M. M. Shakirov

Efficient synthesis of the first betulonic acid-acetylene hybrids and their hepatoprotective and anti-inflammatory activity.

The Sonogashira reaction can be applied for the preparation of acetylenic derivatives of betulonic acid where the triterpenoid moiety can serve as either the halo- or the acetylenic component. This reaction opened access to the first derivatives of betulonic acid containing either the arylethynyl (C[triple bond]C-Ar(Het) or the ethynyl (C[triple bond]CH) moieties. From the fundamental perspective, this work illustrates the possibility of selective Pd-catalyzed cross-coupling at terminal acetylenes in the presence of a terminal alkene. Hepatoprotective and anti-inflammatory properties of selected acetylenic derivatives of betulonic acid were investigated using the CCl4-induced hepatitis and carrageenan-induced edema models, respectively.

Synthesis of new chiral N-substituted fused pyrazoles and pyrazolinols

Abstract Treatment of β-diketones and the corresponding β-enaminoketones, having modified carane (2-ethyl-6,6-dimethylbicyclo[3.1.0]hexane) and p-menthane (3-ethyl-1-isopropylcyclopentane) skeletons, with aryl- and alkylhydrazines results in regioselective formation of N-substituted pyrazoles or stable pyrazolinols depending on the nature of the substituent at the hydrazine nitrogen.

Synthesis of Betulonic Acid Derivatives Containing Amino-Acid Fragments

New derivatives of betulonic acid containing on C-28 fragments of amino acids or their methyl esters were prepared as potential biologically active agents.

Molecular complexes of octafluoronaphthalene with acyclic and heterocyclic sulfur–nitrogen compounds

Abstract Mismatched molecular 1:1 complexes were prepared from C10F8 and sulfur diimides ArNSNAr 1 and ArNSN–SiMe3 2, 3 (1, 2: Ar=2,6–dimethylphenyl; 3: Ar=phenyl). In the case of 2, the complexation is accompanied by the unexpected cyclization of 2 into 7-methyl-2,1-benzisothiazole 4. The X-ray molecular structures of C10F8·1, C10F8·3 and C10F8 are presented; in C10F8·4 the 7-methyl-2,1-benzisothiazole 4 is highly disordered. The complexes provide very rare examples of markedly bent (C10F8·1), polyheteroatom (C10F8·3) and heterocyclic (C10F8·4) molecules involved in non-covalent arene-polyfluoroarene π-stacking interactions.

Synthesis of 30-amino derivatives of lupane triterpenoids

New derivatives of betulin and betulinic acid containing various amines on C-30 that are of interest as potentially biologically active agents were prepared.

A polyfluoroaromatic tellurium–nitrogen compound: synthesis and properties of 4,5,6,7-tetrafluoro-2λ4δ2,1,3-benzotelluradiazole

4,5,6,7-Tetrafluoro-2λ4δ2,1,3-benzotelluradiazole compound 2 (and a 15N-enriched sample) is synthesized by treating TeCl4 with the corresponding diamine 4 in the absence of HCl acceptors. Some of its properties, .e.g. high volatility, facile hydrolysis and vibrational frequencies, are experimentally determined.

SYNTHESIS AND STUDY OF MUTAGENIC PROPERTIES OF LUPANE TRITERPENOIDS CONTAINING 1,2,3-TRIAZOLE FRAGMENTS IN THE C-30 POSITION

New derivatives of betulin, betulinic acid methyl ester, and their acetate analogs containing 1,2,3-triazole fragments in the C-30 position were synthesized. It was shown using the Ames test that 30-azidolup-20(29)-enes and 3β,28-diacetoxy-30-(4-R-1,2,3-triazol-1-yl)lup-20(29)-enes did not exhibit mutagenic properties.

Interaction of 1,3,2,4-Benzodithiadiazines and Their 1-Se Congeners with Ph3P and Some Properties of the Iminophosphorane Products

Interaction between Ph(3)P and 1,3,2,4-benzodithiadiazine (1); its 6,7-difluoro (2), 5,6,8-trifluoro (3) and 5,6,7,8-tetrafluoro (4) derivatives; and 5,6,8-trifluoro-3,1,2,4-benzothiaselenadiazine (5) proceeded via a 1:1 condensation to give Ph(3)P═N-R iminophosphoranes (1a-5a, R = corresponding 1,2,3-benzodichalcogenazol-2-yls), which are inaccessible by general approaches based on the Staudinger and Kirsanov reactions. In contrast, neither Ph(3)As nor Ph(3)Sb reacted with 1 and 4. Molecular structures of 1a-5a and 5 were confirmed by X-ray diffraction (XRD). The crystals formed by chiral molecules of 2a-5a were racemic, whereas the crystal of 1a was formed by a single enantiomer. In all of the Ph(3)P═N-R derivatives, one of the Ph rings is oriented face-to-face to the hetero ring, R. Upon heating to ∼120 °C in squalane (1a, 3a, 4a) or dissolving in chloroform at ambient temperatures (1a, 2a, 4a), the Ph(3)P═N-R derivatives generated the 1,2,3-benzodithiazolyls (1b-4b, respectively) whose identity was confirmed by electron paramagnetic resonance (EPR). 2,1,3-Benzothiaselenazolyls 5b and 6b were detected by EPR as the main paramagnetic products of solution thermolysis of 5 and its 5,6,7,8-tetrafluoro congener (6), respectively. Passing a chloroform solution of 4a through silica column unexpectedly gave 5-6-6-6 tetracyclic (9) and 6-10-6 tricyclic (10) sulfur-nitrogen compounds, which were characterized by XRD.

Synthetic transformations of higher terpenoids: XXIV. Synthesis of cyanoethyl derivatives of lupane triterpenoids and their transformation into 1,2,4-oxadiazoles

Cyanoethylation of lupane triterpenoids was performed. Amide oximes of 3β-O-(2-cyanoethyl)-betulinic acid methyl ester and 3β-O-acetyl-28-O-(2-cyanoethyl)betulin and the corresponding O-[2-(1,2,4-oxadiazol-3-yl)ethyl] lupane derivatives were obtained.

Synthesis of 1H-1,2,3-triazole linked aryl(arylamidomethyl) - dihydrofurocoumarin hybrids and analysis of their cytotoxicity.

A series of 2-(4-R-triazolyl)substituted 3-oxo-2,3-dihydrofurocoumarins have been synthesized by a regioselective cycloaddition of 2-azidooreoselone 1 or 2-azido-9-[(4-methylpiperazin-1-yl)methyl]oreoselone 2 with various alkynes in the presence of Cu(II)/ascorbate in water/methylene chloride reaction medium. The structure of 2-azidooreoselone was established by X-ray structure analysis. The cytotoxicity of 2-substituted dihydrofurocoumarins was determined against three cancer cell lines (CEM-13, MT-4, U-937) using the conventional MTT assays. Among the tested molecules, most of the analogs displayed better cytotoxic activity then the parent natural furocoumarin peucedanin 3. The activity and selectivity to the cell line increased even further in the series of 2-(4-{2,3-dihydrobenzo[b][1,4]dioxine}triazolyl)-3-oxo-2,3-dihydrofurocoumarins and 2-(4-aryltriazolyl)-3-oxo-2,3-dihydrofurocoumarins having the (4-methylpiperazin-1-ylmethyl) substituent in the 9-th position. The most active compound 20 contain the 4-hydroxy-3-methoxybenzamidomethyl substituent in the 4-th position at the triazole ring of 2-(triazol-1-yl)dihydrofurocoumarins. The obtained 2-triazolyl substituted dihydrofurocoumarins were studied as inhibitors of phosphodiesterase (PDE-4B) using docking experiments. As a result of virtual screening 3 compounds are selected based on minimum binding energy. The interactions of the most active compound and amino acid residues in the binding site were studied.