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Article

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

by
Vladimir A. Potapov
*,
Mikhail V. Andreev
,
Maxim V. Musalov
,
Irina V. Sterkhova
,
Svetlana V. Amosova
and
Lyudmila I. Larina
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Division of The Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russia
*
Author to whom correspondence should be addressed.
Inorganics 2022, 10(6), 74; https://doi.org/10.3390/inorganics10060074
Submission received: 16 May 2022 / Revised: 24 May 2022 / Accepted: 26 May 2022 / Published: 30 May 2022
(This article belongs to the Special Issue Inorganics: 10th Anniversary)
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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.

1. Introduction

Interest in the chemistry of organoselenium compounds has increased significantly in the last few decades due to the discovery of a number of selenoenzymes involved in important physiological processes [1,2,3,4,5]. Selenoenzymes are an important family of mammalian antioxidant biocatalysts that protect cell membranes and other cellular components from oxidative stress. The discovery of the antioxidant enzyme glutathione peroxidase, which contains a selenocysteine fragment in its active site, has made an important contribution to the development of the biochemical role of selenium in the functioning of the mammalian organisms [5,6,7,8,9,10,11,12]. It is worthy to note that the 21st proteinogenic amino acid selenocysteine is the only metalloid-containing biomolecule encoded in human DNA [13].
Organic diselenides represent an important class of organoselenium compounds that are widely used in organic synthesis. Both the electrophilic selenium species and nucleophilic highly reactive selenolates can be generated from organic diselenides and are involved in a variety of further reactions [1,2,3,4,5,14,15,16,17,18] (Figure 1).
Organic diselenides often show glutathione peroxidase-like activity. It is known, for example, that diphenyl diselenide exhibits high glutathione peroxidase-like activity and is used as a standard compound in a series of investigations [19,20,21,22].
It is noteworthy that the presence of amide groups is usually very favorable for exhibiting glutathione peroxidase-like activity [1,2,3,4,5,20,21,22,23,24]. Examples of diselenides and organoselenium compounds, which contain amide groups and exhibit high glutathione peroxidase-like activity, are shown in Figure 2 [20,21,22,23,24]. They include camphor-derived selenenamide [22] and selenazo compounds [25].
Ebselen and its analogue ethaselen contain the selenenamide function in the cycle and exhibit high glutathione peroxidase mimetic properties. Moreover, ebselen shows anti-inflammatory and neuroprotective activity and is also used for the treatment and prevention of cardiovascular diseases and ischemic stroke [20,21,22,23,24,25]. This compound has found therapeutic application and has undergone evaluation in clinical trials as an anti-inflammatory agent.
Divinyl diselenides are a rare class of organoselenium compounds and there are scarce data in the literature on the synthesis and chemical properties of divinyl diselenides [26,27,28,29,30]. Unsubstituted divinyl diselenide was prepared in a 67% yield by the reaction of vinylmagnesium bromide with elemental selenium followed by oxidation of intermediate vinylselanylmagnesium bromide with bromine [26,27]. Vinyl selanylacetates were cleaved by sodium in HMPA or DMF to give vinyl selenolates, which were oxidized by iodine to yield divinyl diselenides with the retention of a configuration of starting vinylic compounds [28]. The insertion of elemental selenium into the Csp2-Zr bond of alkenylchlorozirconocenes, followed by oxidation in air, affords four divinyl diselenides in 67–75% yields [29].
The synthesis of divinyl selenides by electrophilic addition of selenium dihalides to acetylenes [30], including propargylic alcohols [31], was developed. In the case of the reaction of selenium dichloride with propargylic alcohols, it was noted that the preparation of divinyl selenides was accompanied by the formation of the corresponding divinyl diselenides in low yields as by-products. Two substituted bis[(Z)-2-chloro-1-(hydroxymethyl)ethenyl] diselenides were separated from their selenide counterpart by column chromatography. However, the authors of this work were unable to isolate other diselenides by chromatography and their contents were determined by 1H-NMR analysis of the crude reaction mixture [31]. The diselenide formation was explained by the addition reaction of selenium monochloride, Se2Cl2, which was formed via the disproportionation of selenium dichloride [31].
In the last few decades, vinylic selenides have been widely used in organic synthesis as starting materials and versatile intermediates. A number of valuable products have been obtained based on vinylic selenides [32,33,34,35,36,37,38,39]. A representative example is the synthesis of resveratrol and its methoxylated analogues—well-known compounds due to their anti-inflammatory, anticancer, antibacterial and neuroprotective activity [33]. Valuable (Z)- and (E)-enyne derivatives were obtained in good yields by the cross-coupling reactions of vinyl selenides with terminal alkynes with retention of a stereochemical configuration of starting vinylic selenides [34]. The Grignard reagents were involved in the cross-coupling reaction with vinyl selenides, giving corresponding functionalized alkenes [35].
The most useful and atom-economic method for the preparation of vinyl selenides is the addition of selenium-centered nucleophiles to acetylenes [40,41,42,43,44,45]. The syntheses of unsubstituted divinyl selenide, alkyl vinyl selenides and various functionalized divinyl selenides by the addition reaction of selenide anion to the triple bond were developed in this institute with our participation [45,46,47,48,49,50,51].
Furthermore, 2-propynamides are very important reagents for organic synthesis and theoretically can be used for the preparation of vinyl selenides containing amide groups, by nucleophilic addition of selenium-centered nucleophiles to the triple bond. However, 2-propynamides with terminal triple bonds are rarely used in organic synthesis. These compounds are hard to obtain and they are not listed in the catalogs of leading chemical companies. Prior to our research, there were no examples of the addition of selenium-centered nucleophiles to propynamides with terminal triple bonds in the literature.

2. Results and Discussion

The goal of this work is to develop the regio- and stereoselective synthesis of (Z,Z)-bis(3-amino-3-oxo-1-propenyl) selenides and diselenides based on the nucleophilic addition of sodium selenide to 2-propynamides and sodium diselenide to 3-(trimethylsilyl)-2-propynamides.
2-Propynamides 1a–i with the terminal triple bond were obtained in high yields by desilylation of 3-(trimethylsilyl)-2-propynamides under the action of potassium carbonate in methanol at room temperature (Scheme 1).
An efficient and convenient method for the preparation of 3-(trimethylsilyl)-2-propynamides based on propargyl alcohol was previously developed at this institute [52,53,54] and opened up the possibility of using these reagents in organic synthesis [55,56,57,58].
It is noteworthy that one of products 1a–i, N,N-dicyclohexyl-2-propynamide 1g has not been previously described in the literature. The obtained 2-propynamides 1a–i was used in the synthesis of (Z,Z)-bis(3-amino-3-oxo-1-propenyl) selenides 2a–i. Reaction conditions, which allowed the process to take place in a regio- and stereoselective manner, giving the target products in high yields, were developed (Scheme 2).
It was found that favorable conditions for the synthesis of selenides 2a–i include the generation of sodium selenide by the action of sodium borohydride on elemental selenium in water on heating (the temperature of the water bath is 80–85 °C), followed by the addition of a solution of 2-propynamides 1a–i in methanol. The reaction mixture was refluxed for 30 min and the target products were isolated in up to 97% yields after extraction. The synthetic procedure is very convenient and efficient and the reaction conditions include the use of green solvents, such as water and methanol. The synthesis of selenides 2a–i represents the first example of the addition of selenium-centered nucleophiles to 2-propynamides with a terminal triple bond.
The synthesis of (Z,Z)-bis(3-amino-3-oxo-1-propenyl) diselenides has not yet been described in the literature. We devoted our efforts to synthesizing the first representatives of this family of compounds based on elemental selenium and alkynes containing the amide group. We found that diselenides 3a–d can be obtained in a 50–70% yield by the nucleophilic addition of diselenide anion to 3-(trimethylsilyl)-2-propynamides, avoiding the stage of desilylation of the latter compounds (Scheme 3).
The nucleophilic addition of diselenide anion to 3-(trimethylsilyl)-2-propynamides was accompanied by desilylation, which occurred in situ under these conditions. Diselenides 3a–d are a novel family of organoselenium compounds.
Some conclusions can be drawn regarding the 77Se-NMR spectral data of selenides 2a–i and diselenides 3a–d. The introduction of the phenyl substituents to the amide group of selenides led to a downfield shift (compounds 2a, 2c, and 2f), whereas the introduction of the cyclohexyl groups does not have a noticeable effect on the chemical shift (compounds 2a and 2g). Replacing one carbon atom with an electronegative oxygen atom in the piperidine cycle led to a downfield shift (compounds 2i and 2h). Comparing the diselenides 3a–d and selenides 2c,d,f,h bearing the same substituents, we can conclude that the selenium atom in diselenides 3a–d resonates in the downfield region (there is an approximately 40–60 ppm difference in the chemical shifts of diselenides 3a–d and selenides 2c,d,f,h).
The structures of four products, 2a, 2d, 2f, and 2i, were studied by single-crystal X-ray diffraction analysis (Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9 and Figure 10). The amide molecule 2a is characterized by the presence of C2 symmetry, the axis passes through the Se atom. However, the C–Se bond lengths in the molecule are slightly different and there is one molecule in the independent part of the cell. The same is typical for the molecules of amides 2d, 2f, and 2i.
The C–Se–C angles in compounds 2a, 2d, 2f, and 2i represent a ‘V’-shaped configuration around the selenium atom. The values of the C–Se–C angle in compounds 2a, 2d, 2f, and 2i are approximately 92–95°, which are close to the value of this angle in other structures containing the C–Se–C fragment [59,60,61,62,63]. The Se–C bond lengths are 1.892–1.900 Å, which are slightly shorter than in previously described molecules [59,60,61,62,63] (1.930–1.940 Å). Such differences are obviously related to the different temperature conditions of the XRD experiment: amides 2a, 2d, 2f, and 2i were analyzed at the temperature of 100 K, while the known structures [59,60,61,62,63] were determined at room temperature. The Se–C bond length can vary from 1.850–1.920 Å, even in one molecule [62], which is determined by the electronegative properties of substituents at carbon atoms.
Molecules of compounds 2a and 2i crystallize in the orthorhombic system, space group P212121, and amides 2d and 2f crystallize in the monoclinic system, space group P21/n (Figure 3, Figure 4, Figure 5 and Figure 6).
The crystal structure of compound 2a is formed due to intermolecular hydrogen bonds NH···O=C with a length of 2.083–2.140 Å (Figure 7), as well as due to short contacts between the unshared electron pair of the selenium atom and the hydrogen atoms of the CH groups of neighboring molecules (3.043 Å). The molecules of amide 2d in the crystal are interconnected by short CH···O=C contacts approximately 2.3–2.5 Å long (Figure 8).
In contrast to amides 2a, 2d, and 2i, compound 2f, due to bulky phenyl substituents in the crystal, forms significant voids into which solvent molecules, carbon tetrachloride, are embedded. The crystal structure of such a co-crystal is stabilized by the CH···Cl bonds with solvent molecules ~2.9–3.4 Å long (Figure 9). The crystal structure of compound 2i is formed due to short contacts CH···O=C and CH···Se (Figure 10).
The presence of amide groups is favorable for exhibiting glutathione peroxidase-like activity [1,2,3,4,5,20,21,22,23,24], and we evaluated this activity for a novel family of organoselenium compounds, diselenides 3a–d, in comparison with that of selenides 2c, 2d, 2f, and 2h with the same substituents. The known model reaction of oxidation of phenylmethanethiol by tert-butyl hydroperoxide (TBHP) in the presence of the obtained products as catalysts was used, and the progress of this reaction was monitored by 1H NMR spectroscopy [19,20,21,22,23].
It was found that diselenides 3a–d are superior to analogous selenides 2c, 2d, 2f, and 2h with the same substituents in glutathione peroxidase-like activity. Diselenide 3d, containing two morpholine substituents in the amide group, shows the highest glutathione peroxidase-like properties (Figure 11). This compound is superior to other diselenides 3a–c and selenides 2c, 2d, 2f, and 2h in activity. To the best of our knowledge, diselenide 3d is one of the most effective known reagents with glutathione peroxidase-like activity. The second most active product is compound 3c, bearing four phenyl groups. Compound 3a, containing four methyl groups, is inferior to diselenides 3b–d, however, diselenide 3a surpasses selenide 2d with the same substituents in activity. When comparing diselenides 3a–c, the tendency of increasing activity with an increasing number of carbon atoms in the amide moiety is observed.

3. Materials and Methods

3.1. General Information

The 1H (400.1 MHz), 13C (100.6 MHz), 77Se (76.3 MHz), and 15N (40.6 MHz) NMR spectra (the spectra can be found in Supplementary Materials) were recorded on a Bruker DPX-400 spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany) in CDCl3 or DMSO-d6 5–10% solutions and referred to TMS (1H, 13C), nitromethane (15N) and dimethyl selenide (77Se).
Elemental analysis was performed on a Thermo Scientific Flash 2000 Elemental Analyzer. Melting points were determined on the Kofler apparatus. The organic solvents were dried and distilled according to standard procedures.
Crystal data were collected on a Bruker D8 Venture diffractometer with MoKa radiation (λ = 0.71073) using the φ and ω scans. The structures were solved and refined by direct methods using the SHELX program set [64]. Data were corrected for the absorption effects using the multi-scan method (SADABS). Non-hydrogen atoms were refined anisotropically using the SHELX program set [64]. The Supplementary Materials contain the crystallographic data for compounds CCDC 1,834,087 (2a), 1,834,088 (2d), 1,834,089 (2f) and 1,841,340 (2i). These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif (accessed on 5 May 2022).

3.2. General Procedure for Synthesis of 2-propynamides 1a–i

A mixture of 3-trimethylsilyl-2-propynamide (0.48 mmol) and 3.5 mg K2CO3 (5 mol%) in MeOH (3.0 mL) was stirred for 0.5 h at room temperature. Then, a solution of 5% HCl (2 mL) was added and the mixture was extracted with CH2Cl2 (3 × 7 mL). The organic phase was dried over Na2SO4 and the solvent was removed under reduced pressure, giving products 2a–i.
N,N-Dicyclohexyl-2-propynamide1g. Yield: 103 mg (92%); beige powder; mp 125–127 °C.
1H-NMR (400 MHz, CDCl3): δ 1.03–1.94 (m, 18H, CH2), 2.26–2.34 (m, 2H, CH2), 3.02 (s, 1H, HC≡), 3.10–3.17 (m, 1H, CH), 4.09–4.15 (m, 1H, CH). 13C-NMR (100 MHz, CDCl3): δ 25.1 (CH2), 25.9 (CH2), 26.3 (CH2), 29.5 (CH2), 31.3 (CH2), 55.6 (CH), 59.4 (CH), 77.3 (≡CCO), 77.4 (HC≡), 152.6 (C=O).
Anal. calcd for C15H23NO (233.35): C 77.21, H 9.93, N 6.00; found: C 77.17, H 10.05, N 5.91.

3.3. General Procedure for Synthesis of (Z,Z)-bis(3-amino-3-oxo-1-propenyl) Selenides 2a–i

A mixture of powdered metallic selenium (19 mg, 0.24 mmol) and water (2.0 mL) was heated (the temperature of the water bath was 80–85 °C) and a solution of NaBH4 (28 mg, 0.74 mmol) in water (0.4 mL) was added dropwise under argon. After the dissolution of selenium and forming a colorless solution, a solution of 2-propynamide 1a–i (0.48 mmol) in MeOH (2.0 mL or 5.0 mL for compounds 1f,g) was added to a hot aqueous solution of sodium selenide. The reaction mixture was refluxed for 30 min on the water bath and cooled with cold water. The mixture was extracted with CH2Cl2 (3 × 7 mL) and the organic phase was dried over Na2SO4. The solvent was removed under reduced pressure, giving the products 2a–i. Spectral data for the products 2a–i, including X-ray analysis data, are given in the Supplementary Materials.

3.4. General Procedure for Synthesis of (Z,Z)-bis(3-amino-3-oxo-1-propenyl) Diselenides 3a–d

NaBH4 (17 mg, 0.44 mmol) was added portion-wise to a mixture of powdered metallic selenium (34 mg, 0.44 mmol), water (1.0 mL) and THF (5 mL) under argon with stirring. The mixture was stirred at room temperature for 1 h and corresponding 3-trimethylsilyl-2-propynamide (0.44 mmol) was added. The mixture was stirred at room temperature for 5 h and THF was removed by a rotary evaporator. The residue was diluted with water (1.0 mL) and extracted with CHCl3 (3 × 7 mL) and the organic phase was dried over Na2SO4. The solvent was removed under reduced pressure, giving diselenides 3a–d.
(Z,Z)-Bis(N,N-dimethyl-3-amino-3-oxo-1-propenyl) diselenide 3a. Yield: 63%, yellowish solid; mp 128–130 °C. The pure sample was obtained by dissolving the residue in THF and precipitating by the addition of CCl4.
1H-NMR (400 MHz, CDCl3): δ 3.01 (s, 6H, CH3),, 3.06 (s, 6H, CH3), 6.61 (d, 3J = 8.9 Hz, 2H, =CHCO), 7.97 (d, 3J = 8.9 Hz, 2H, SeCH=). 13C-NMR (100 MHz, CDCl3): δ 35.6, 37.3 (CH3), 115.7 (=CCO), 151.3 (SeC=, 1JSe–C = 146.1 Hz), 167.7 (C=O). 77Se-NMR (76 MHz, CDCl3): δ 571.5. 15N-NMR (40 MHz, CDCl3): δ –279.9. The 2D 15N-NMR HMBC {1H–15N} spectrum contains cross-peaks of the nitrogen atom with protons of the CH3 and =CHCO groups.
Anal. calcd for C10H16N2O2Se2 (354.17): C 33.91, H 4.55, N 7.91, Se 44.59; found: C 33.84, H 4.52, N 8.02, Se 44.48.
(Z,Z)-Bis(N-phenyl-3-amino-3-oxo-1-propenyl) diselenide3b. Yield: 50%, yellow solid; mp 202–203 °C. The pure sample was obtained by dissolving the residue in THF and precipitating by the addition of CCl4.
1H-NMR (400 MHz, d6-DMSO): δ 6.59 (d, 3J = 8.9 Hz, 2H, =CHCO), 7.08 (t, 3J = 7.8 Hz, 2H, Hp), 7.33 (dd, 3J = 7.8 Hz, 4H, Hm), 7.63 (d, 3J = 7.8 Hz, 4H, Ho), 8.01 (d, 3J = 8.9 Hz, 2H, SeCH=) 10.36 (s, 2H, NH). 13C-NMR (100 MHz, d6-DMSO): δ 119.2 (=CCO), 121.0 (Co), 123.7 (Cp), 128.9 (Cm), 138.8 (Ci), 148.3 (SeC=, 1JSe–C = 144.2 Hz), 165.2 (C=O). 77Se-NMR (76 MHz, d6-DMSO): δ 558.5. 15N-NMR (40 MHz, d6-DMSO): δ –243.7 (1JN–H = 88.7 Hz). The 2D 15N-NMR HMBC {1H–15N} spectrum contains cross-peaks of the nitrogen atom with Hm, Ho and NH protons.
Anal. calcd for C18H16N2O2Se2 (450.25): C 48.02, H 3.58, N 6.22, Se 35.07; found: C 48.00, H 3.44, N 6.01, Se 35.31.
(Z,Z)-Bis(N,N-diphenyl-3-amino-3-oxo-1-propenyl) diselenide3c. Yield: 51%, yellow solid; mp 197–198 °C. The pure sample was obtained by dissolving the residue in dichloromethane and precipitating by the addition of cold hexane.
1H-NMR (400 MHz, CDCl3): δ 6.26 (d, 3J = 9.1 Hz, 2H, =CHCO), 7.17–7.30 (m, 12H, Ho,p), 7.30–7.44 (m, 8H, Hm), 7.99 (d, 3J = 9.1 Hz, 2H, SeCH=). 13C-NMR (100 MHz, CDCl3): δ 118.3 (=CCO), 125.1–130.6 (Co,p,m), 142.1 (Ci), 152.3 (SeC=, 1JSe–C = 148.2 Hz), 167.2 (C=O). 77Se-NMR (76 MHz, CDCl3): δ 579.3.
Anal. calcd for C30H24N2O2Se2 (602.44): C 59.81, H 4.02, N 4.65, Se 26.21; found: C 59.91, H 4.05, N 4.59, Se 26.09.
(Z,Z)-Bis(3-morpholino-3-oxo-1-propenyl) diselenide3d. Yield: 70%, yellow solid; mp 193–195 °C. The pure sample was obtained by dissolving the residue in chloroform and precipitating by the addition of cold ether.
1H-NMR (400 MHz, CDCl3): δ 3.46–3.61 (m, 4H, NCH2), 3.62–3.79 (m, 12H, NCH2, OCH2), 6.61 (d, 3J = 9.1 Hz, 2H, =CHCO), 8.07 (d, 3J = 9.1 Hz, 2H, SeCH=). 13C-NMR (100 MHz, CDCl3): δ 42.3, 46.1 (NCH2), 66.8 (OCH2), 114.7 (=CCO), 152.7 (SeC=, 1JSe–C = 147.4 Hz), 166.5 (C=O). 77Se-NMR (76 MHz, CDCl3): δ 574.6. 15N-NMR (40 MHz, CDCl3): δ –264.7. The 2D 15N-NMR HMBC {1H–15N} spectrum contains cross-peaks of the nitrogen atom with proton of the =CHCO group.
Anal. calcd for C14H20N2O4Se2 (438.24): C 38.37, H 4.60, N 6.39, Se 36.04; found: C 38.34, H 4.50, N 6.32, Se 35.80.

4. Conclusions

With the goal to obtain previously unknown divinyl diselenides, containing amide groups, the reaction of sodium diselenide with 3-trimethylsilyl-2-propynamides was studied and the conditions for regio- and stereoselective addition were found. The reaction proceeded in a THF-water system at room temperature and was accompanied by desilylation.
The efficient regio- and stereoselective syntheses of (Z,Z)-bis(3-amino-3-oxo-1-propenyl) selenides 2a–i in up to 97% yields based on the nucleophilic addition of sodium selenide to 2-propynamides were developed. These are the first examples of the addition of a selenium-centered nucleophile to 2-propynamides with a terminal triple bond. The glutathione peroxidase-like activity of the obtained compounds was evaluated and the activity of selenides and diselenides was compared. It was found that diselenides 3a–d are superior to the analogous selenides 2c, 2d, 2f, and 2h with the same substituents in glutathione peroxidase-like activity. Diselenide 3d, containing two morpholine substituents in the amide group, shows the highest glutathione peroxidase-like properties. To the best of our knowledge, diselenide 3d is one of the most effective known reagents with glutathione peroxidase-like activity. When comparing diselenides 3a–c, the tendency of increasing activity with an increase in the number of carbon atoms in the amide moiety is observed.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/inorganics10060074/s1, Spectral data for the products 2a–i, including X-ray analysis data and examples of NMR spectra of the obtained compounds.

Author Contributions

Conceptualization, V.A.P.; Data curation, S.V.A.; Formal analysis, V.A.P.; Funding acquisition, V.A.P.; Investigation, M.V.A. and I.V.S.; Methodology, M.V.M.; Supervision, L.I.L.; Writing—original draft, V.A.P.; Writing—review & editing, V.A.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors thank Baikal Analytical Center SB RAS (Irkutsk, Russia) for providing the instrumental equipment.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Generation of electrophilic selenium species and nucleophilic highly reactive selenolates from organic diselenides.
Figure 1. Generation of electrophilic selenium species and nucleophilic highly reactive selenolates from organic diselenides.
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Figure 2. Organoselenium compounds including diselenides, contain amide groups and exhibit glutathione peroxidase-like activity.
Figure 2. Organoselenium compounds including diselenides, contain amide groups and exhibit glutathione peroxidase-like activity.
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Scheme 1. Synthesis of 2-propynamides 1a–i by desilylation of 3-(trimethylsilyl)-2-propynamides.
Scheme 1. Synthesis of 2-propynamides 1a–i by desilylation of 3-(trimethylsilyl)-2-propynamides.
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Scheme 2. Regio- and stereoselective synthesis of divinyl selenides 2a–i from 2-propynamides 1a–i and 77Se-NMR data.
Scheme 2. Regio- and stereoselective synthesis of divinyl selenides 2a–i from 2-propynamides 1a–i and 77Se-NMR data.
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Scheme 3. Regio- and stereoselective synthesis of divinyl diselenides 3a–d from 3-(trimethylsilyl)-2-propynamides and 77Se-NMR data.
Scheme 3. Regio- and stereoselective synthesis of divinyl diselenides 3a–d from 3-(trimethylsilyl)-2-propynamides and 77Se-NMR data.
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Figure 3. Molecular structure of compound 2a (ORTEP, 50% probability ellipsoids).
Figure 3. Molecular structure of compound 2a (ORTEP, 50% probability ellipsoids).
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Figure 4. Molecular structure of compound 2d (ORTEP, 50% probability ellipsoids).
Figure 4. Molecular structure of compound 2d (ORTEP, 50% probability ellipsoids).
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Figure 5. Molecular structure of compound 2f (ORTEP, 50% probability ellipsoids).
Figure 5. Molecular structure of compound 2f (ORTEP, 50% probability ellipsoids).
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Figure 6. Molecular structure of compound 2i (ORTEP, 50% probability ellipsoids).
Figure 6. Molecular structure of compound 2i (ORTEP, 50% probability ellipsoids).
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Figure 7. Intermolecular hydrogen bonds NH···O=C in the crystal of amide 2a.
Figure 7. Intermolecular hydrogen bonds NH···O=C in the crystal of amide 2a.
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Figure 8. Short CH···O=C contacts in the crystal of compound 2d.
Figure 8. Short CH···O=C contacts in the crystal of compound 2d.
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Figure 9. The CH···Cl bonds in the co-crystal of compound 2f with CCl4.
Figure 9. The CH···Cl bonds in the co-crystal of compound 2f with CCl4.
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Figure 10. Short CH···O=C and CH···Se contacts in the crystal of compound 2i.
Figure 10. Short CH···O=C and CH···Se contacts in the crystal of compound 2i.
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Figure 11. Studying glutathione peroxidase-like activity of compounds 3a–d and 2d (TBHP, BnSH, 0.1 mmol, deuterochloroform/CD3OD = 95/5, 0.5% mol of compounds 3a–d and 2d) by 1H-NMR monitoring.
Figure 11. Studying glutathione peroxidase-like activity of compounds 3a–d and 2d (TBHP, BnSH, 0.1 mmol, deuterochloroform/CD3OD = 95/5, 0.5% mol of compounds 3a–d and 2d) by 1H-NMR monitoring.
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Potapov, V.A.; Andreev, M.V.; Musalov, M.V.; Sterkhova, I.V.; Amosova, S.V.; Larina, L.I. 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. Inorganics 2022, 10, 74. https://doi.org/10.3390/inorganics10060074

AMA Style

Potapov VA, Andreev MV, Musalov MV, Sterkhova IV, Amosova SV, Larina LI. 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. Inorganics. 2022; 10(6):74. https://doi.org/10.3390/inorganics10060074

Chicago/Turabian Style

Potapov, Vladimir A., Mikhail V. Andreev, Maxim V. Musalov, Irina V. Sterkhova, Svetlana V. Amosova, and Lyudmila I. Larina. 2022. "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" Inorganics 10, no. 6: 74. https://doi.org/10.3390/inorganics10060074

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