Synthesis and properties of a new fused heterocyclic system 12<Emphasis Type="Italic">H</Emphasis>-benzo[5,6][1,2,4]triazepino[3,4-<Emphasis Type="Italic">a</Emphasis>]isoindol-5(6<Emphasis Type="Italic">H</Emphasis>)-one

12H-Benzo[5,6][1,2,4]triazepino[3,4-a]isoindol-5(6H)-one was synthesized by the condensation of anthranilic acid hydrazide with o-phthalaldehyde. The structure of this compound was established by the X-ray diffraction study of its isopropyl derivative. The mechanism of formation of this compound was suggested and its alkylation reactions were investigated. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 180–185, January, 2008.     

Synthesis and NMR spectroscopy investigations of functionalized 8,8,10-trimethyl-4-phenyl-7,8-dihydro-2<Emphasis Type="Italic">H</Emphasis>,6<Emphasis Type="Italic">H</Emphasis>-pyrano[3,2-<Emphasis Type="Italic">g</Emphasis>]chromene-2,6-diones and their spirothiadiazole derivatives

New functionalized derivatives of 8,8,10-trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]-chromene-2,6-dione – analogues of the natural compound graveolone – possessing hydrazine, hydroxylamine, and thiosemicarbazide residues were synthesized and their reactions with acetic anhydride were studied. The structure of the obtained compounds was confirmed by NMR spectroscopy. Correspondence: Viktoria Moskvina, Chemistry Department, Kyiv National Taras Shevchenko University, 60, ul. Vladimirskaya, 01033 Kyiv, Ukraine.     

Synthesis of 2,3-<Emphasis Type="Italic">cis</Emphasis> Stereomeric Emetamines <Emphasis Type="Italic">via Reissert</Emphasis> Compounds

Summary. Alkylation of Reissert compounds with certain benzoquinolizinone derivatives followed by hydrolytic cleavage afforded the core of the title compounds in a two step sequence. Finally, the lactam intermediates were reduced with DIBAH giving the target compounds, the structural and stereochemical assignments of which were achieved by ¹³C NMR spectroscopy. Part of PhD thesis, LMU München, D     

An Improved Stereocontrolled Route to <Emphasis Type="Italic">cis</Emphasis>-Erythrinanes by Combined Intramolecular <Emphasis Type="Italic">Strecker</Emphasis> and <Emphasis Type="Italic">Bruylants</Emphasis> Reaction

Summary. Condensation of (2-iodophenyl)ethylamines with cyclohexanoylacetaldehyde provided the corresponding aldimines which were reduced yielding secondary phenethylcyclohexanoylethylamines. These in turn were appropriate intermediates to prepare several erythrinanes by a sequential intramolecular Strecker and intramolecular Bruylants reaction. In contrast, the C-ring homologue schelhammeranes were not available on this route.Part of PhD thesis, LMU München, D     

One step synthesis of 14-alkyl- or aryl-14<Emphasis Type="Italic">H</Emphasis>-dibenzo[<Emphasis Type="Italic">a</Emphasis>,<Emphasis Type="Italic">j</Emphasis>]xanthenes using sodium hydrogen sulfate as catalyst

A simple and environmentally benign procedure for the synthesis of 14-alkyl- or aryl-14H-dibenzo[a,j]xanthenes is described through a one-pot condensation of 2-naphthol with aryl or alkyl aldehydes in the presence of sodium hydrogen sulfate as a catalyst under solvent-free conditions. Correspondence: Mohammed M. Hashemi, Department of Chemistry, Sharif University of Technology, P.O. Box 11365-9516, Tehran, Iran.     

Rapid molecular typing of <Emphasis Type="Italic">Tuber melanosporum</Emphasis>, <Emphasis Type="Italic">T. brumale</Emphasis> and <Emphasis Type="Italic">T. indicum</Emphasis> from tree seedlings and canned truffles

We have developed new DNA extraction and purification procedures for investigation of mycorrhized seedlings and canned truffles. Use of these procedures on approximately 100 mg initial material enabled good sample representation. For mycorrhized seedlings, Taq polymerase inhibitors were discarded irrespective of tree species. In routine analysis we systematically used consensus primers ITS1/ITS4 to check the absence of Taq polymerase inhibitors and the presence of fungus DNA. Positive response with ITS validates other positive or negative PCR results. Absence of amplification with ITS prevents validation of other results. For canned truffles, DNA harvested from ascocarps sterilized for one and a half hours at 115°C was amplified with specific primers. We have developed consensus primers, named R12/F12, to check for the presence of amplifiable fungus DNA and the absence of Taq polymerase inhibitors. Here also, positive response with consensus R12/F12 validates other positive or negative PCR results. We have developed one primer pair specific for T. brumale and another specific for T. melanosporum. We can then characterize these two taxa, which enables the use of truffle or truffled French designations. We can also characterize T. indicum, the Asiatic black truffle that might fraudulently be sold as T. melanosporum and T. brumale. These three specific primer pairs were used independently of DNA extraction from tree seedlings or canned truffles. Our process is specific, sensitive, convenient, and quick.J.P. Douet and D. Mabru have contributed equally to this work     

Synthesis of 4<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carbaldoxime 3-oxides and 4<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carbonitrile 3-oxides

The condensation of 3-hydroxyamino-3-methylbutan-2-one or 3-ethyl-3-hydroxyamino-pentan-2-one with aldehydes and ammonia afforded a series of new 1-hydroxy-4-methyl-2,5-dihydroimidazoles, whose oxidation gave rise to the corresponding 5-methyl-4H-imidazole 3-oxides. The latter, like 1-hydroxy-4-methyl-2,5-dihydroimidazoles, react with PrⁱONO in the presence of bases to form 4H-imidazole-5-carbaldoxime 3-oxides, which are transformed into 4H-imidazole-5-carbonitrile 3-oxides in the reaction with TsCl in the presence of Et₃N. The by-products produced in different steps of the synthesis were isolated and characterized. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1487–1503, July, 2008.     

Screening and Immobilization <Emphasis Type="Italic">Burkholderia</Emphasis> sp. GXU56 Lipase for Enantioselective Resolution of (<Emphasis Type="Italic">R</Emphasis>,<Emphasis Type="Italic">S</Emphasis>)-Methyl Mandelate

Microorganisms producing lipase were isolated from soil and sewage samples and screened for enantioselective resolution of (R,S)-methyl mandelate to (R)-mandelic acid. A strain designated as GXU56 was obtained and identified as Burkholderia sp. Preparing immobilized GXU56 lipase by simple adsorption on octyl sepharose CL-4B, the optimum temperature was shifted from 40 °C (free lipase) to 50 °C (immobilized lipase), and the optimum pH was shifted from 8.0 (free lipase) to 7.2 (immobilized lipase). The immobilized enzyme displayed excellent stability in the pH range of 5.0–8.0, at the temperatures below 50 °C and in organic solvents compared with free enzyme. Enantioselectivity ratio for (R)-mandelic acid (E) was dramatically improved from 29.2 to more than 300 by applying immobilized lipase in the resolution of (R,S)-methyl mandelate. After five cycles of use of immobilized lipase, conversion and enantiomeric excess of (R)-mandelic acid were 34.5% and 98.5%, respectively, with enantioselectivity ratio for (R)-mandelic acid (E) of 230. Thus, octyl-sepharose-immobilized GXU56 lipase can be used as a bio-resolution reagent for producing (R)-mandelic acid.     

Synthesis of pyrano[2,3-<Emphasis Type="Italic">f</Emphasis>]chromen-2,8-diones and pyrano[3,2-<Emphasis Type="Italic">g</Emphasis>]chromen-2,8-diones based on <Emphasis Type="Italic">o</Emphasis>-hydroxyformyl(acyl)neoflavonoids

Novel pyrano[2,3-f]chromen-2,8-diones and pyrano[3,2-g]chromen-2,8-diones were prepared based on modified analogs of natural o-hydroxyformyl(acyl)neoflavonoids. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 15–20, January–February, 2008.     

Determination of epoxides by high-performance liquid chromatography following derivatization with <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diethyldithiocarbamate

A reversed-phase, high-performance liquid chromatography (RP-HPLC) method that allows quantitation of low levels of epoxides has been described. The method involved derivatization of epoxides using 100- to 1,000-fold excess N,N-diethyldithiocarbamate (DTC) at 60 °C for 20 min at neutral pH. The unreacted DTC was then decomposed to CS₂ and diethyl amine by acidification of the reaction mixture to pH 2 using orthophosphoric acid. The first two steps could be performed in the same reaction vessel by sequential addition of reagents. In the final step, an aliquot (20 μL) of the derivatized sample was analyzed for the presence of stable esters of DTC by RP-HPLC using a Supelcosil LC-18-S (150 × 4.6-mm) column and a mobile phase consisting of 40% (v/v) acetonitrile in water at a flow of 1 mL min⁻¹. Using UV detection at 278 nm, the epoxides gave linear responses in the concentration range of 0.25 to 50 μM. The method is robust, and as low as 5 pmol of the analyte could be successfully detected and quantified with recoveries of ≥94%. Following a minimal pretreatment such as ultrafiltration (molecular weight cutoff 5,000 Da), the method is suitable for analysis of epoxides in complex physiological fluids (e.g., fetal bovine serum). The method has been rigorously evaluated and adapted in our laboratory for routine analysis and determination of stability of epoxides of 1,3-butadiene and other alkenes added to cell cultures.     

Synthesis and pharmacological activity of some synthesized polyazacyclopenta[<Emphasis Type="Italic">a</Emphasis>]naphthalenes and pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridines using 2-amino-6-methyl-4-phenylnicotinonitrile as synthon

Abstract  A series of pyridines, pyrimidines, and their derivatives were synthesized using 2-amino-6-methyl-4-phenylnicotinonitrile as starting material. Thirteen new heterocyclics containing a pyridine ring were thus prepared. Pharmacological screening showed that many of these compounds have good anti-inflammatory and analgesic activity comparable with those of diclofenac potassium and valdecoxib as reference drugs. Assignment of the structures of the new compounds was based on chemical and spectroscopic evidence. Synthesis, spectroscopic data, and pharmacological properties of the compounds are reported in detail. Graphical Abstract        

Syntheses of (<Emphasis Type="Italic">E</Emphasis>)- and (<Emphasis Type="Italic">Z</Emphasis>)-3-styrylchromones

Several (E)- and (Z)-3-styrylchromones were prepared by two different methodologies, the Wittig reaction of chromone-3-carboxaldehyde with benzylic ylides and the Knoevenagel condensation of chromone-3-carboxaldehyde with phenylacetic acids in the presence of potassium tert-butoxide under microwave irradiation. The Knoevenagel reaction followed by a decarboxylation offered an efficient and diastereoselective method for preparing (E)-3-styrylchromones in a shorter reaction time. It was also demonstrated that phenylacetic acid can also be substituted with success by phenylmalonic acid. The stereochemistry of all products was assigned by NMR experiments. Correspondence: Artur M. S. Silva, Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal.     

Synthesis of imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridones and imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]acridines as potential antibacterial agents

Abstract  New imidazo[4,5-a]acridone derivatives were synthesized from the rearrangement of 3H-imidazo[4′,5′:3,4]benzo[c]isoxazoles. New imidazo[4,5-a]acridines were obtained from the reaction of imidazo[4,5-a]acridones in boiling POCl₃. All of these compounds exhibited antimicrobial activities comparable to streptomycin as reference drug. Graphical abstract        

The smallest Hosoya index in (<Emphasis Type="Italic">n</Emphasis>, <Emphasis Type="Italic">n</Emphasis> + 1)-graphs

A (n, n + 1)-graph G is a connected simple graph with n vertices and n + 1 edges. In this paper, we determine the lower bound for the Hosoya index in (n, n + 1)-graphs in terms of the order n, and characterize the (n, n + 1)-graph with the smallest Hosoya index.     

Antioxidant flavonoids from <Emphasis Type="Italic">Tamus communis</Emphasis> ssp. <Emphasis Type="Italic">cretica</Emphasis>

A new flavonoid, kaempferol-3,4′-di-O-α-L-rhamnopyranoside (1), and three known flavonoids (2–4) were isolated from the aerial parts of T. communis L. The structure of the new compound was elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed significant antioxidant activity (IC₅₀ 187.151 ± 0.821 μM, and 92.079±0.513 μM, respectively), whereas compounds 3 and 4 showed moderate activity in DPPH free radical scavenging assays. Published in Khimiya Prirodnykh Soedinenii, No. 3, pp. 295–297, May–June, 2009.     

Crystal and molecular structure of new tetrahydrobenzo[<Emphasis Type="Italic">e</Emphasis>]pyrano[4,3-<Emphasis Type="Italic">b</Emphasis>]pyridines

Three tetrahydrobenzo[e]pyrano[4,3-b]pyridines formed in a diethyl 2,4,6-trioxoheptanedicarboxylic ether-substituted salicylic aldehyde-ammonium acetate system were studied by single crystal X-ray diffraction. After the introduction of a methoxy group in the tricyclic system, the tetrahydropyridine and pyrane rings adopted the half-chair conformation, while in the unsubstituted compound, the tetrahydropyridine ring has a distorted boat conformation, and the pyrane ring has a C-envelope conformation. In the compounds, the N-H?O and O-H?O intermolecular hydrogen bonds give rise to the development of chain structures. In two of the three compounds examined, the hydrogen atoms at the chiral centers are in the trans-position, as in the structure of natural tetrahydrocannabinols.     

8-Methoxy-5-methyl-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-cyclopenta[<Emphasis Type="Italic">a</Emphasis>]naphthalene: synthesis and reactivity

A new single-step approach to cyclopenta[a]naphthalenes through TiCl₄-catalyzed reactions of 1-trimethylsilyloxycyclopentene with arylacetaldehydes was proposed. 8-Methoxy-5-methyl-2,3-dihydro-1H-cyclopenta[a]naphthalene and its derivatives were studied in oxidation and bromination reactions, as well as in hydrolytic cleavage of the O-Me bond.     

An efficient <Emphasis Type="Italic">Mannich</Emphasis>-type synthesis of <Emphasis Type="Italic">bis</Emphasis>(pyrido[2,1-<Emphasis Type="Italic">b</Emphasis>][1,3,5]thiadiazin-7-yl)-methanes

Morpholinium 3-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-thiolate upon treatment with primary amines and a formaldehyde excess under mild conditions produces bis(pyrido[2,1-b][1,3,5]thiadiazin-7-yl)methane derivatives in good yields (67–87%). Correspondence: Victor V. Dotsenko, State Enterprise “Luganskstandartmetrology”, 91021 Lugansk, Ukraine.     

Recyclization of 1,3-dialkyl-6-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,5(3<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>)-diones into imidazole derivatives

Treatment of 5-amino-1,3-dialkyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones with sodium nitrite in aqueous HCl gave 1,3-dialkyl-1H-imidazo[4,5-b]pyridine-2,5(3H,4H)-diones which were nitrated with potassium nitrate in sulfuric acid to 6-nitro derivatives, and the latter underwent recyclization into 4-amino-1,3-dialkyl-5-(1H-pyrazol-5-yl)-2,3-dihydro-1H-imidazol-2-ones by the action of hydrazine hydrate.