatic substituents at at the the ββ-carbon-carbon atom atom of of the the double double bond. bond. ExamplesExamples ofof thethe synthesissynthesis ofof vinylvinyl selenidesselenides bearin bearingg electron-withdrawing groups groups are are scarce scarce in in the the literature.literature. TheThe synthesis synthesis of of (Z,Z (Z,Z)-bis(2-acylvinyl))-bis(2-acylvinyl) selenides selenides by the by addition the addition reaction reaction of sodium of sodium selenide selenide with organyl ethynyl ketones was developed [23]. with organyl ethynyl ketones was developed [23]. There are only a few representatives of vinyl selenides containing the amide group [24–27]. The There are only a few representatives of vinyl selenides containing the amide group [24–27]. Pd-catalyzed four-component reaction between sulfonamide, alkyne, diphenyl diselenide, and The Pd-catalyzed four-component reaction between sulfonamide, alkyne, diphenyl diselenide, and carbon carbon monoxide afforded substituted 3-(phenylselanyl)propenamides in 65–90% yields [24]. monoxide afforded substituted 3-(phenylselanyl)propenamides in 65–90% yields [24]. Functionalized Functionalized 3-(phenylselanyl)propenamides were obtained in 57–89% yields based on 3- 3-(phenylselanyl)propenamides were obtained in 57–89% yields based on 3-(phenylselanyl)acrylic acid (phenylselanyl)acrylic acid which was synthesized in 65% yield from diphenyl diselenide and ethyl which was synthesized in 65% yield from diphenyl diselenide and ethyl propiolate [25]. The reaction propiolate [25]. The reaction of carbamoselenoate, PhSeC(O)NMe2, with 1-octyne in the presence of of carbamoselenoate, PhSeC(O)NMe2, with 1-octyne in the presence of Pd(PPh3)4 gave 3-hexyl-3- Pd(PPh3)4 gave 3-hexyl-3-(phenylselanyl)propenamide in 40% yield [26]. (phenylselanyl)propenamide in 40% yield [26]. There are no data in the literature about the biological activity of 3-selanylpropenamides. There are no data in the literature about the biological activity of 3-selanylpropenamides. However, However, it is known that vinyl sulfides bearing the amide group in the β-position exhibit anticancer it is known that vinyl sulfides bearing the amide group in the β-position exhibit anticancer [28] and [28] and antifungal [29] activity (Figure 1). Containing the 2-amidovinylsulfonyl group antifungal [29] activity (Figure1). Containing the 2-amidovinylsulfonyl group methylgerambullone methylgerambullone (isolated from Glycosmis angustifolia) acts as the agonist of acetylcholine Glycosmis angustifolia (isolatedreceptors from [30]. Phenoxyquinolines) actsbearing as the a 2-amidov agonist ofinylsulfonyl acetylcholine moiety receptors shows [30]. the Phenoxyquinolines properties of c- bearingMet kinase a 2-amidovinylsulfonyl inhibitors [31] (Figuremoiety 1). Taking shows theinto properties account the of c-Metindicated kinase biological inhibitors properties [31] (Figure of 3-1). Takingsulfanylpropenamides, into account the indicatedit can be assumed biological that properties selenium of analogs 3-sulfanylpropenamides, of these compounds it can can also be assumeddisplay thatsome selenium kinds of analogs biological of theseactivity. compounds Moreover, can the also vinyla displaymide some group, kinds itself, of is biological an important activity. part Moreover, of some thebiologically vinylamide active group, natural itself, iscompounds an important and part phar of somemaceuticals, biologically which active exhibit natural antitumor, compounds anti- and pharmaceuticals,tuberculosis, andwhich anticonvulsant exhibit antitumor, activity [32–36]. anti-tuberculosis, and anticonvulsant activity [32–36]. Me Me O O N S N S Me O Me Me Me O O O Me O Antifungal activity Methylgerambullone (agonist of acetylcholine receptors) Me F Me O O N S N S Me Me Me O Me N Me O NNO 2 O O O MeO HO O Anticancer activity c-Met kinase inhibitor OH N O N N Me FigureFigure 1.1. Known biologically biologically active active derivatives derivatives of of vinyl vinyl sulfides sulfides containing containing the the amide amide group group (anticancer(anticancer [ [28],28], antifungalantifungal [[29],29], agonistagonist of acetylcholine receptors [30], [30], c-Met kinase kinase inhibitor inhibitor [31]). [31]). ToTo date,date, considerableconsiderable eeffortffort hashas beenbeen devoted to the discovery of of compounds compounds that that mimic mimic the the actionaction ofof selenium-containingselenium-containing glutathioneglutathione peroxidase enzymes [37–47]. [37–47]. The The presence presence of of selenium selenium in in thesethese enzymes enzymes largelylargely determinesdetermines the glutathione pe peroxidaseroxidase activity. activity. In In particular, particular, organoselenium organoselenium compoundscompounds bearing bearing amide amide groups groups have have been been shown show to ben to good be catalystsgood catalysts for the reductionfor the reduction of peroxides of andperoxides hydroperoxides and hydroperoxides with thiols with (Figure thiols2). (Figure 2). Molecules 2020, 25, 5940 3 of 15 Molecules 2020, 25, x FOR PEER REVIEW 3 of 15 O O O O O 2 O N R N N N Se N R1 N Se Se Se Se Se Ebselen (antiinflammatory, neuroprotective and GPx-like activity) Ethaselen Propylselen 1,2-Selenazolan-3-ones Me O O Me Se Se 2 O O R HO Se N HO OH N O R1 O HO OH Se R Me N Se C N O O N C H H Me O O 1,2-Benzoselenazin-3-ones Camphor derived selenenamide Benzoselenazolinones Seleninic acid anhydride derivative FigureFigure 2.2. ContainingContaining amide amide