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A smooth synthesis of 4H-[1,2,3]triazolo[4,5-c][1,2,5]oxadiazole 5-oxide 1 and its energetic salts (ammonium, hydroxylammonium, guanidinium, triaminoguanidinium) is reported. The compounds synthesi...

Quaternary 4-(2-naphthyl)pyridinium salts with various N-substituents were synthesized. The structure of these salts was determined by X-ray crystallography. The self-assembly of the salts with cavitand molecules – β- and γ-cyclodextrins and cucurbit[7,8]urils – in aqueous solutions was studied by electronic spectroscopy and 1H NMR spectroscopy, including spectrophotometric, fluorescence, and 1H NMR titrations. The formation of inclusion complexes of different stoichiometry and stability, was observed, depending on the structure of N-substituent in the quaternary salt and the cavitand nature and cavity size. The complex formation with cucurbiturils results in considerable changes in the absorption and fluorescence spectra of naphthylpyridine derivatives. Motion of the guest molecules in the cavitand cavities was detected. The X-ray diffraction study was carried out for two polymorphs of 2 : 1 complexes formed by betaine type naphthylpyridine and cucurbit[8]uril, in which the cavitand was located either above the naphthalene residues of a dimeric pair of guest molecules or above the centers of their conjugated moieties.

A two-step one-pot condensation for the synthesis of previously inaccessible 2,6-disubstituted 2,3a,4a,6,7a,8a-hexaazaperhydrocyclopenta[def]fluorene-4-thioxo-8-ones from simple reagents [5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one, paraformaldehyde and amines] was developed. The structure, antimicrobial, and anticancer activity of a number of synthesized compounds were studied.

The complex formation of thiamonomethine cyanine dyes bearing two N-ammoniohexyl or two N-ethyl substituents with cucurbit[5,7]urils (CB[5,7]) in aqueous solutions was studied by electronic and 1H NMR spectroscopy, including spectrophotometric, fluorescence, and 1H NMR titration methods. It was found that CB[5] forms external complexes with the dyes, while CB[7] forms internal (inclusion) complexes of 1:1 and 1(dye):2(CB[5,7]) composition. The complexation with CB[5,7] changes the absorption spectra of cyanine dyes and induces a considerable fluorescence enhancement. The stability constants of the complexes were determined (logK1:1 varies in the range from 3.53 to more than 6, and logK1:2 varies in the range from 3.5 to 4.32). The dye with ammoniohexyl substituents forms more stable complexes owing to hydrogen bond formation between the NH3+ groups and the carbonyl groups of the CB[5,7] portals. The structure of supramolecular complexes was confirmed by quantum chemical calculations.

4,5-Diarylisoxazoles are potent antiproliferative tubulin-targeting agents. Their isomeric 3,4-diaryl-5-unsubstituted isoxazoles are hardly accessible. The synthesis of 3,4-diaryl-5-unsubstituted isoxazoles 13 was designed based on a condensation of arylbenzaldehydes, arylnitromethanes, and ethoxycarbonylmethylpyridinium bromide followed by a selective one-step transformation of intermediate 3,4-diaryl-5-ethoxycarbonyl-4,5-dihydroisoxazole 2-oxides 8. The orientation of aryl rings in relation to isoxazole heterocycle was confirmed by X-ray crystallography. Targeted compounds were evaluated for antimitotic microtubule destabilizing activity using a phenotypic sea urchin embryo assay. 3-(4-Methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)isoxazole 13e and 13h with a single methoxy substituent were the most potent. Compound 13e showed strong cytotoxicity in NCI60 screen with GI50 for NCI-H522 human lung cancer cell line of 0.023 μM.

The convenient regioselective scalable synthesis of 3,4-diaryl-5-carboxy-4,5-dihydroisoxazole 2-oxides was developed based on a condensation of simple starting materials (arylbenzaldehydes, arylnitromethanes, and ethoxycarbonylmethylpyridinium bromide) under mild conditions. The obtained synthons can be applied for the synthesis of 3,4-diarylisoxazole derivatives capable of suppressing malignant growth.

New 4-pyridine-derived styryl dyes having an ammonioalkyl N-substituent in the pyridine moiety and various substituents in the benzene moiety were synthesized. The formation of pseudodimeric complexes of ammonioalkyl styryl dye derivatives with 18-crown-6-containing styryl dyes of the 4-pyridine, 4-quinoline, and 2-benzothiazole series was studied by 1H NMR in MeCN-d3. It was found that the stability of supramolecular complexes is mainly determined by the monotopic interaction of the ammonioalkyl group with the crown ether moiety via hydrogen bonding. The components of pseudodimeric complexes undergo stereospecific cross-[2+2] photocycloaddition reaction to give unsymmetrical rctt isomers of cyclobutane derivatives owing to the syn-head-to-tail arrangement of components in the initial complex. The efficiency of photoreaction is affected by the N-substituent length, the nature of the substituent in the benzene ring of the ammonioalkyl component, and the nature of the heterocyclic residue of the crown-containing component. The structures of dyes, pseudodimeric complexes, and the cyclobutane derivative were studied by X-ray diffraction.

Dienones (ketocyanine dyes) containing two aza-18-crown-6 ether residues were synthesized. The complex formation of these dyes with the EtNH3+ and +H3N(CH2)nNH3+ ions (n = 2–10, 12) in MeCN was studied by electronic and 1H NMR spectroscopy, including spectrophotometric and 1H NMR titration. It was found that homoditopic bis-azacrown dienones and alkanediammonium ions with a short polymethylene chain form 1:1, 2:2, and 1:2 complexes, whereas alkanediammonium ions with a long polymethylene chain form only pseudocyclic 1:1 complexes. The stability constants of the resulting complexes were determined (logK1:1 varies in the range from 2.74 to 5.62 [M–1], logK2:2 = 2.1 [M–1], and logK1:2 varies in the range from 2.03 to 2.96 [M–1]). The most stable complexes are formed by diammonium ions with a long polymethylene chain owing to simultaneous binding of both NH3+ groups to the azacrown ether residues of the dye. The structure of supramolecular complexes was confirmed by quantum chemical calculations.

The synthesis of new styryl dyes derived from 4-pyridine and 4-quinoline and having an ammonioalkyl N-substituent and benzocrown ether moieties of different sizes and with different sets of heteroatoms was developed. Spontaneous "head-to-tail" dimerization of these dyes via the formation of numerous hydrogen bonds between the terminal NH3(+) groups and crown ether moieties was detected in MeCN solutions. The stability constants of the dimeric complexes having pseudocyclic structure were studied by (1)H NMR titration. The most stable complexes (log Kd up to 8.2) were found in the case of dyes with the 18-crown-6 ether moiety, which is most complementary for binding a primary ammonium group. Stacking interaction of the conjugated systems in the dimeric complexes contributes to their stability to a much lesser extent. In dimeric complexes, the ethylene bonds of the dyes are preorganized for stereospecific [2 + 2] photocycloaddition (PCA) induced by visible light. PCA yields only rctt isomers of bis-crown-containing cyclobutane derivatives. The dyes were studied by X-ray diffraction; it was found that the dimeric arrangement is also retained in the crystalline state. The possibility of topochemical PCA of the dyes in single crystals without their destruction was demonstrated. The possibility of retro-PCA of the obtained cyclobutane derivatives to give the starting dyes was shown. The elucidated regularities of PCA can be used to fabricate optical data recording systems based on ammonioalkyl derivatives of crown ether styryl dyes.

A novel complex of Sc(III) with pyrazole substituted 1,3-diketone (1,3-bis(1,3-dimethyl-1H-pyrazol-4-yl)-1,3-propanedione) was synthesized and characterized by X-ray diffraction, nanotechnology-assisted laser desorption/ionisation time-of-flight mass spectroscopy (NALDI-TOF-MS) and NMR spectroscopy, including 45Sc NMR. The first sample of organic light-emitting diode (OLED) based on heteroaromatic Sc(III) 1,3-diketonate as an active layer was fabricated and tested. The maximum intensity of yellowish-green electroluminescence (530–560 nm) was equal to 40 cd/m2 and turn-on voltage was about 4.5 V. Further device modification and ligand structure optimization can lead to a better performance of such materials for OLEDs.

Novel 2-benzothiazole-, 4-pyridine-, and 2- and 4-quinoline-based styryl dyes containing an N-methylbenzoaza-15(18)-crown-5(6)-ether moiety were synthesized. A detailed electronic spectroscopy study revealed high performance of these compounds as optical molecular sensors for alkali and alkaline-earth metal cations. They were shown to considerably surpass analogous chromoionophores based on N-phenylaza-crown ethers regarding both the ionochromism and the cation-binding ability. In addition, they act as fluorescent sensors for the metal cations by demonstrating cation-triggered emission. Upon complexation with Ba(2+), the fluorescence enhancement factor reaches 61. The structural features of dyes and their metal complexes were studied by NMR spectroscopy and X-ray diffraction. The high degree of macrocycle preorganization was found to be one of the factors determining the high cation-binding ability of the sensor molecules based on N-methylbenzoaza-crown ethers.

A series of 3,7-diaryl-6,7-dihydroisothiazolo [4,5-b]pyridin-5(4 H )-ones 8 and 9 was synthesized by multicomponent condensation of 3-aryl-5-isothiazolecarboxylic acid esters 4a – f with aromatic (or thienyl) aldehydes 7 and Meldrum's acid in an acidic medium. The targeted compounds were evaluated for their antimitotic microtubule destabilizing activity using in vivo phenotypic sea urchin embryo model and in vitro human cancer cell-based assays. Selected dihydroisothiazolopyridinones altered sea urchin egg cleavage in 2–10 nM concentrations together with significant cytotoxicity against cancer cells including chemoresistant cell lines (IC 50 in submicromolar – low nanomolar concentration range). Both approaches confirmed antimitotic microtubule destabilizing mechanism of action of the izothiazole derivatives. Structure-activity relationship study determined the importance of p -methoxybenzene A-ring for the antiproliferative effect. The most potent compound 9b containing p -methoxybenzene A-ring and thiophene B-ring caused mitotic arrest and disintegration of cell microtubules.

Analogues of the bioactive natural alkoxynaphthalene pycnanthulignene D were synthesized by an efficient method. The starting plant allylalkoxybenzenes (1) are easily available from the plant essential oils of sassafras, dill, and parsley. The target 1-arylalkoxynaphthalenes (5) exhibited antiproliferative activity in a phenotypic sea urchin embryo assay.

Reactions of 4-bromo-5-nitrophthalonitrile (BNPN) with enolates of alkyl 4-R-2,4-dioxobutanoates gave alkyl 3-acyl-5,6-dicyanobenzofuran-2-carboxylates, 4-(2-R-2-oxoethyl)-5-nitrophthalonitriles, or 3-acyl-1,2-benzoxazole-5,6-dicarbonitriles. With a base, 4-(2-R-2-oxoethyl)-5-nitrophthalonitriles either undergo nitro-nitrite rearrangement resulting in 3-acyl-1,2-benzoxazole-5,6-dicarbonitriles or yield 2-R-benzofuran-5,6-dicarbonitriles with a nitro group displacement.

4,4'-Bipyridine and 2,7-diazapyrene derivatives (A) having two ammonioalkyl N-substituents were synthesized. The complex formation of these compounds with bis(18-crown-6)stilbene (D) was studied by spectrophotometry, cyclic voltammetry, (1)H NMR spectroscopy, and X-ray diffraction analysis. In MeCN, π-donor D and π-acceptors A form supramolecular 1:1 (D·A) and 2:1 (D·A·D) charge-transfer complexes. The D·A complexes have a pseudocyclic structure as a result of ditopic binding of the ammonium groups to the crown-ether fragments. The better the geometric matching between the components, the higher the stability of the D·A complexes (log K up to 9.39). A key driving force of the D·A·D complex formation is the excessive steric strain in the precursor D·A complexes. The pseudocyclic D·A complexes involving the ammoniopropyl derivative of 4,4'-bipyridine were obtained as single crystals. Crystallization of the related ammonioethyl derivative was accompanied by transition of the D·A complexes to a structure of the (D·A)(m) coordination polymer type.

Dibetaines of unsaturated viologen analogues that form supramolecular complexes with cucurbit[7]uril were synthesized. The pseudorotaxane structure and stability of the complexes were established by UV/Vis and 1 H NMR spectroscopy and by X-ray diffraction analysis. Complexes of this structure are prototypes of a light-controlled molecular machine.

Three styryl dyes of the 4-pyridine series that form syn-head-to-tail dimeric pairs in polycrystalline films were synthesised. NMR and UV/Vis spectroscopic studies showed that this promotes stereospecific [2+2]-autophotocycloaddition (PCA) in the dimeric pairs to give rctt-isomers of cyclobutane derivatives. For the dye with an N-ammoniopropyl substituent, this transformation was accomplished according to the single-crystal-to-single-crystal pattern. In aqueous solutions, the dyes and cucurbit[n]urils (CB[n], n = 7, 8) form complexes with a pseudorotaxane structure. CB[7] tends to form 1:1 complexes, and CB[8] forms 1:1 and 2:1 complexes. The structure of the termolecular complex formed by the betaine of the N-sulfonatopropyl styryl dye and CB[8] was determined by X-ray diffraction. The stability of the complexes was measured by 1 H NMR titration in a D 2 O/[D 3 ]MeCN (10:1) mixture (log K 1:1 ≥ 3.2, log K 2:1 ≥ 2.6). Free dyes and their complexes with CB[7] in water undergo only (E)/(Z) photoisomerisation. Termolecular complexes of all dyes with CB[8] were found to undergo effective stereospecific PCA reactions to give rctt isomers of cyclobutane derivatives. The 1:1 complexes of the obtained cyclobutanes with CB[8] (log K cb = 3.2-4.8) are less stable than those of the starting dyes with the same stoichiometry. Thus, CB[8] can play the role of a photocontrolled molecular assembler, i.e., even in the presence of 5 mol-% of CB[8], complete conversion of styryl dyes into the corresponding cyclobutane derivatives takes place upon irradiation in solution.

A novel peri -annulated heterocyclic system of 1,2-dihydrobenz[6,7]oxepino[4,3,2- cd ]indole was prepared starting from TNT via 4,6-dinitro-1-tosylindoline as a key intermediate. Base-induced C C bond shift in 1,2-dihydrobenz[6,7]oxepino[4,3,2- cd ]indoles affords isomeric 2,11-dihydrobenz[6,7]oxepino[4,3,2- cd ]indoles.

An improved method for the synthesis of formyl derivatives of N-methylbenzoazacrown ethers is proposed. They are prepared in up to 68% yields over fewer steps and with a much shorter time required for the last step. The stability constants of complexes formed by N-methylbenzoazacrown ethers and their structural analogs with alkali metal, alkaline-earth metal and ammonium cations were determined by 1H NMR titration in CD3CN. High stability of complexes of N-methyl derivatives of benzoazacrown ethers is demonstrated, comparable with or even exceeding the stability of benzocrown-ether complexes and markedly exceeding the stability of complexes of phenylazacrown ethers with the same macrocycle size. The structures of azacrown ethers and their complexes with Ba(ClO4)2 were studied by X-ray diffraction. A high degree of pre-organization of N-methylbenzoazacrown ethers toward the formation of complexes with metal and ammonium cations was noted, which is due to the clear-cut pyramidal geometry of the nitrogen atom and the orientation of the lone electron pairs (LEPs) of most heteroatoms towards the centre of the macroheterocycle. Copyright © 2009 John Wiley & Sons, Ltd.

2,4,6-Trinitrotoluene readily reacts with 1-nitroso-2-naphthol to afford 9,11-dinitrobenzo[f]naphtho[2,1-b][1,4]oxazepine. The nitro groups of the latter undergo displacement by O- and S-nucleophiles with preferential substitution of the 11-NO2 (peri-nitro group). The structures of the substitution products are confirmed by X-ray diffraction and 1H NMR NOE experiments.

Levoglucosenone (a chiral α,β-unsaturated ketone derivative of cellulose) serves as a starting compound in 2 and 3 step syntheses of chiral cyclopropanecarboxylic acids and 3-oxabicyclo[3.1.0]hexane-2-ones, respectively.

5,7-Dinitroquinazoline-4-ones undergo nucleophilic displacement of a nitro group with N-, S-, and O-nucleophiles. In contrast to previously studied dinitro-substituted benzoannulated five- and seven-membered heterocycles (where a high degree of selectivity was observed), these quinazolines mostly yield mixtures of regioisomeric substitution products. At the same time, primary and secondary amines react selectively to afford 5-aminoquinazolones (peri-substitution). A similar effect is observed for some other polynitroaromatic compounds with adjacent nitro and carbonyl groups. This phenomenon is attributed to a stabilization of the intermediate peri-sigma-complex by intramolecular hydrogen bond N(+)-H...O double bond C.

[Reaction: see text]. 1,3-dinitrodibenz[b,f][1,4]oxazepin-11(10H)-one, prepared by intramolecular displacement of nitro group in N-(2-hydroxyphenyl)-2,4,6-trinitrobenzamide, reacts with O- and S-nucleophiles to yield the products of mono- or bis-substitution of the nitro groups. The nitro group in position 3 is displaced first. This observation is in contrast with earlier results for the nitro-substituted benzoannulated five-membered heterocycles. This difference in reactivity is likely due to the increased steric hindrance for peri-nitro group displacement in the case of the benzoannulated seven-membered heterocycle. N-Alkylation of the nitro-substituted dibenz[b,f][1,4]oxazepin-11(10H)-ones yields analogues of a known antidepressant drug Sintamil. The structure of the products is confirmed by NOE experiments and alternative synthesis.

The enantiomers of asymmetric nitrogen compound 1 have been resolved; a chiral formal meso-form of diaziridine 2 has been obtained; a population of 1,2-cis-form 6a in solution has been found; and the crystal structures of 3–6 have been studied.

A series of promising benzoazacrown ethers with the nitrogen atom conjugated with the benzene ring were synthesized using a novel synthetic procedure based on stepwise transformation of the macroheterocycle. The structures and spectral properties of the resulting benzoazacrown ethers and their complexes with Ca2+ were studied by X-ray diffraction and 1H, 13C, and 15N NMR spectroscopy including the 2D NOESY technique. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione 1 is a new example of a compound capable of temperature-dependent racemate-conglomerate crystallization: at temperatures below 90°C crystals of the racemic compound (space group P1, Z=4) can be obtained, whereas above 100°C a conglomerate of (+)- and (−)-homochiral crystals (space group P212121, Z=4) forms and therefore it undergoes spontaneous resolution upon crystallization. Enantioselective analytical gas chromatography on a single crystal has been proposed as a simple method for detection of conglomerate formation. The 1H and 13C NMR spectra of 1 are analyzed in detail and the crystal structures of both species (racemic compound and single enantiomer) have been solved by X-ray structural analysis.

3,3'-(R)-Disubstituted 4,4'-azo-1,2,5-oxadiazole 2-oxides (furoxans) have been found to undergo a new rearrangement into 2-(furoxan-4-yl)-4-nitro-5-R-2H-1,2,3-triazole 1-oxides on heating in pertrifluoroacetic or peracetic acids.

Potentiostatic electrolysis (divided cell, anode compartment) of 1-methyl- and 1-phenylpyrroles in the presence of sodium 4-nitro-pyrazolate and sodium 3-nitropyrazolate in MeCN/MeOH gave the corresponding 2-(azol-1-yl)pyrroles in 20–43% current and substance yields.

The diazotization of anilines bearing the ortho-alkylazo group resulted in benzenediazonium salts 3, which exist in equilibrium with the 2-alkyl-1,2,3,4-benzotetrazinium salt cyclic isomers 4. The structures of 3 and 4 were confirmed by 1H, 13C, and 15N NMR studies. The relative proportions of the cyclic and open-chain forms were determined by a 1H NMR study. The 3 ⇄ 4 equilibrium is fast on the NMR timescale, and only one set of signals is observed in the 1H and 13C NMR spectra. The equilibrium strongly depends on the substituents on the aromatic ring, while being practically unaffected by the substituents (methyl or tert-butyl) on the azo group. Some of the investigated salts exist only in the cyclic form (4f, 4g), others only in the open-chain form (3k). (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

The synthesis of 1,2,3,4-benzotetrazine 1-oxides (BTOs) is described. Bromo-BTOs 4b−d were prepared by the intramolecular cyclization of diazonium salts bearing an ortho-(tert-butyl)-NNO-azoxy group. BTOs bearing electron-releasing substituents were obtained by nucleophilic displacements of bromine in 4b−d. The formation of the BTO cyclic system involves the intermediate 2-(tert-butyl)-1,2,3,4-benzotetrazinium 4-oxides, which arise from an N,N-[1,2]-shift of the tert-butyl group. Decomposition of BTOs involves opening of the tetrazine ring to afford ortho-azidonitroso derivatives, followed by their cyclization with the evolution of the N2 molecule to give benzofurazans. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Treatment of 5-nitro-pentan-2-one (1) with Me3SiOTf/Et3N leads to initial silylation of the C(O)Me-group to give regioisomeric silyl enol ethers 2a and 2b followed by double silylation of the NO2-group furnishing a mixture of N,N-bis(silyloxy)enamine 4a and enoxime TMS ether 6. Employment of a large excess of Me3SiOTf/Et3N triggers a cascade of eliminations and silylations to give a mixture of (E)-4-trimethylsilyloxy-2-trimethylsilyl-pent-2,4-dienenitrile (8) and 3-oxo-1-(1,1,1-trimethylsilyl)-1-cyclobutanecarbonitrile (9). The use of Me3SiCl/DBU changes the selectivity of silylation of 1 to give silyl nitronate 2c.

5-Nitro-4-phenylpentan-2-one (1) was found to undergo hitherto unknown Me3SiBr/Et3N-promoted cyclisation into the intermediate six-membered cyclic nitronate 5. Subsequent silylation of 5 led to the corresponding 2-trimethylsilyloxy-2H-[1,2]oxazine C, which undergoes a facile [4 + 2] cyclofragmentation to give 2-phenylpropenal oxime trimethylsilyl ether (6) in moderate yield. The intermediacy of the open-chain trimethylsilyl nitronate 2 and the cyclic nitronate 5 was confirmed by independent experiments. The transformation of the bicyclic nitronate 8 into the 8-trimethylsilyloxyimino-7-phenyloct-6-enoic acid trimethylsilyl ester (9) upon silylation proved the silylation/cycloreversion to be a key step in 1,3-azadiene moiety formation. The presented sequence of reactions could be carried out in one pot in low yield by a Me3SiOTf/Et3N-promoted hetero-[4 + 2] cycloaddition of 2-(trimethylsilyloxy)propene to (E)-2-nitro-1-phenyl-ethene, followed by silylation and fragmentation of the intermediate C.

The 1,3- and 1,4-bis(3-nitrofurazan-4-yl)benzenes have been synthesized by dehydration of 1,3- and 1,4-bis(2-aminoglyoximo- 1-yl)benzenes followed by oxidation of amino groups. The 1,3- and 1,4-bis(3-nitrofuroxan-4-yl)benzenes have been prepared by nitrozylation of tetrapotassium salts of 1,3- and 1,4-bis(2,2-dinitro-1-oximinoethyl)benzenes and thermally isomerized to 1,3- and 1,4-bis(4-nitrofuroxan-3-yl)benzenes.

The silylation of nitro compounds of general formula X 1 X 2 CHCH(Ar)CH 2 NO 2 with Me 3 SiBr Et 3 N at −30°C leads to hitherto unknown 2-( N , N -bis(trimethylsilyloxy)amino-2,3-dihydrofurans (X 1 =PhCO, X 2 =H) or to N , N -bis(trimethylsilyloxy)aminocyclopropanes (X 1 =X 2 =COOMe). N , N -Bis(trimethylsilyloxy)immonium cations appear to be the key intermediates in this process.

The reaction of primary amines bearing tertiary alkyl groups (e.g. R–NH2; R = tBu, 1-adamantyl) with nitrosobenzenes has been found to proceed by oxidative nucleophilic aromatic substitution of hydrogen, thereby affording N-(tert-alkyl)-ortho- and -para-nitrosoanilines. The replacement of hydrogen proceeds more rapidly than the replacement of ortho- or para-nitro or -bromo substituents. With p-nitronitrosobenzene, both ortho-hydrogen atoms are substituted to afford N,N′-di(tert-alkyl)-4-nitro-2-nitroso-1,3-phenylenediamines 8a,b. The addition of oxidizing agents (e.g. MnO2) increases the yield of products. 1H-, 13C-, 14N- and 15N-NMR studies have confirmed the structures of the compounds under investigation. In ortho-nitrosoanilines, the rotamer with the nitroso group syn to the amino group is favored.

We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl-3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds 12a and 14a displayed pronounced cytotoxicity in the NCI60 anticancer drug screen, with the ability to inhibit growth of multi-drug-resistant cancer cells.

Reaction of 2,4,6-trialkylglycolurils with epichlorohydrin under phase-transfer conditions affords the title compounds as diastereomeric mixtures.

The intramolecular reaction of the nitroso group with the azoxy side-chain in 2-( tert -butyl)-1-(2-nitrosophenyl)diazene 1- N -oxide provides the key step in a synthesis of the previously unknown 1-hydroxybenzo-1,2,3-triazole 3-oxide.

The action of the guanylyl-preferring RNase from Bacillus intermedius (binase) on a mixture of oligoadenylates with randomly distributed 2′-5′ and 3′-5′ internucleotide bonds [(A2′/3′p)n] under conditions sufficient for complete hydrolysis of poly(A) results in a mixture containing a single circular oligoadenylate and two series of linear oligoadenylates ending in cyclic 2′,3′-phosphate. Individual compounds formed upon digestion of (A2′/3′p)n with binase have been isolated. Their structure was determined on the basis of their chemical and enzymatic conversions and confirmed by 1H-, 13C- and 31P-NMR spectra. According to these data, the circular triadenylate contains one 2′-5′ and two 3′-5′ internucleotide bonds, linear oligoadenylates of one series contain exclusively 2′-5′ internucleotide bonds [(A2′p)nA>p], while each compound of the other series contains a single 3′-5′ internucleotide bond connecting the 5′-ultimate nucleotide residue with the penultimate one [A3′p(A2′p)n-1A>p]. The incubation of compounds of the former series A3′p(A2′p)n>p at pH 1.0 and the subsequent action of phosphatase results in successive formation of compounds of two other new series: A3′p(A2′p)nA2′(3′)p and A3′p(A2′p)nA.

A series of palladium(II) complexes with nitro- and formylbenzothiacrown-ether derivatives was synthesized. The spatial structure of the complexes was studied by NMR, X-ray diffraction analysis, and quantum chemical calculations (density functional theory). The cavity size and the ligand denticity were found to be crucial factors determining the geometric configuration of the thiacrown-ether complexes. Palladium(II) complexes with benzodithia-12(18)-crown-4(6) ethers were demonstrated to have a cis-configured S(2)PdY(2) fragment (Y = Cl, OAc). In the case of Pd(II) and benzodithia-21-crown-7 ethers, only complexes with a trans configuration of the S(2)PdY(2) fragment form. In the case of Pd(II) and nitrobenzomonothia-15-crown-5 ether, only 2(ligand):1(Pd) complex with trans configuration of the core fragment forms.

The first representatives of the 2-alkyl-1,2,5-oxadiazol-3(2H)-ones have been synthesized by the alkylation of trimethylsilyl derivatives of 3-hydroxyfurazans using triethyl orthoformate. The compounds obtained are investigated by 13C,14N,15N and 17O NMR, MS, IR and UV.

The first representatives of the 2-alkyl-1,2,5-oxadiazol-3(2H)-ones have been synthesized by the alkylation of trimethylsilyl derivatives of 3-hydroxyfurazans using triethyl orthoformate. The compounds obtained are investigated by 13C,14N,15N and 17O NMR, MS, IR and UV.

The reaction of primary amines bearing tertiary alkyl groups (e.g. R–NH2; R = tBu, 1-adamantyl) with nitrosobenzenes has been found to proceed by oxidative nucleophilic aromatic substitution of hydrogen, thereby affording N-(tert-alkyl)-ortho- and -para-nitrosoanilines. The replacement of hydrogen proceeds more rapidly than the replacement of ortho- or para-nitro or -bromo substituents. With p-nitronitrosobenzene, both ortho-hydrogen atoms are substituted to afford N,N′-di(tert-alkyl)-4-nitro-2-nitroso-1,3-phenylenediamines 8a,b. The addition of oxidizing agents (e.g. MnO2) increases the yield of products. 1H-, 13C-, 14N- and 15N-NMR studies have confirmed the structures of the compounds under investigation. In ortho-nitrosoanilines, the rotamer with the nitroso group syn to the amino group is favored.

Parent 3,7-diazabicyclo[3.3.0]octane-2,6-dione 5, the corresponding 1,5-dicarboxylic acid 4 and esters 3 have been synthesised for the first time; NMR spectra of the compounds were analysed, and the structures of 3b and 5 were studied by X-ray crystallography; hydrogen bonding generates self-assembly in the form of heterochiral infinite diagonal zigzag tape in the crystal of 5, while in the crystal structure of 3b the H-bonded layers consist of homochiral spirals and heterochiral chains.

The silylation of nitro compounds of general formula X 1 X 2 CHCH(Ar)CH 2 NO 2 with Me 3 SiBr Et 3 N at −30°C leads to hitherto unknown 2-( N , N -bis(trimethylsilyloxy)amino-2,3-dihydrofurans (X 1 =PhCO, X 2 =H) or to N , N -bis(trimethylsilyloxy)aminocyclopropanes (X 1 =X 2 =COOMe). N , N -Bis(trimethylsilyloxy)immonium cations appear to be the key intermediates in this process.

[reaction: see text] The novel heterocyclic system 10 with the phenanthrene type skeleton, in which the benzene ring is annulated with two 1,2,3,4-tetrazine 1,3-di-N-oxide rings, is of considerable interest in the context of the high nitrogen system stability and from a heteroaromaticity standpoint. The step-by-step synthetic approach to this system involves treatment of 5 with N2O5, resulting in the first 1,2,3,4-tetrazine 1,3-dioxide ring formation. The following displacement of the chlorine atom at the 6-position with ammonia and subsequent repeated treatment with N2O5 results in the second 1,2,3,4-tetrazine 1,3-dioxide ring formation. The structure of 10 was confirmed by a 13C and 14N NMR study.

The synthetic approaches to novel N- and SO2-containing bi-, tri- and tetracyclic systems, 6,8-di- and 2,4,6,8-tetraalkyl-7-oxo-3-thia-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,3-dioxides, 8,12-dioxo-9,11-dimethyl-4-thia-1,3,5,7,9,11-hexaazatricyclo[5.5.1.010,13]-tridecane-4,4-dioxide and 8,16-dioxo-3,5,11,13-tetramethyl-4,12-dithia-1,3,5,7,9,11,13,15-octaazatetracyclo[7.7.2.07,17.015,18]octa-decane-4,4,12,12-tetraoxide, have been developed.