JSCS - Vol 63, No2

J. Serb. Chem. Soc. 63(2)93-112(1998)
UDC 547.82/.821
JSCS-2511
Original scientific paper

The synthesis, pharmacological evaluation and conformational analysis of (±) cis- and (±) trans-3-carbomethoxy fentanyl - "iso-carfentanil"

I. V. MICOVIC, M. D. IVANOVIC*, S. VUCKOVIC**, D. JOVANOVIC-MICIC,** D. BELESLIN**, Lj. DOSEN-MICOVIC and V. D. KIRICOJEVIC*

Faculty of Chemistry, University of Belgrade, Studentski Trg 16,
P.O. Box 158, YU-11001, Belgrade,
*Institute of Chemistry, Technology and Metallurgy, Center for Chemistry, Njegoseva 12, P.O.Box 815, Belgrade and
**Department of Pharmacology, Toxicology and Clinical Pharmacology, Medical Faculty, P.O. Box 662,
Dr Subotica 1, Belgrade, Yugoslavia

(Received 25 July 1997)
A novel analogue of fentanyl, 3-carbomethoxyfentanyl, or "iso-carfentanil", was synthesized by a simple and efficient route. In the first step phenethylamine was condensed with two equivalents of methyl acrylate to afford the amino-diester 1b in quantitative yield. Dieckmann cyclization of this intermediate yielded 3-carbomethoxy N-phenethyl-4-piperidone 2 in ca. 80% yield, after mild hydrolysis. Condensation of this b-keto ester with aniline in acetic acid gave the stable enamine 3 (70% yield) which was then reduced with NaBH₃CN in methanol at pH ~ 5, to yield 4-anilino-3-carbomethoxy-N-phenethyl piperidine, quantitatively. This intermediate was obtained as a 50:50 mixture of the (±) cis and (±) trans isomers, 4a and 4b, respectively. After the mixture of diastereoisomers was separated on a neutral aluminium oxide column, the pure 4a and 4b isomers were acylated with propionyl chloride, thus completing the synthesis of 3-carbomethoxy fentanyl 5a and 5b. The relative stereochemistry was determined by ¹H-NMR spectroscopy. These compounds present regioisomers of carfentanil, one of the most potent narcotic analgesic known to date. Preliminary pharmacological evaluation (tail-withdrawal test in rats) revealed substantially reduced potency of both diastereoisomers, the (±) trans 5b in particular, compared to carfentanil. The computational (molecular mechanics) search of the low energy regions of the conformational space of the cis 5a and trans 5b isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible, the trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl.

Key words: 3-carbometoxyfentanyl, synthesis, pharmacological evaluation, conformational analysis.

J. Serb. Chem. Soc. 63(2)113-116(1998)
UDC 577.17/.171.3:542.9
JSCS-2512
Original scientific paper

Synthesis and biological activity of two new D-secoestrone derivatives

JULIJANA A. PETROVIC, TATJANA Z. STEPIC, VJERA M. PEJANOVIC*, LJUBICA D. MEDIC MIJACEVIC*, RADMILA Z. KOVACEVIC, SILVANA A. ANDRIC and SLOBODANKA M. STANKOVIC

Faculty of Science, University of Novi Sad, Trg Dositeja Obradovica 3, YU-21000 Novi Sad, and
*ICN Yugoslavia, Institute, 29. Novembra 111, YU-11000 Belgrade, Yugoslavia

(Received 24 July 1997)
Addition of phenyl lithium to 3-methoxyestra-1,3,5(10)-trien-16,17-dione 16-oxime (1) afforded the corresponding 17a-phenyl-17b-hydroxy derivative 2, which, under Beckmann fragmentation reaction conditions, gave the 16,17-seco derivative 3. Sodium borohydride reduction of the primary fragmentation product resulted in formation of a sole product 4, which, according to X-ray structural analysis, represents the 17(S)-isomer. In biological tests both compounds 3 and 4 showed practically a complete loss of estrogenic activity.

Key words: Seco-estrone derivatives, synthesis and biological action of, Beckmann fragmentation reaction.

J. Serb. Chem. Soc. 63(2)117-123(1998)
UDC 547.771.2:542.9
JSCS-2513
Original scientific paper

Synthesis and antibacterial activity of some novel p-(N-benzoyl)aminobenzoic acid derivatives

H. M. HASSAN

Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt

(Received 17 July 1997)
Reaction of p-(N-benzoyl)aminobenzoic acid (I) with PCl₅ furnished the acid chloride (II) which was reacted with amines, hydrazine and hydroxy compounds to give the corresponding amide (III-IX), hydrazide (X) and ester (XI-XV) derivatives, respectively. 1-[p-(N-Benzoyl)aminobenzoyl]-3-methyl-4-substituted-phenyl-6-imino-4,7-dihydro-1,3-thiazino[5,4-d]pyrazolones (XXIII-XXV) have been synthesized by the condensation of 1-[p-(N-benzoyl)aminobenzoyl]-4-arylideno-3-methyl-5-pyrazolones (XX-XXII) with thiourea in methanolic KOH.

Key words: p-(N-benzoyl)aminobenzoic acid, derivative of, pyrazolones, synthesis, antibacterial activity.

J. Serb. Chem. Soc. 63(2)125-130(1998)
UDC 547.654.4/.657
JSCS-2514
Original scientific paper

Synthesis and antimicrobial activity of some new Mannich bases, N-(2-hydroxy-1-naphthyl)amino acid, methyl ester and hydrazide derivatives

H. M. HASSAN and S. A. M. SHEDID

Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt

(Received 10 September 1997)
The synthesis of a series of Mannich bases, N-(2-hydroxy-1-naphthyl)amino acids (I-VIII), methyl esters (IX-XVI) and the corresponding hydrazides (XVII-XXIII) was achieved. The derivatives containing the residues of L-Ala, L-Phe and L-Tyr were found to be active against a number of microorganisms.

Key words: Mannich bases, N-(2-hydroxy-1-naphthyl)amino acids, antimicrobial activity.

J. Serb. Chem. Soc. 63(2)131-135(1998)
UDC 547.913.2/.7:581.135.5
JSCS-2515
Original scientific paper

Sesquiterpene lactones from plant species Centaurea solstitialis L.

VELE TESEVIC, VLATKA VAJS*, NINA TODOROVIC*, DEJAN DJOKOVIC,
PETAR MARIN** and SLOBODAN MILOSAVLJEVIC

Faculty of Chemistry, Studentski trg 16, P.O.Box 158, YU-11001 Belgrade,
*Institute for Chemistry, Technology and Metallurgy, Njegoseva 12, YU-11000 Belgrade and
**Faculty of Biology, Studentski trg 16, YU-11001 Belgrade, Yugoslavia

(Received 30 September 1997)
The identification of nine known guaianolides, i.e., solstitialin A, its 13-acetate, linichlorin B, cynaropicrin, centaurepensin (chlorohyssopifolin A), 17-epi-centaurepensin, 19-desoxychlorojanerin, 11b,13-dihydrodesacylcynaropicrin and 8-desacylcentau-repensin-8-O-(4-hydroxy)tiglate in the aerial parts of Centaurea solstitialis is reported. The last four lactones were isolated for the first time from this species. Other compounds detected in this extract, not found before in C. solstitialis, were syringaresinol (lirioresinol B) and arctigenin (the known lignans).

Key words: Centaurea solstitialis, guaianolides, solstitialin, linichlorin, cynaropicrin, centaurepensin, 19-desoxychlorojanerin, 11b,13-dihydrodesacylcynaropicrin, 8-desa-cylcentaurepensin-8-O-(4-hydroxy)tiglate, syringaresinol, arctigenin.

J. Serb. Chem. Soc. 63(2)137-142(1998)
UDC 647.458:547.455.627
JSCS-2516
Original scientific paper

On the mannogalactan from the fruit bodies of Pleurotus ostreatus (Fr.) Quel

DRAGICA JAKOVLJEVIC, JELENA MILJKOVIC-STOJANOVIC*, MILANKA RADULOVIC and MIRJANA HRANISAVLJEVIC-JAKOVLJEVIC*

Institute of Chemistry, Technology and Metallurgy, Belgrade and
*Faculty of Chemistry, University of Belgrade, P.O. Box 158, YU-11001 Belgrade, Yugoslavia

(Received 16 July 1997)
The heteropolysaccharide composed of D-mannose, D-galactose and 3-O-met-hyl-D-galactose was isolated by trichloroacetic acid extraction of the fruit bodies of Pleurotus ostreatus fungi. On the basis of chemical and physical methods common in structural analysis of polysaccharides, the main structural feature of this heteropolysaccharide was found to be a backbone chain made up of (1 -> 6)-linked a-D-galactopyranoses and 3-O-Me-a-D-galactopyranoses, a part of both these units being substituted in the position O-2 with b-D-mannopyranose residues.

Key words: Pleurotus ostreatus, mannogalactan, structure.

J. Serb. Chem. Soc. 63(2)143-147(1998)
UDC 547.593.21/.211:547.412.12
JSCS-2517
Original scientific paper

Relative reactivities of cycloalkanols toward trichloromethyl radical

JOVAN N. MILOVANOVIC and MILAN JOKSOVIC

Departtment of Chemistry, Faculty of Science, University of Kragujevac, Kragujevac, P.O.Box 60, YU-34000 Kragujevac, Yugoslavia

(Received 11 March 1997)
The relative reaction rates of cycloalkanols with common and medium rings towards the trichloromethyl radical were investigated and a divergence from the usual order of reactivity was observed for cyclopentanol, cyclohexanol, as well as cis- and trans-4-t-butylcyclohexanol. It is proposed that, under specific circumstances, the reactivity of the carbon-hydrogen bond in the cyclic system is controled not by I-strain or the incipient radical stability, but by hyperconjugation of neighbouring carbon-hydrogen bonds with the reaction site in the transition state.

Key words: relative reactivities, cycloalkanols, trichloromethyl radicals.

J. Serb. Chem. Soc. 63(2)149-157(1998)
UDC 661.879.1/661.8.717 733/:543.422
JSCS-2518
Original scientific paper

Infrared spectra of uranyl compounds in alkali halide matrices:oxalates and acetates

SLOBODAN V. RIBNIKAR and MILAN S. TRTICA*

Faculty of Physical Chemistry, University of Belgrade, P.O. Box 137, YU-11001 Belgrade, and
*The Vinca Institute of Nuclear Sciences, Laboratory of Physical Chemistry, P.O.Box 522,
YU-11001 Belgrade, Yugoslavia

(Received 16 July 1997)
The infrared absorption spectra of uranyl oxalate and acetate in KBr matrices in the 4000-250 cm^-1 range have been examined. Special attention was devoted to the dependence of the IR spetra on the sample treatment temperature and to the shape of the n₃ bands appearing in the range of carbon dioxide laser radiation. Heat treatment up to some 270°C leads to a narrowing of the band. Higher temperatures decompose the anions to carbon dioxide, while the uranyl ions are converted either to UO₂ or potassium diuranate.
Key words: infrared spectroscopy, uranyl compounds.

J. Serb. Chem. Soc. 63(2)159-164(1998)
UDC 66.061.34-084(001.5)
JSCS-2519
Review paper

REVIEW
Stage additivity method and its application to the calculation of counter-current extractors with backmixing

ALEKSANDAR S. TOLIC

Faculty of Metallurgy and Technology, University of Montenegro YU-81000 Podgorica, Yugoslavia

(Received 30 October 1997)
1. Introduction
2. Stage additivity method
3. Analytical procedure for the linear case of equilibrium distribution of an independent solute
4. Numerical procedure for the general case of equilibrium distribution of an independent solute
5. Graphical procedure for the general case of equilibrium distribution of an independent solute
6. Application of the stage additivity method for the general case of equilibrium distribuiton of two interdependent solutes

Key words: stagewise model, backmixing, axial dispersion, mass transfer, extractor, calculation.

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