- Construction of Saturated Oxazolo[3,2-b][1,2]oxazines via Tandem [3+2]-Cycloaddition/[1,3]-Rearrangement of Cyclic Nitronates and Ketenes
-
Reaction of six-membered cyclic nitronates with disubstituted ketenes affords hitherto unknown saturated oxazolo[3,2-b][1,2]oxazines possessing up to four contiguous stereogenic centers. The process involves a tandem of [3+2]-cycloaddition across the Ca? O bond of ketene, followed by a spontaneous [1,3]-rearrangement of transient vinylidene-substituted bicyclic nitrosoacetals. DFT calculations of the mechanism suggest that the [1,3]-O,C-shift proceeds through a recyclization of a biradical intermediate formed by an unusually mild homolytic cleavage of the N-O bond. The resulting products can be utilized as precursors of other fused 1,2-oxazines derivatives, in particular 1,2-oxazino-1,2,4-triazin-3-ones.
- Malykhin, Roman S.,Golovanov, Ivan S.,Nelyubina, Yulia V.,Ioffe, Sema L.,Sukhorukov, Alexey Yu.
-
p. 16337 - 16348
(2021/12/02)
-
- Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells
-
Constitutive activation of NF-κB is associated with proinflammatory diseases and suppression of the NF-κB signaling pathway has been considered as an effective therapeutic strategy in the treatment of various cancers including hepatocellular carcinoma (HCC). Herein, we report the synthesis of 1,2 oxazines and their anticancer potential. The antiproliferative studies presented 3-((4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)methyl)-4-phenyl-4,4a,5,6,7,7a-hexahydrocyclopenta [e][1,2]oxazine(3i) as a lead cytotoxic agent against HCC cells. Flow cytometric analysis showed that 3i caused a substantial increase in the subG1 cell population. Annexin-V-FITC-PI staining showed a significant increase in the percentage of apoptotic cells on treatment with 3i. Transfection with p65 siRNA significantly reduced the 3i induced DNA fragmentation indicating that 3i may primarily mediate its proapoptotic effects by abrogating the NF-κB signaling. In addition, treatment of HCC cells with 3i decreased the DNA binding ability of NF-κB and NF-κB-dependent luciferase expression. Taken together, this report introduces 1,2-oxazine that potently targets the NF-κB signaling pathway in HCC cells.
- Somu, Chaithanya,Mohan, Chakrabhavi Dhananjaya,Ambekar, Sachin,Dukanya,Rangappa, Shobith,Baburajeev,Sukhorukov, Alexey,Mishra, Srishti,Shanmugam, Muthu K,Chinnathambi, Arunachalam,Awad Alahmadi, Tahani,Alharbi, Sulaiman Ali,Basappa,Rangappa, Kanchugarakoppal S.
-
-
- Synthesis of α-Thiooximes by Addition of Thiols to N, N -Bis(oxy)-enamines: A Comparative Study of S-, N-, and O-Nucleoa-philes in Michael Reaction with Nitrosoalkene Species
-
Nucleophilic addition of thiols to N, N -bis(oxy)enamines (nitrosoalkene acetals) produce valuable α-thiooximes in a highly efficient manner. The reaction was found to be solvent-dependent, likely because of distinct mechanisms operating in nonpolar and basic solvents (involving either Bronsted acid or Lewis base catalysis). By performing a series of competition experiments, the relative reactivity of S-, N-, and O-nucleophiles in reaction with N, N -bis(oxy)enamines was determined for the first time. Interestingly, the relative nucleophilicity was found to be highly dependent on the solvent, which allows regioselective control of these reactions by using an appropriate medium.
- Naumovich, Yana A.,Kokuev, Aleksandr O.,Sukhorukov, Alexey Yu.,Ioffe, Sema L.
-
supporting information
p. 1334 - 1339
(2018/04/19)
-
- Addition of HO-Acids to N,N-Bis(oxy)enamines: Mechanism, Scope and Application to the Synthesis of Pharmaceuticals
-
The regioselectivity of the addition of HO-acids to the activated π bond in N,N-bis(oxy)enamines has been found to be dramatically dependent upon the solvent. Mechanistic investigations and quantum-chemical calculations revealed that solvent affects the reaction pathway. In basic solvents (DMF, NMP, DMSO), N,N-bis(oxy)enamines were converted into nitrosoalkenes by a Lewis base promoted process followed by oxy-Michael addition of the HO-acid. In non-polar solvents (toluene, CH2Cl2), the reaction occurs by an acid-promoted SN′ substitution of the N-oxy-group via a highly reactive N-vinyl-N-alkoxynitrenium species. Based on these studies, general and efficient protocols for the 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 to the 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 α-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 matrix metalloproteinase inhibitor.
- Naumovich, Yana A.,Golovanov, Ivan S.,Sukhorukov, Alexey Yu.,Ioffe, Sema L.
-
p. 6209 - 6227
(2017/11/15)
-
- Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase
-
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 concen
- Sukhorukov, Alexey Yu.,Nirvanappa, Anilkumar C.,Swamy, Jagadish,Ioffe, Sema L.,Nanjunda Swamy, Shivananju,Basappa,Rangappa, Kanchugarakoppal S.
-
p. 3618 - 3621
(2014/07/22)
-
- A convenient procedure for the synthesis of 3-substituted 5,6-dihydro-4H-1,2-oxazines from nitroethane
-
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. Georg Thieme Verlag Stuttgart.
- Sukhorukov, Alexey Yu.,Klenov, Michael S.,Ivashkin, Pavel E.,Lesiv, Alexey V.,Khomutova, Yulya A.,Ioffe, Sema L.
-
-
- New C-C coupling reaction of cyclic nitronates with carbon nucleophiles. Umpolung of the conventional reactivity of nitronates
-
Cyclic six-membered nitronates 1 are involved in diastereoselective C-C coupling reactions with various nucleophiles in the presence of either catalytic or stoichiometric amounts of TBDMSOTf to give the previously unknown N-siloxytetrahydrooxazines. The i
- Smirnov, Vladimir O.,Ioffe, Sema L.,Tishkov, Alexander A.,Khomutova, Yulia A.,Nesterov, Ivan D.,Antipin, Michael Yu.,Smit, William A.,Tartakovsky, Vladimir A.
-
p. 8485 - 8488
(2007/10/03)
-
- 2-Silyloxy-1,2-oxazines, a New Type of Acetals of Conjugated Nitroso Alkenes
-
3-Alkyl-substituted 1,2-oxazine N-oxides 2 can be selectively transformed into 2-silyloxy-1,2-oxazines 1 upon treatment with silylating reagents. In the solid state derivatives 1 adopt a chair conformation with the pyramidal nitrogen atom, whereas in solu
- Tishkov, Alexander A.,Lesiv, Alexey V.,Khomutova, Yulya A.,Strelenko, Yury A.,Nesterov, Ivan D.,Antipin, Michael Yu.,Ioffe, Sema L.,Denmark, Scott E.
-
p. 9477 - 9480
(2007/10/03)
-