Mikhail E. Kletskii

Photo-and thermochromic spiranes. 24*. Novel photochromic spiropyrans from 2,4 -dihydroxyisophthalaldehyde

Novel series of photochromic indoline and benzoxazine spiropyrans containing ortho-placed formyl and hydroxyl groups in the benzene ring of the chromene part of the molecule have been prepared. X-ray analysis has shown that, depending on the structure of the heterocyclic component in the spiro cyclization reaction different, nonequivalent formyl groups of 2,4-dihydroxyisophthalaldehyde can participate. The synthesized compounds were used as original analogs of salicylaldehyde. The novel photochromic bispyropyrans prepared contain two different asymmetric spiro carbon atoms.

Synthesis and biological properties of nitrobenzoxadiazole derivatives as potential nitrogen(ii) oxide donors: SOX induction, toxicity, genotoxicity, and DNA protective activity in experiments using Escherichia coli-based lux biosensors

Dihetaryls containing superelectrophilic and π-excessive heterocycles were synthesized by the nucleophilic aromatic substitution and cycloaddition. The structures of the compounds and the mechanism of 1,3-N-oxide tautomerism were studied by NMR spectroscopy, X-ray diffraction, and quantum chemical methods. The ability of these compounds to initiate SOX induction, which is probably due to the in vivo generation of nitrogen(ii) oxide, was quantified using genetically engineered E. coli-based lux biosensors. 7-(1-Methylpyrrol-3-yl)-4,6-dinitrobenzofuroxan is the most active inducer, which is an order of magnitude more effective than nitroglycerin used as the reference compound. The absence of toxicity was established using the E. coli MG 1655 biosensor (pXen7-lux). The DNA protective effect of this leading compound was confirmed using the E. coli MG 1655 biosensor (pRecA-lux).

[3+2] Cycloaddition Reactions to Indolyl- and Pyrrolyl Derivatives of Dinitrobenzofurazan

The reactions of 4-chloro-5,7-dinitro-4-benzofurazan with indole and pyrrole derivatives, occurring by SNAr–SEAr mechanism, led to the formation of dihetaryls with intramolecular charge transfer. A method was developed for the annelation of pyrrole and dihydropyrrole ring to nitrobenzofurazan fragment by adding unstabilized azomethine ylide to the С=С bond of dinitrobenzofurazan. The structure of nitrobenzofurazan derivatives was studied by X-ray structural analysis, NMR spectroscopy, and quantum-chemical calculations using ab initio and DFT methods.

Competitive Ring Expansion of Azetidines into Pyrrolidines and/or Azepanes

Azetidines fitted with a 3-hydroxypropyl side chain at the 2-position undergo intramolecular N-alkylation after activation of the primary alcohol, and the produced 1-azonia-bicyclo[3.2.0]heptane is opened by different nucleophiles (cyanide, azide, or acetate anions) to produce mixtures of ring expanded pyrrolidines and azepanes, or a unique type of compound. Distribution of produced five- or seven-membered rings depends on the substitution pattern on the azetidine ring and on its side chain, together with the nature of the nucleophile used in the expansion process. Observed regioselectivities for nucleophilic opening are rationalized by quantum mechanical DFT calculations and are in good agreement with experimental results.

Regio- and stereoselective synthesis of α-hydroxy-β-azido tetrazoles

Unreported α-hydroxy-β-azido tetrazoles were prepared in one step from readily available α,β-epoxy nitriles. This reaction involves a dibutyltin oxide-catalyzed cycloaddition of the nitrile reacting with TMSN3 leading to the tetrazole moiety, and opening of the epoxide by the azide anion. High levels of regio- and stereoselectivity are obtained in this reaction and are discussed, also by means of quantum mechanical DFT calculations. The azido group in these compounds could be uneventfully reduced to the corresponding amine thus leading to an α-hydroxy-β-amino tetrazole, surrogate of the corresponding carboxylic acid, while reaction with triphenylphosphine led to propargylic amines.

Synthesis of the first 13-nitroaryl derivatives of 8-acetonylberberine

For the first time a method for the synthesis of 8-acetonylberberine 13-nitroaryl derivatives has been developed comprising a one-pot reaction of berberine, acetone, and neutral aromatic electrophiles (picryl chloride, 4-chloro-7-nitrobenzofurazan, 4-chloro-5,7-dinitrobenzofurazan). It was found that the reaction of 8-acetonylberberine with these chloronitroarenes does not lead to the formation of the target compounds.

Quantum-chemical and NMR study of nitrofuroxanoquinoline cycloaddition

Using DFT/B3LYP and ab initio RHF quantum-chemical calculations in the triple-zeta basis set 6-31++G** the endo and exo cycloaddition mechanism for the interaction of ethyl vinyl ether, trimethylsilyloxybutadiene, or cyclopentadiene with 5-nitro-7,8-furoxanoquinolines was studied in details. Considering that both in solutions and crystals nitrofuroxanoquinoline exists as an inseparable mixture of two N-oxide tautomers, all cycloaddition processes were studied for both of them. The studied mechanisms practically do not depend on the location of the exocyclic oxygen atom in nitrofuroxanoquinoline molecule. At the first step of all reactions the conjugated nitroarene fragments C=C–N=O react with nucleophilic reagents following the mechanism of endo-[4+2] cycloaddition with inverse electronic demand. Further (in the cases of trimethylsilyloxybutadiene and cyclopentadiene) endo-[4+2] cycloadducts recyclize spontaneously according to the mechanism of [3,3] sigmatropic rearrangement into more thermodynamically stable, experimentally detected endo-[2+4] cycloadducts. Both endo-[4+2] and endo-[2+4] cycloadducts obtained from cyclopentadiene and nitrofuroxanoquinoline have been experimentally isolated and characterized. For this case, the kinetic and activation parameters of [4+2] → [2+4] transformation have been studied by 1H NMR method, which have shown an excellent agreement with quantum-chemical results. In all cases the exo processes are one-step reactions, less favorable kinetically than their endo competitors.

Mechanism of Thiol-Induced Nitrogen(II) Oxide Donation by Furoxans: a Quantum-Chemical Study

Quantum-chemical calculations according to DFT with UB3LYP functional in the 6-311++G** basis set, and accounting for solvation effects by the polarized continuum method were used to study the mechanisms of thiol-induced fragmentation of unsubstituted and annulated furoxans with the elimination of nitrogen(II) oxide. A preference for NO formation according to the radical mechanism involving an attack by sulfanyl radical (HS˙) on the carbon atom bonded to the N-oxide group was demonstrated for all systems. Anionic mechanisms involving HS– anions were not feasible in any of the cases due to high endothermic effects.

Intramolecular π-complexes based on nitroaryl derivatives of furotroponimine: structure and stereodynamics

Neutral aromatic electrophiles, such as trinitrobenzene and dinitrobenzofuroxane, covalently bound to the furotroponimine moiety form intramolecular through-space charge-transfer π-complexes both in solution and in the crystalline state. The kinetic and activation parameters of stereodynamic processes were determined by dynamic NMR spectroscopy. These parameters provide quantitative estimates of the kinetic stability of the p-complexes. The electronic and geometric characteristics of the π-complexes were calculated by the B3LYP/6-31G** method.

Thiol-induced nitric oxide donation mechanisms in substituted dinitrobenzofuroxans

The goal of present work is the quantum chemical study of NO donation mechanism in dinitrobenzofuroxan aryl derivative. Mechanisms of its structural non-rigidity (1,3-N-oxidic and Boulton-Katritzky rearrangements) and minimum energy pathways of NO donation under the action of sulfanyl radical SH· were considered in details. DFT calculations were performed using B3LYP and UB3LYP functionals in the 6-311++G(d,p) basis set. Obtained results showed that a high experimentally proven NO-donor activity of dinitrobenzofuroxan aryl derivative is connected with its existence in the form of mixture of 1-N-oxide and 3-N-oxide, where the 3-N-oxide is more reactive towards SH·. The thiol-induced low-barrier mechanism of NO-donation is a result of para-aminophenyl substituent availability in position 7 of dinitrobenzofuroxan.