Synthesis of isoxazolines from nitroalkanes via a [4+1]-annulation strategy / P. Ushakov, E. Khatuntseva, Y. Nelyubina et al. // Advanced Synthesis and Catalysis. — 2019. A novel access to isoxazolines was developed using the [4+1]‐annulation of α‐keto‐stabilized sulfur ylides with N,N‐bis(siloxy)enamines derived from aliphatic nitro compounds. The resulting 5‐keto‐substituted isoxazolines were shown to be convenient precursors of polysubstituted 3‐hydroxypyrrolidines via the one‐pot catalytic N‐O hydrogenolysis/intramolecular reductive amination sequence. Application of this approach to the formal synthesis of Merck’s potent NK1 receptor antagonist was demonstrated. [ DOI ]
Tandem deoxygenation/halogenation of n -oxides under acylation conditions: Scope and in situ ir spectroscopic study / R. S. Malykhin, I. S. Golovanov, S. L. Ioffe, A. Y. Sukhorukov // European Journal of Organic Chemistry. — 2019. — Vol. 2019, no. 26. — P. 4139–4148. Acylation of cyclic nitronates with acyl bromides produces 3‐bromomethyl‐substituted 5,6‐dihydro‐2H‐1,2‐oxazines via an unusual multi‐stage process involving deoxygenation of N‐oxide and the formation of Br2. Low‐temperature in situ ATR FT‐IR monitoring and DFT calculations revealed α‐halo‐substituted N,N‐bis(oxy)amines as key intermediates of the process. The developed method was successfully exploited in the stereoselective synthesis of pharmaceutically relevant molecules. [ DOI ]
Tandem double acylation/[3,3]-rearrangement of aliphatic nitro compounds: route to α-oxygenated oxime derivatives / Y. Antonova, Y. V. Nelyubina, A. Y. Sukhorukov et al. // Organic and Biomolecular Chemistry. — 2019. — Vol. 17, no. 24. — P. 5997–6006. [ DOI ]
A novel entry to 3,4,5-trisubstituted 2-pyrrolidones from isoxazoline-n-oxides / P. A. Zhmurov, P. Y. Ushakov, R. A. Novikov et al. // Synlett. — 2018. — Vol. 29, no. 14. — P. 1871–1874. A novel strategy for the synthesis of stereochemically defined 3,4,5-trisubstituted 2-pyrrolidones was developed. The suggested approach involves reductive domino-type recyclization of 3-aminomethyl-substituted isoxazolines as a key stage. The latter are prepared via α-C–H functionalization of readily available isoxazoline-N-oxides. [ DOI ]
Acylation of nitronates: [3,3]-sigmatropic rearrangement of in situ generated n-acyloxy,n-oxyenamines / A. O. Kokuev, Y. A. Antonova, V. S. Dorokhov et al. // Journal of Organic Chemistry. — 2018. — Vol. 83. — P. 11057–11066. Acylation of nitronates affords α-acyloxyoxime derivatives via an umpolung functionalization of the α-position. This transformation involves generation of hitherto unknown N-acyloxy,N-oxyenamines and their fast [3,3]-sigmatropic rearrangement driven by the cleavage of the weak N–O bond. The reaction has a broad scope, and it is regioselective in the case of nitronates possessing nonsymmetrically substituted α-positions. Application to the formal total synthesis of clausenamide and cis-clausenamide is presented. [ DOI ]
Cyclization of beta-chlorovinyl thiohydrazones into pyridazines: A mechanistic study / A. S. Komendantova, A. N. Fakhrutdinov, L. G. Menchikov et al. // European Journal of Organic Chemistry. — 2018. — Vol. 2019, no. 2-3. — P. 527–536. Extensive experimental and theoretical investigations on the isomerization and heterocyclizations of β‐chlorovinyl thiohydrazones derived from oxamic acid thiohydrazides and β‐chlorovinyl aldehydes were performed to elucidate the reaction mechanism of pyridazine formation. We showed that model β‐chlorovinyl thiohydrazone undergoes multiple isomerization reactions in solution induced by thione–thiol tautomerism and Z/E‐isomerization at the C=N bond. Mechanistic rationalization along with computational studies demonstrated that pyridazine is predominantly generated from the Z‐thiol isomers by 6π‐electrocyclization of the thiohydrazone‐derived 2,3‐diazatriene intermediate. The autocatalytic character of cyclization accelerated by the formation of acid was demonstrated by means of 1H NMR monitoring. [ DOI ]
Diastereoselective synthesis and profiling of bicyclic imidazolidinone derivatives bearing a difluoromethylated catechol unit as potent phosphodiesterase 4 inhibitors / V. S. Dorokhov, I. S. Golovanov, V. A. Tartakovsky et al. // Organic and Biomolecular Chemistry. — 2018. [ DOI ]
Exploiting coupling of boronic acids with triols for a ph-dependent “click-declick” chemistry / I. S. Golovanov, G. S. Mazeina, Y. V. Nelyubina et al. // Journal of Organic Chemistry. — 2018. — Vol. 83, no. 17. — P. 9756–9773. Click-like condensation of boronic acids with specifically designed triols (boronate-triol coupling) produces stable diamantane adducts in aqueous medium, which can be controllably cleaved to initial components under acidic conditions or by using boric acid as a chemical trigger. This novel “click-declick” strategy allows to create temporary covalent connections between two or more modular units that was demonstrated by the synthesis of new fluorophore-labeled natural molecules (peptides, steroids), supramolecular assemblies, modified polymers, boronic acid scavengers, solid-supported organocatalysts, biodegradable COF-like materials and dynamic combinatorial libraries. [ DOI ]
Synthesis of α-thiooximes by addition of thiols to n,n-bis(oxy)- enamines: A comparative study of s-, n-, and o-nucleophiles in michael reaction with nitrosoalkene species / A. Sukhorukov, Y. Naumovich, A. Kokuev, S. Ioffe // Synlett. — 2018. — Vol. 29, no. 10. — P. 1334–1339.
Tabolin A. A., Sukhorukov A. Y., Ioffe S. L. α-electrophilic reactivity of nitronates // Chemical Record. — 2018. — Vol. 18. — P. 1489–1500. Chemistry of covalent nitronates regarding nucleophilic addition to C=N bond is described. Various types of electrophilic activation of nitronates and stability of formed products are discussed with main attention paid to authors’ work in the area. [ DOI ]
Addition of ho-acids to n,n-bis(oxy)enamines: Mechanism, scope and application to the synthesis of pharmaceuticals / A. Y. Sukhorukov, Y. A. Naumovich, G. Ivan, S. L. Ioffe // European Journal of Organic Chemistry. — 2017. — no. 41. — P. 6209–6227. The regioselectivity of the addition of HO-acids to the activated pi-bond in N,N-bis(oxy)enamines was found to be dramatically dependent on the solvent. Mechanism investigations and quantum-chemical calculations revealed that solvent affects the reaction pathway. In basic solvents (DMF, NMP, DMSO), N,N-bis(oxy)enamines are converted into nitrosoalkenes through a Lewis base promoted process followed by the oxy-Michael addition of HO-acid. In non-polar solvents (toluene, CH2Cl2), reaction follows an acid-promoted SN' substitution of N-oxy-group via highly reactive N-vinyl-N-alkoxynitrenium species. Based on these studies, general and efficient protocols for oximinoalkylation of various HO-acids (carboxylic acids, phenols, hydroxamic, phosphoric and sulfonic acids) employing readily available N,N-bis(oxy)enamines were developed. These methods proved to be applicable for post-modification of natural molecules bearing acidic OH-groups (such as steroidal hormones, bile acids, protected amino acids and peptides) and ligands (BINOL). The resulting alpha-oxyoximes were demonstrated to be useful precursors of valuable 1,2-amino alcohol or 1,2-hydroxylamino alcohol derivatives, including the antiarrhythmic drug Mexiletine and a potent MMP inhibitor. [ DOI ]
Conjugated nitrosoalkenes as michael acceptors in carbon–carbon bond forming reactions: a review and perspective / Y. D. Boyko, V. S. Dorokhov, A. Y. Sukhorukov, S. L. Ioffe // Beilstein Journal of Organic Chemistry. — 2017. — Vol. 13. — P. 2214–2234. Despite of their chemical instability and high reactivity, conjugated nitrosoalkenes are useful intermediates in target-oriented organic synthesis. The present review deals with carbon–carbon bond forming reactions involving Michael addition to α-nitrosoalkenes with a particular focus on recent developments in this methodology and its use in total synthesis. [ DOI ]
Divergent reactivity of in situ generated metal azides: Reaction with n, n‐bis (oxy) enamines as a case study / P. A. Zhmurov, Y. A. Khoroshutina, R. A. Novikov et al. // Chemistry - A European Journal. — 2017. — Vol. 23, no. 19. — P. 4570–4578. Metal azides generated in situ by ion exchange exhibit divergent reactivity in reaction with cyclic N-alkoxy,N-siloxy-enamines. Depending on the nature of metal and the [M]/N3− ratio, addition of the azide ion to the C,C-double bond proceeds with regioselective cleavage of either exo- or endo-cyclic N−O bond leading to cyclic or open-chain α-azidooxime derivatives, respectively. Mechanistic studies in combination with solvent state FTIR spectroscopy and DFT calculations revealed that covalently bound metal azides (Co, Cu, Zn) transfer N3− anion to the C,C-double bond through a Lewis acid-assisted SN′ substitution of trialkylsilyloxy-group. More ionic metal azides (N1, Mg, Al, Sc, Ni, Yb) tend to react by initial nucleophilic attack of N3− anion on the silicon atom generating conjugated nitrosoalkenes. α-Azidooxime derivatives prepared by using the designed protocols were stereoselectively reduced to valuable 1,2-diaminoalcohols bearing up to four contiguous stereogenic centers. By reducing the α-azidooxime fragment in a stepwise manner site-selective protection and reductive amination of each of the emerging primary amino groups was achieved. [ DOI ]
Organic and hybrid systems: from science to practice / V. P. Ananikov, D. B. Eremin, S. A. Yakukhnov et al. // Mendeleev Communications. — 2017. — Vol. 27. — P. 425–438. Organic systems still dominate several traditional areas of chemical science and well-known applications, such as the synthesis of pharmaceutical compounds and drugs. However, a fascinating trend has appeared recently to combine pure organic systems into advanced molecular architectures and to create hybrid molecular systems. These interdisciplinary areas, where possible connections between organic and hybrid systems may be developed, are the focus of the present review to develop valuable practical applications. [ DOI ]
Recent advances in the synthesis and chemistry of nitronates / A. A. Tabolin, A. Y. Sukhorukov, S. L. Ioffe, A. D. Dilman // SYNTHESIS-STUTTGART. — 2017. — Vol. 49, no. 15. — P. 3255–3268. Due to their availability and versatile reactivity, nitronates have become important building blocks in the stereoselective synthesis of bioactive molecules. This short review provides a summary of recent developments on the synthesis, chemistry and applications of O-alkyl and O-silyl nitronates. [ DOI ]
Recent advances in synthesis of organic nitrogen–oxygen systems for medicine and materials science / S. G. Zlotin, A. M. Churakov, I. L. Dalinger et al. // Mendeleev Communications. — 2017. — Vol. 27, no. 6. — P. 535–546. Current trends and characteristic examples of recent advances in syntheses of practically important compounds bearing semi-polar nitrogen–oxygen bonds (NO-systems) are considered. Their applications for the preparation of pharmaceutically relevant molecules, energetic materials and some other useful products are briefly discussed with a focus on original reports published in the period 2015–2017. [ DOI ]
Synthesis and structure of n,n-dinitroamidoborane complexes / O. P. Shitov, V. A. Tartakovsky, I. S. Golovanov et al. // Chemistry - An Asian Journal. — 2017. — Vol. 12, no. 17. — P. 2237–2244. A general approach to the synthesis of borohydride complexes containing one or two dinitroamide fragments has been suggested. Based on a smooth substitution of halide in haloborane or dibromoborane complexes with N,N-dinitroamide salts, this method provides various N,N-dinitroamidoboranes complexes in good yields and in analytically pure form. By means of spectroscopic and computational methods, it was demonstrated that dinitroamidoborane complexes could form as both B,N- and B,O-isomers, which did not interconvert at ambient temperature. [ DOI ]
Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia / A. N. Semakin, A. O. Kokuev, Y. V. Nelyubina et al. // Beilstein Journal of Organic Chemistry. — 2016. — Vol. 12. — P. 2471–2477. Exhaustive Michael-type alkylations of amines and ammonia with azoalkenes (generated from α-halohydrazones) were demonstrated as an efficient approach to poly(hydrazonomethyl)amines – a novel class of polynitrogen ligands. An intramolecular cyclotrimerization of C=N bonds in tris(hydrazonomethyl)amine to the respective 1,4,6,10-tetraazaadamantane derivative was demonstrated. [ DOI ]
Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia / A. N. Semakin, A. O. Kokuev, Y. V. Nelyubina et al. // Beilstein Journal of Organic Chemistry. — 2016. — Vol. 12. — P. 2471–2477. [ DOI ]
Metal-assisted addition of a nitrate anion to bis (oxy) enamines. a general approach to the synthesis of α-nitroxy-oxime derivatives from nitronates / Y. A. Naumovich, E. B. Victoria, D. A. Sen'ko et al. // Organic and Biomolecular Chemistry. — 2016. — Vol. 14, no. 16. — P. 3963–3974. The synthesis of α-nitroxy-substituted oxime derivatives has been achieved by an unprecedented metal-assisted addition of a nitrate anion to bis (oxy) enamines, which are readily available from nitronates or nitroalkanes. The method has a broad scope and provides access to α-nitroxy-oximes and their cyclic ethers including nitroxy-substituted isoxazolines and dihydro-1, 2-oxazines, which are of interest as potential NO-donors and intermediates in the synthesis of bioactive molecules. [ DOI ]
Novel synthetic oxazines target nf-κb in colon cancer in vitro and inflammatory bowel disease in vivo / A. C. Nirvanappa, D. M. Chakrabhavi, R. Shobith et al. // PLoS ONE. — 2016. — Vol. 11, no. 9. — P. e0163209. Aberrant activation of nuclear factor kappa B (NF-κB) has been linked with the pathogenesis of several proinflammatory diseases including number of cancers and inflammatory bowel diseases. In the present work, we evaluated the anticancer activity of 1,2-oxazines derivatives against colorectal cancer cell lines and identified 2-((2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl)isoindoline-1,3-dione (API) as the lead anticancer agent among the tested compounds. The apoptosis inducing effect of API was demonstrated using flow cytometry analysis and measuring the caspase 3/7 activity in API treated cells. Based on the literature on inhibition of NF-κB by oxazines, we evaluated the effect of 1,2-oxazines against the ability of NF-κB binding to DNA, NF-κB-dependent luciferase expression and IκBα phosphorylation. We found that, API abrogate constitutive activation of NF-κB and inhibits IκBα phosphorylation in HCT116 cells. Our in silico analysis revealed the binding of oxazines to the hydrophobic cavity that present between the interface of p65 and IκBα. Given the relevance with aberrant activation of NF-κB in inflammation bowel disease (IBD), we evaluated the effect of API on dextran sulphate sodium-induced IBD mice model. The treatment of IBD induced mice with API decreased the myeloperoxidase activity in colonic extract, modulated the colon length and serum levels of pro- and anti-inflammatory cytokines such as TNF-α, IFN-γ, IL-6, IL-1β and IL-10. Furthermore, the histological analysis revealed the restoration of the distorted cryptic epithelial structure of colon in the API treated animals. In conclusion, we comprehensively validated the NF-κB inhibitory efficacy of API that targets NF-κB in in vitro colon cancer and an in vivo inflammatory bowel disease model. [ DOI ]
Sukhorukov A. Y., Sukhanova A. A., Zlotin S. G. Stereoselective reactions of nitro compounds in the synthesis of natural compound analogs and active pharmaceutical ingredients // Tetrahedron. — 2016. — Vol. 72, no. 41. — P. 6191–6281. Stereoselective reactions of nitro compounds in the synthesis of natural compound analogs and active pharmaceutical ingredients. [ DOI ]
Synthesis of 1, 4, 6, 10-tetraazaadamantane quaternary derivatives / A. Semakin, I. Golovanov, A. Y. Sukhorukov et al. // Russian Chemical Bulletin. — 2016. — Vol. 65, no. 9. — P. 2270–2277. Methods for the preparation of stable 1, 4, 6, 10-tetraazaadamantane quaternary derivatives were developed based on quaternization of a tertiary nitrogen atom in tris (β- oximinoalkyl) amines or isomeric 4, 6, 10-trihydroxy-1, 4, 6, 10-tetraazaadamantanes. This process constitutes a convenient approach to the introduction of a hydrophilic 1, 4, 6, 10- tetraazaadamantane moiety into lipophilic molecules in order to increase their solubility in water. [ DOI ]
Advances in the synthesis of 7-(3-cyclopentyloxy-4-methoxyphenyl)-hexahydro-3h-pyrrolizin-3-one (pyrromilast)–a promising agent for treatment of chronic obstructive pulmonary disease / Y. D. Boyko, A. Y. Sukhorukov, S. L. Ioffe, V. A. Tartakovsky // Russian Chemical Bulletin. — 2015. — Vol. 64, no. 6. — P. 1240–1248. The review summarizes the known approaches to diastereo-and enantioselective synthesis of 7-(3-cyclopentyloxy-4-methoxyphenyl) hexahydro-3 H-pyrrolizin-3-one (Pyrromilast), a highly active inhibitor of subtype 4B phosphodiesterase and a promising agent for treatment of chronic obstructive pulmonary disease. [ DOI ]
Novel approaches to pharmacology-oriented and energy rich organic nitrogen–oxygen systems / S. G. Zlotin, A. M. Churakov, O. A. Luk’yanov et al. // Mendeleev Communications. — 2015. — Vol. 25, no. 6. — P. 399–409. Organic compounds incorporating semi-polar nitrogen–oxygen bonds possess versatile and useful properties. For decades, nitro compounds are used as energetic materials for industrial and military applications. 1 On the other hand, some of them along with a number of other types of organic N-oxides exhibit useful biological activities associated with their capability of releasing nitric oxide (NO) under physiological conditions. [ DOI ]
Oximinoalkylamines as ligands for cu-assisted azide–acetylene cycloaddition / A. N. Semakin, D. P. Agababyan, K. Sohee et al. // Tetrahedron Letters. — 2015. — Vol. 56, no. 46. — P. 6335–6339. Oximinoalkylamines were found to be efficient ligands for acceleration of the CuAAC reaction. ‘Mixed’ oxime–triazole ligands TzβOx2 and Tz2βOx demonstrate an approximately 10-fold enhanced acceleration effect compared to commonly employed ligand TBTA using 0.1 mol % of the [Cu]/L catalytic system. The optimal catalytic system based on readily available TzβOx2 provided 1,4-disubstituted triazoles in high yields with short reaction times. [ DOI ]
Stereoselective synthesis of spirocyclic nitronates by sncl 4-promoted reaction of nitroalkenes with c-2 substituted 4-methylidene-1, 3-dioxolane / A. A. Mikhaylov, P. A. Zhmurov, A. S. Naumova et al. // Mendeleev Communications. — 2015. — Vol. 25, no. 6. — P. 449–451. SnCl4-promoted [4 + 2] cycloaddition of β-nitrostyrenes to 4-methylidene-1,3-dioxolane provides stereoselective synthesis of spirocyclic nitronates. 2-Nitrovinyl benzoate under the same conditions produces δ-substituted nitrodiene as a single E,E-isomer. [ DOI ]
Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2 / V. Srinivas, D. M. Chakrabhavi, C. Baburajeev et al. // Bioorganic and Medicinal Chemistry Letters. — 2015. — Vol. 25, no. 15. — P. 2931–2936. In the present study, we used solution combustion synthesis-bismuth oxide (Bi2O3) as catalyst for the simple and efficient synthesis of 1,2-oxazine based derivatives of 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazoles, 1-arylpiperazine and carbazoles. (4aR,8aR)-4-(4-Methoxyphenyl)-3-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)-4a,5,6,7,8,8a-hexahydro-4H-benzo[e][1,2]oxazine was found to be the most potent compound with a high degree of selectivity in inhibition towards COX2 (1.7 μM) over COX1 (40.4 μM) demonstrating the significance of 1,2-oxazine derivatives in developing COX2 specific inhibitors. Molecular docking analyses demonstrated that an isoleucine residue in the active site of COX1 is responsible for lower affinity to COX1 and increased potency towards COX2. Overall, our study reveals that the new 1,2-oxazine-based small molecules qualify as lead structures in developing COX2-specific inhibitors for anti-inflammatory therapy. [ DOI ]
Synthesis of 3-aminomethyl-4-hydroxycoumarins and their retro-mannich reaction in dimethyl sulfoxide / B. G. Milevskii, T. A. Chibisova, N. P. Solovéva et al. // Russian Chemical Bulletin. — 2015. — Vol. 64, no. 2. — P. 423–428. [ DOI ]
Synthesis of b,o,n-doped adamantanes and diamantanes by condensation of oximes with boronic acids / I. S. Golovanov, A. Y. Sukhorukov, Y. V. Nelyubina et al. // Journal of Organic Chemistry. — 2015. — Vol. 80, no. 13. — P. 6728–6736. [ DOI ]
Synthesis of tris (ɣ-oximinoalkyl) amines, new tripodal n4 ligands / V. S. Dorokhov, J. Hoimin, K. Gyumin et al. // Synthetic Communications. — 2015. — Vol. 45, no. 11. — P. 1362–1366. An original approach to the synthesis of tris(γ-oximinoalkyl)amines was proposed. The suggested synthetic sequence is based on aza-Michael addition of ammonia to methyl vinyl ketone and oximation of obtained products with hydroxylamine or O-alkhylhydroxylamines. The tris(γ-oximinoalkyl)amines may be considered as prospective N4 tripodal ligands. [ DOI ]
Дорохов В. С., Семакин А. Н., Сухоруков А. Ю. Трис(оксиминоалкил)амины - новые лиганды для катализаторов биомиметического окисления // Успехи в химии и химической технологии. — 2015. — Т. 29, № 9. — С. 36–37.
A general metal‐assisted synthesis of α‐halo oxime ethers from nitronates and nitro compounds / A. Y. Sukhorukov, M. A. Kapatsyna, T. Y. Tammy Lim et al. // European Journal of Organic Chemistry. — 2014. — no. 36. — P. 8148–8159. An approach to the synthesis of α-halo oxime ethers from readily accessible nitronates and nitro compounds via bis(oxy)enamines is reported. A key step of the strategy involves the unprecedented reaction of bis(oxy)enamines with a metal (Co, Zn, Mg, Mn) halide that acts as both a promoter and halide (Br, I, Cl) source. A variety of cyclic and acyclic ethers of α-halo oximes, including previously unavailable trimethylsilyl ethers of α-iodo oximes, have been synthesized in good-to-high yields. [ DOI ]
Synthesis and characterization of novel 1, 2-oxazine-based small molecules that targets acetylcholinesterase / A. Y. Sukhorukov, A. C. Nirvanappa, S. Jagadish et al. // Bioorganic and Medicinal Chemistry Letters. — 2014. — Vol. 24, no. 15. — P. 3618–3621. Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC50 values of 1.88, and 2.5 μM, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of −1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (log P = 2.66), suggesting a potential ability to penetrate the blood–brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer’s agents. [ DOI ]
Synthesis of tris (β, β, γ-oximinoalkyl) amines from aliphatic nitro compounds and methyl vinyl ketone / E. A. Shalamova, L. Yeosan, C. Garam et al. // Tetrahedron Letters. — 2014. — Vol. 55, no. 6. — P. 1222–1225. A general strategy for the assembly of previously unknown tris(β,β,γ-oximinoalkyl)amines from aliphatic nitro compounds and methyl vinyl ketone is described. The strategy involves N,N-bis(siloxy)enamines as key intermediates. The latter are accessible by double silylation of alkylnitro compounds. Nickel(II) and copper(II) complexes of tris(β,β,γ-oximinoalkyl)amines are prepared and structurally characterized. [ DOI ]
Synthesis, structure and dioxygen reactivity of ni (ii) complexes with mono-, bis-, tetra-and hexa-oxime ligands / Y. D. Boyko, A. Y. Sukhorukov, A. N. Semakin et al. // Polyhedron. — 2014. — no. 71. — P. 24–33. Four nickel complexes with β-(oximinoalkyl)amine ligands OxnHn containing one (Ox1H1), two (Ox2H2), four (Ox4H4) and six (Ox6H6) oxime groups were synthesized and characterized by elemental analysis, FTIR, HRMS and single crystal X-ray diffraction. β-Oximinoalkylamines OxnHn act as polydentate ligands forming five-membered chelate rings, in which nickel is coordinated with both amine and oxime nitrogen atoms. In all structurally characterized complexes, OH-groups of oximes arms are involved in hydrogen bonding with counterions (Cl−), which are located in the inner or outer coordination sphere of the nickel atom. Two new structural types of pseudo-octahedral Ni(II) β-oximinoalkylamine complexes containing two ligands per one nickel ion (Ni(Ox1H1)2Cl2 and Ni(Ox2H2)2Cl2) were identified. Dioxygen reactivity of the obtained complexes in aerobic oxidation of triphenylphosphine was studied. Bis-oxime complex Ni(Ox2H2)2Cl2 was found to be the most active promoter of triphenylphosphine oxidation among the synthesized nickel complexes. [ DOI ]
Synthesis, structure and dioxygen reactivity of ni(ii) complexes with mono-, bis-, tetra- and hexa-oxime ligands / Y. D. Boyko, A. Y. Sukhorukov, A. N. Semakin et al. // Polyhedron. — 2014. — Vol. 71. — P. 24–33. [ DOI ]
Urotropine isomer (1, 4, 6, 10-tetraazaadamantane): Synthesis, structure, and chemistry / A. N. Semakin, A. Y. Sukhorukov, Y. V. Nelyubina et al. // Journal of Organic Chemistry. — 2014. — Vol. 79, no. 13. — P. 6079–6086. The first synthesis of 1,4,6,10-tetraazaadamantane, the C3v-symmetrical structural isomer of urotropine (1,3,5,7-tetraazaadamantane), and a series of its derivatives is reported. X-ray and quantum-chemical studies revealed remarkable distinctions in structures of urotropine and “isourotropine” cations, probably arising from different types of hyperconjugation between lone electron pairs of nitrogen atoms and σ*C–N orbitals in these heterocage systems. Since substitution at bridge and bridgehead nitrogen atoms can be easily introduced, 1,4,6,10-tetraazaadamantane may be considered as a new rigid multivalent (3 + 1) scaffold for the design of functional molecules and materials. [ DOI ]
Synthesis of pde iv inhibitors. first asymmetric synthesis of two of glaxosmithkline's highly potent rolipram analogues / P. A. Zhmurov, A. Y. Sukhorukov, V. I. Chupakhin et al. // Organic and Biomolecular Chemistry. — 2013. — Vol. 11, no. 46. — P. 8082–8091. Asymmetric syntheses of two of GlaxoSmithKline's highly potent phosphodiesterase IV inhibitors CMPI 1 and CMPO 2 have been accomplished from nitroethane and simple precursors in 8 and 7 steps, respectively. The suggested synthetic strategy involves as a key stage the silylation of enantiopure six-membered cyclic nitronates. In vitro studies of PDE IVB1 inhibition revealed a significant difference in the activity of CMPI 1 and CMPO 2 enantiomers. [ DOI ]
Sukhorukov A. Y., Dilman A., Ioffe S. Six-membered cyclic nitronates in the stereoselective synthesis of natural and bioactive compounds // Chemistry of Heterocyclic Compounds. — 2012. — Vol. 48, no. 1. — P. 49–54. Of the many derivatives of nitro compounds, the six-membered cyclic nitronates 1 (or 5,6-dihydro-4H-1,2-oxazine N-oxides ) [1, 2] are at the present the most effective precursors for the preparation of stereochemically complex acyclic and heterocyclic products. [ DOI ]
Synthesis of pde ivb inhibitors. 3. synthesis of (+)-, (−)-, and (±)-7-[3-(cyclopentyloxy)-4-methoxyphenyl]hexahydro-3h-pyrrolizin-3-one via reductive domino transformations of 3-β-carbomethoxyethyl-substituted six-membered cyclic nitronates / A. Y. Sukhorukov, Y. D. Boyko, Y. V. Nelyubina et al. // Journal of Organic Chemistry. — 2012. — Vol. 77, no. 12. — P. 5465–5469. Simple three-step asymmetric and racemic syntheses of GlaxoSmithKline’s highly potent PDE IVb inhibitor 1 were developed. The suggested approach is based on reductive domino transformations of 3-β-carbomethoxyethyl-substituted six-membered cyclic nitronates, which are easily accessed by a stereoselective [4 + 2] cycloaddition of an appropriate nitroalkene to vinyl ethers. In vitro studies of PDE IVb inhibition by enantiomeric pyrrolizidinones (+)-1 and (−)-1 were performed. [ DOI ]
Synthesis of unsymmetrically substituted 4, 6, 10-trihydroxy-1, 4, 6, 10-tetraazaadamantanes via intramolecular cyclization of tris (β-oximinoalkyl) amines / A. N. Semakin, A. Y. Sukhorukov, Y. V. Nelyubina et al. // SYNTHESIS-STUTTGART. — 2012. — Vol. 44, no. 7. — P. 1095–1101. The cyclotrimerization of oximino groups in unsymmetrically substituted tris (β- oximinoalkyl) amines was studied. A general approach to the synthesis of 4, 6, 10-trihydroxy- 1, 4, 6, 10-tetraazaadamantanes containing different substituents at bridgehead carbon atoms was developed from available aliphatic nitro compounds. [ DOI ]
A general procedure for the synthesis of unsymmetrically substituted tris (β-oximinoalkyl) amines / A. N. Semakin, A. Y. Sukhorukov, S. L. Ioffe, V. A. Tartakovsky // SYNTHESIS-STUTTGART. — 2011. — no. 9. — P. 1403–1412. A first general approach to the synthesis of unsymmetrically substituted tris(β-oximinoalkyl)amines containing two or three different β-oximinoalkyl fragments has been developed. This procedure employs available aliphatic nitro compounds as starting building blocks and their silylation as the key step. This approach provides an efficient strategy for the diversity-oriented synthesis of 1,4,6,10-tetraazaadamantane derivatives. [ DOI ]
Sukhorukov A. Y., Ioffe S. L. Chemistry of six-membered cyclic oxime ethers. application in the synthesis of bioactive compounds // Chemical Reviews. — 2011. — Vol. 111, no. 8. — P. 5004–5041. Chemistry of Six-Membered Cyclic Oxime Ethers. Application in the Synthesis of Bioactive Compounds. [ DOI ]
Synthesis of pde ivb inhibitors. 1. asymmetric synthesis and stereochemical assignment of (+)-and (−)-7-[3-(cyclopentyloxy)-4-methoxyphenyl] hexahydro-3 h-pyrrolizin-3-one / A. Y. Sukhorukov, Y. D. Boyko, S. L. Ioffe et al. // Journal of Organic Chemistry. — 2011. — Vol. 76, no. 19. — P. 7893–7900. Asymmetric synthesis of GlaxoSmithKline’s highly potent phosphodiesterase inhibitor 1 has been accomplished in nine steps and 16% overall yield. The original strategy suggested involves as a key step the silylation of enantiopure six-membered cyclic nitronates 4 obtained by a highly stereoselective [4 + 2]-cycloaddition of an appropriate nitroalkene 5 to trans-1-phenyl-2-(vinyloxy)cyclohexane. Functionalization of the resulting 5,6-dihydro-4H-1,2-oxazine and subsequent stereoselective reduction of 1,2-oxazine ring in intermediate 2 furnished the pyrrolizidinone framework with the recovery of chiral auxiliary alcohol. [ DOI ]
Synthesis of phosphodiesterase ivb inhibitors 2. stereoselective synthesis of hexahydro-3h-pyrrolo [1, 2-c] imidazol-3-one and tetrahydro-1h-pyrrolo [1, 2-c][1, 3] oxazol-3-one derivatives / P. A. Zhmurov, A. A. Tabolin, A. Y. Sukhorukov et al. // Russian Chemical Bulletin. — 2011. — Vol. 60, no. 11. — P. 2390–2395. The total stereoselective synthesis of two highly potent phosphodiesterase IVb inhibitors from nitroethane, isovanillin, and ethyl vinyl ether was developed. The compounds obtained are the derivatives of hexahydro-3H-pyrrolo[1,2-c]imidazol-3-one and tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one. The strategy proposed involves silylation of six-membered cyclic nitronates as a key step leading to 5,6-dihydro-4H-1,2-oxazines with the group CH2FG (FG = N3 or OH) at the C(3) atom. [ DOI ]
The first synthesis and molecular docking studies of diastereomerically pure substituted 4-amino-7-hydroxyheptanoic acids / A. Y. Sukhorukov, S. O. Andryushkevich, G. G. Chilov et al. // Mendeleev Communications. — 2011. — Vol. 21, no. 4. — P. 183–185. Diastereoselective synthesis of 4-amino-7-hydroxyheptanoic acids 1, new GABA analogues, was performed involving reduction of C-3 functionalized 5,6-dihydro-4H-1,2-oxazines available from nitroethane. Molecular docking studies showed that amino acids of type 1 may bind to GABA transaminase, however, no inhibition was observed in the experiments with the enzyme. [ DOI ]
Synthesis of a phthalocyanine–1, 4, 6, 10-tetraazaadamantane conjugate and its activity against the human immunodeficiency virus / A. Y. Tolbin, A. Y. Sukhorukov, S. L. Ioffe et al. // Mendeleev Communications. — 2010. — Vol. 20, no. 1. — P. 25–27. A new type of phthalocyanine containing 3,5,7-trimethyl-1,4,6,10-tetraazatricyclo[3.3.1.13,7]decane-4,6,10-triol (1,4,6,10-tetraazaadamantane) within a peripheral substituent has been synthesised. Its spectral properties and interaction with human lymphoblastoma cells infected with the HIV-1BRU strain have been studied. [ DOI ]
Diastereoselective synthesis of γ-amino acids and their derivatives from nitroethane via intermediacy of 5, 6-dihydro-4h-1, 2-oxazines bearing the ch2ch (co2me) 2 substituent at c3 / A. Y. Sukhorukov, A. V. Lesiv, Y. A. Khomutova, S. L. Ioffe // SYNTHESIS-STUTTGART. — 2009. — no. 5. — P. 741–754. Stereoselective two-step reduction of available 2-[(5, 6-dihydro-4H-1, 2-oxazin-3-yl) methyl] malonates provides an efficient route to derivatives of different γ-amino acids. The mechanism and stereochemistry of the first step, reduction of the C= N bond with sodium cyanoborohydride, is discussed. [ DOI ]
Stereoselective synthesis of unnatural β-amino acids from nitroethane via 5, 6-dihydro-4h-1, 2-oxazin-3-ylacetates / A. Y. Sukhorukov, A. V. Lesiv, O. L. Eliseev et al. // SYNTHESIS-STUTTGART. — 2009. — no. 15. — P. 2578–2578. The reduction of easily available methyl 5, 6-dihydro-4H-1, 2-oxazin-3-ylacetates provides an efficient route to different diastereomerically pure unnatural β-amino acids. A two-step protocol including reduction of the C= N bond of the initial oxazine with sodium cyanoborohydride during the first step and hydrogenation of the NO bond during the second step produced the target β-amino acid esters with higher stereoselectivity than obtained with conventional catalytic hydrogenation. [ DOI ]
Synthesis of substituted 5-(3-hydroxypropyl) pyrrolidin-2-ones and pyrrolizidinones from nitroethane via c3 functionalized 5, 6-dihydro-4h-1, 2-oxazines: A novel approach to some analogues of the antidepressant rolipram / A. Y. Sukhorukov, A. V. Lesiv, Y. A. Khomutova et al. // SYNTHESIS-STUTTGART. — 2009. — no. 12. — P. 1999–2008. Easily accessible [(5,6-dihydro-4H-1,2-oxazin-3-yl)methyl]malonates 1 were converted into substituted 5-(3-hydroxypropyl)pyrrolidin-2-ones 2 and pyrrolizidinones 3, which are versatile products and intermediates for organic and bioorganic chemistry. The synthetic sequence suggested includes stereoselective two-step reduction of an oximino fragment, followed by intramolecular cyclization involving one of the CO2Me groups and decarboxylation in the last stage. The efficiency of this strategy was demonstrated by the stereoselective synthesis of pyrrolizidinone rac-4, a highly efficient analogue of antidepressant Rolipram, from nitroethane. [ DOI ]
Unusual intramolecular cyclization of tris (β-oximinoalkyl) amines. the first synthesis of 1, 4, 6, 10-tetraazaadamantanes / A. N. Semakin, A. Y. Sukhorukov, A. V. Lesiv et al. // Organic Letters. — 2009. — Vol. 11, no. 18. — P. 4072–4075. An unusual intramolecular cyclization of tris(β-oximinoalkyl)amines 1 into 4,6,10-trihydroxy-1,4,6,10-tetraazaadamantanes 2 was discovered. Compounds 2 are related to a previously unknown type of heteroadamantanes that contain the cage isomeric to urotropin. A simple three-step synthesis of tetraazaadamantanes 2 and their N-substituted derivatives 3 and 4 from ammonia and aliphatic nitro compounds via the intermediacy of available tris-oximes 1 was developed. [ DOI ]
5,6-dihydro-4h-1,2-oxazines in organic synthesis: Catalytic hydrogenation of [(5,6-dihydro-4h-1,2-oxazin-3-yl)methyl]malonates to methyl 7-oxo-1-oxa-6-azaspiro[4.4]nonane-8-carboxylates / A. Y. Sukhorukov, A. V. Lesiv, Y. A. Khomutova et al. // SYNTHESIS-STUTTGART. — 2008. — no. 8. — P. 1205–1220. [ DOI ]
Catalytic hydrogenation of 5, 6‐dihydro‐4h‐1, 2‐oxazines bearing a functionalized methylene group at c‐3 / A. Y. Sukhorukov, A. V. Lesiv, O. L. Eliseev et al. // European Journal of Organic Chemistry. — 2008. — no. 23. — P. 4025–4034. The catalytic hydrogenation of readily available methyl 2-(5,6-dihydro-4H-1,2-oxazin-3-yl)acetates 6 has been studied. Dihydrooxazines 6 without an alkoxy substituent at C-6 under mild hydrogenation conditions in methanol produce a dynamic mixture of enamines 7 and tetrahydro-2-furanamines 7′(α + β). These products can be transformed into 1,4-amino alcohols 8 under more robust hydrogenation conditions or into isomeric dihydrofurans 9 and 10 if the reduction is carried out in glacial acetic acid. Reduction of dihydrooxazines 6h,i, which possess an alkoxy substituent at C-6, under similar conditions affords pyrrolidine derivatives 12, 13 and 14. A general mechanistic scheme for the hydrogenation reaction that involves an initial N–O bond cleavage has been suggested. [ DOI ]
A convenient method for the synthesis of poly (β-hydroxyiminoalkyl) amines from aliphatic nitro compounds / A. N. Semakin, A. Y. Sukhorukov, A. V. Lesiv et al. // SYNTHESIS-STUTTGART. — 2007. — no. 18. — P. 2862–2866. A general and efficient method for the synthesis of different poly(β-hydroxyiminoalkyl)amines from aliphatic nitro compounds and amines via terminal N,N-bis(siloxy)enamine intermediates is described. [ DOI ]
A convenient procedure for the synthesis of n-acetyl-5, 6-dihydro-2h-1, 2-oxazines / P. E. Ivashkin, A. Y. Sukhorukov, O. L. Eliseev et al. // SYNTHESIS-STUTTGART. — 2007. — no. 22. — P. 3461–3468. Acetylation of 5,6-dihydro-4H-1,2-oxazines with an acetyl bromide/acetic anhydride mixture provides a general and quite simple procedure for the synthesis of N-acetyl-5,6-dihydro-2H-1,2-oxazines. [ DOI ]
A convenient procedure for the synthesis of 3-substituted 5, 6-dihydro-4h-1, 2-oxazines from nitroethane / A. Y. Sukhorukov, M. S. Klenov, P. E. Ivashkin et al. // SYNTHESIS-STUTTGART. — 2007. — no. 1. — P. 97–107. A novel and efficient four-step procedure for the synthesis of C-3-functionalised 5,6-dihydro-4H-1,2-oxazines from nitroethane is described. It includes preparation of 3-methyl-substituted six-membered cyclic nitronates, 3-(bromomethyl)-substituted 5,6-dihydro-4H-1,2-oxazines as intermediates, and nucleophilic substitution of bromine. Total yields of the target C-3-functionalised oxazines are 15-30% from nitroethane. [ DOI ]
A new course of reduction of substituted 5, 6-dihydro-4h-1, 2-oxazines to furan derivatives / A. Y. Sukhorukov, A. V. Lesiv, O. L. Eliseev et al. // Mendeleev Communications. — 2007. — Vol. 17, no. 2. — P. 122–124. [ DOI ]
Syntheses based on α-azidooximes: I. reduction of α-azidooximes / A. Y. Sukhorukov, A. N. Semakin, A. V. Lesiv et al. // Russian Journal of Organic Chemistry. — 2007. — Vol. 43, no. 8. — P. 1106–1113. Convenient procedures were developed for selective and exhaustive reduction of α-azido-oximes that were easily prepared from aliphatic nitro compounds. Nitroalkanes were shown to be convenient precursors of β-functionalized amines (1,2-diamines, iminophosphonates, β azidohydroxyl-amines, α-aminooximes). [ DOI ]
Syntheses based on α-azidooximes: Ii. preparation of 6, 7-dihydrotriazolopyrazinones from aliphatic nitro compounds / A. N. Semakin, A. Y. Sukhorukov, A. V. Lesiv et al. // Russian Journal of Organic Chemistry. — 2007. — Vol. 43, no. 8. — P. 1218–1222. α-Azidooximes readily obtained from aliphatic nitro compounds were cleanly converted into previously unknown 6,7-dihydro[1,2,3]triazolo[1,5-a]pyrazin-4(5H)-ones via [3+2]-cycloaddition to dimethyl acetylenedicarboxylate and reduction of the oximino group in forming intermediates. [ DOI ]
Petrosyants S. P., Ilyukhin A. B., Sukhorukov A. Y. Coordination polymers of scandium sulfate. crystal structures of (h2bipy)[sc (h2o)(so4) 2] 2· 2h2o and (h2bipy)[hso4]2 // Russian Journal of Coordination Chemistry/Koordinatsionnaya Khimiya. — 2005. — Vol. 31, no. 8. — P. 545–551. Compounds with the general formula Catx[Sc(H2O)z(SO4)y] · nH2O (Cat = NH4, H2Bipy (Bipy is 4,4′-bipyridine), and HEdp (Edp is ethylenedipyridine) are synthesized and identified by elemental analysis and IR spectral data. The X-ray diffraction analysis of (H2Bipy)[Sc(H2O)(SO4)2]2 · 2H2O shows that in the structure of this compound, the chains of ScO6 octahedra and SO4 tetrahedra are united to form ribbons due to the tridentate coordination of the sulfate ion. The ribbons form a framework, whose infinite cavities contain H2Bipy2+ cations. [ DOI ]
The chemistry of n,n-bis(siloxy)enamines. part 8. a general method for the preparation of α-azido oximes from aliphatic nitro compounds / A. Y. Sukhorokov, I. V. Bliznets, A. V. Lesiv et al. // SYNTHESIS-STUTTGART. — 2005. — no. 7. — P. 1077–1082. A new strategy for the synthesis of α-azido oximes from aliphatic nitro compounds via interaction of N,N-bis(silyloxy)enamines with trimethylsilylazide was realized to give the target products with good yields. [ DOI ]
