Regular Issue

Vol. 48, No. 6, 1998

19 data found. 1 - 19 listed
Communication | Regular issue | Vol 48, No. 6, 1998, pp. 1103 - 1106
Published online:
DOI: 10.3987/COM-98-8135
Facile in situ Preparation of o-Azaxylylene from N,O-Diethoxycarbonyl-o-aminobenzyl Alcohol

Kota Nishiyama, Hajime Kubo,* Tomohide Sato, Kimio Higashiyama, and Shigeru Ohmiya

*Department of Synthetic Organic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan


o-Azaxylylenes were generated only by gentle refluxing of N,O-diethoxycarbonyl-o-aminobenzyl alcohols in o-dichlorobenzene and then underwent the Diels-Alder reaction with dienophiles to give 1,2,3,4-tetrahydroquinolines.

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Communication | Regular issue | Vol 48, No. 6, 1998, pp. 1107 - 1110
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DOI: 10.3987/COM-98-8137
Merckonine, a New Aconitine-Type Norditerpenoid Alkaloid with a -N=C-19H Functionality

Haridutt K. Desai, L. Phillip Silverman, and S. William Pelletier*

*Institute for Natural Products Research and Department of Chemistry, Chemistry Building, The University of Georgia, Chemistry Building, AthensGeorgia 30602-2556, U.S.A.


From a commercial source of aconitine, "Aconitine Potent Merck", isolated from Aconitum napellus L., Lot No. 30169, a new minor norditerpenoid alkaloid, "merckonine" has been isolated. Structure (1) for the new alkaloid was assigned on the basis of its physical and spectroscopic data and synthesis from aconitine. The known alkaloids 3-deoxyaconitine, aconitine and mesaconitine were also isolated in pure form from this commercial source.

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Communication | Regular issue | Vol 48, No. 6, 1998, pp. 1111 - 1116
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DOI: 10.3987/COM-98-8143
Regioselective Nucleophilic Substitution of Halogen Derivatives of 1-Substituted 4-Oxo-1,4-dihydroquinoline-3-carboxylic Acids

István Hermecz,* Lelle Vasvári-Debreczy, Benjamin Podányi, Géza Kereszturi, Mária Balogh, Ágnes Horváth, and Péter Várkonyi

*CHINOIN Pharmaceutical and Chemical Works Ltd., P. O. Box 110, H-1325 Budapest, Hungary


The rate of the nucleophilic displacement of the fluoro atom of 7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate could be enhanced either by the introduction of further fluoro atom(s) into position(s) 6 and/or 8, or by the formation of a boron chelate (e.g. 3). The regioselectivity of the nucleophilic substitution of the chloro atom in 1-substituted 6-fluoro-7-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids could also be enhanced by the formation of a boron chelate (e.g. 7).

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Communication | Regular issue | Vol 48, No. 6, 1998, pp. 1117 - 1120
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DOI: 10.3987/COM-98-8156
Syntheses of 1-Hydroxytryptamines and Serotonins Having Fattyacyl or (E)-3-Phenylpropenoyl Derivatives as an Nb-Substituent, and a Novel Homologation on the 3-Substituent of the 1-Hydroxytryptamines upon Treatment with Diazomethane

Masanori Somei,* Harunobu Morikawa, Koji Yamada, and Fumio Yamada

*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan


1-Hydorxytryptamines (6a-f) having (E)-3-phenyl-, (E)-3-(4-hydroxyphenyl)-, (E)-3-(4-hydroxy-3-methoxyphenyl)propenoyl, octanoyl, hexadecanoyl, and docosanoyl group as a Nb-substituent are prepared for the first time. Preparations of serotonins (2a-c, e) from the corresponding 1-hydroxytryptamines (6a-c, e) are also reported. A novel homologation on the 3-substituent of 1-hydroxytryptamines is discovered upon treatment with diazomethane in chloroform or dichloromethane.

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1121 - 1138
Published online:
DOI: 10.3987/COM-97-7898
Synthesis of 2-Alkylidene-3,3-dialkyl-1,4-dithianes and Their Oxathiane Analogues by 1,2-Sulphur Migration

M. Teresa Barros, Christopher D. Maycock,* and Lúcia S. Santos

*Instituto de Tecnologia Quimica e Biologia, Universidade Nova de Lisboa, Rua da Quinta Grande 6, 2780 Oeiras, Portugal


2-Alkylidene-3,3-dialkyl-1,4-dithianes and their oxathiane analogues were prepared from 1,2-diketones by a process involving formation of the monodithioacetal, transformation to a tertiary alcohol with organometallic reagents and ultimately 1,2-sulphur migration using methanesulphonyl chloride in pyridine as the activating agent.

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1139 - 1149
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DOI: 10.3987/COM-97-8087
Synthesis of 5-Substituted Indole Derivatives, I. An Improved Method for the Synthesis of Sumatriptan

Béla Pete, István Bitter, Csaba Szántay, Jr., István Schön, and László Töke*

*Department of Organic Chemical Technology, Technical University Budapest, H-1521 Budapest, Gellért tér 4, Hungary


An improved synthesis of sumatriptan (1b) via Fischer cyclization was achieved by introducing the ethoxycarbonyl group on the N-atom of the sulphonamide moiety in N-methyl-4-hydrazinobenzenemethanesulphonamide (7). As a result, substitution on the benzylic carbon of the indole nucleus could be avoided; however, formation of 1,1-bis-(indol-2-yl)-4-dimethylaminobutane-type by-product (19) was observed. The indolization procedure was optimized to suppress the unwanted side reaction. The N-protection of the sulphonamide moiety was found to be beneficial regarding the purification of the 3-[2-(dimethylamino)ethyl]-N-ethoxycarbonyl-N-methyl-1H-indole-5-methanesulphonamide (18).

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1151 - 1156
Published online:
DOI: 10.3987/COM-98-8103
Electrochemistry of 7-Carboethoxycycloheptatriene and Its Aza-analogues: Ring Contruction of Azepine Derivatives to AnilineDerivatives by Oxidation and N—N Bond Rupture of Diazepine Derivatives to 1-Amino-4-cyano-1,3-butadiene Derivatives by Reduction

Satoru Kondo, Hiroshi Suzuki, Tatsuya Hattori, Takayasu Ido, and Katsuhiro Saito*

*Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan


Electrochemical reduction or oxidation of 7-ethoxycarbonylcycloheptariene afforded 2-ethoxycarbonylcycloheptatriene and ethyl phenylacetate, respectively. N-Alkoxycarbonyl-1H-azepine formed N-alkoxycabonylaniline in electrochemcial oxidation via a ring contruction. N-Alkoxycarbonyl-1H-1,2-diazepine afforded N-alkoxycarbonyl-1-amino-4-cyano-1,3-butadiene in electrochemical reduction via an N-N bond fission.

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1157 - 1167
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DOI: 10.3987/COM-98-8117
Synthesis of Thieno[2,3-d]pyrimidines and Aminopyrimidines from 2-Alkoxy-5-cyano-4-thioxopyrimidine Intermediates

Matthias Rehwald* and Karl Gewald

*Department of Organic Chemistry, Technical University of Dresden, Mommsenstrasse 13, D-01062 Dresden, Germany


β-Chloro-α-cyanocinnamonitrile reacts in an one-pot reaction with potassium thiocyanate and alkanol to form 2-alkoxy-6-phenyl-5-cyano-1,4-dihydro-4-pyrimidinthiones. The products were S-alkylated to yield thieno[2,3-d]pyrimidines on cyclization and aminopyrimidines on substitution of alkoxy and alkylthio groups.

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1169 - 1183
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DOI: 10.3987/COM-98-8133
Electron Impact Induced Fragmentation of 4-Aryl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-diones

Klaus K. Mayer,* Stefan Dove,* Herwig Pongratz, Mevlüt Ertan, and Wolfgang Wiegrebe

*Pharmazeutische Chemie I, Institut für Pharmazie, Universität Regensburg, Universitätsstraße 31, D-93040 Regensburg, Germany


The molecular ions (M+·) of 4-substituted aryl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-diones (Biginelli compounds) (2-18) decompose by loss of the substituents X of the phenyl group (X = o-F; o-, m-, p-Cl, Br, OCH3,CH3; 2,3-, 2,4-, 2,6-, 3,4-dichloro) giving rise to prominent (M - ·X)+ ions at 70 and 12 eV, respectively. In the cases of o-Cl and o-Br substitution, the M is extremely unstable. In general, metastable M (1st ffr) eliminates preferably H·, that of 15 (2,6-dichloro), however, exclusibely a chlorine atom. As corroborated by 2H-labelling, reversible H-migration from C-4 to the phenyl group takes place (1, 1a-1c). The collisional activation spectra of the (M· - X)+ ions of 3 (o-Cl) and 6 (o-Br) are identical but different from the indistinguishable spectra of the (M - ·X)+ ions of 4 (m-Cl), 5 (p-Cl), 9 (o-OCH3), 11 (p-OCH3), and 14 (p-CH3). Semiempirical MO calculations (MOPAC 6.0, PM 3 Hamiltonian) of the M of all ortho-substituted derivatives support a close interaction of o-Cl and o-Br with the carbonyl oxygen, leading to elimination of these substituents and affording cyclic oxonium ions. In th other cases loss of X· is explained as a consequence of 4-H migration to the phenyl group.

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1185 - 1192
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DOI: 10.3987/COM-98-8136
A Novel Synthesis of 1,6-Diamino-2-pyridones and [1,2,4]Triazolo-[1,5-a]pyridine Derivatives

Yoichi Yamada,* Heinosuke Yasuda, and Akiko Takayama

*Department of Chemistry, Faculty of Education, Utsunomiya University, 350 Mine, Utsunomiya 321-8505, Japan


3-Cyano-1,6-diamino-2-pyridone derivatives (3) posessing various alkoxycarbonyl groups are prepared directly from the reaction of dialkyl (E)-2,3-dicyanobutendioates (1) with cyanoacetohydrazide (2). The resulting diamine (3) (R = Et) is readily cyclized to 2-substituted [1,2,4]triazolo[1,5-a]pridine derivatives (5) in high yields by treatment with orthocarboxylic esters (4) such as trimethyl orthoformate or triethyl orthoacetate etc. Furthermore, 3-cyano-6-amino-2-pyridones (6) are although abtained in excellent yields by the reductive deamination of 3. The structural study of 6 was carried out by spectroscopic methods in some details.

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1193 - 1201
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DOI: 10.3987/COM-98-8139
Preparative Scale Conversion of D-Xylose into Hydrophilically Functionalized Pyrazoles

Volker Diehl, Eckehard Cuny, and Frieder W. Lichtenthaler*

*Institut für Organische Chemie, Technische Universität Darmstadt, Petersenstr. 22, D-64287 Darmstadt, Germany


An expeditious, 4-step procedure is described for the conversion of bulk-scale accessible D-xylose into 5-hydroxymethyl-1-phenylpyrazole-3-carboxaldehyde (3), which, in turn, is converted into various pyrazole building blocks with versatile application profiles, such as the 1-phenylpyrazole-3,5-dicarboxylic acid (9), the respective 3,5-dialdehyde (10), and 3,5-bis(aminomethyl)-1-phenylpyrazole (13).

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1203 - 1211
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DOI: 10.3987/COM-98-8144
Synthesis of Pluriaminated Pyridines

Angela De Munno,* Vincenzo Bertini, Nevio Picci, Francesca Iemma, and Marco Pocci

*Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgnimento 35, I-56126 Pisa, Italy


The key reagent 3,5-dichloro-4-pyridinecarbonitrile (1) was used to synthesize 4-aminomethylpyridine derivatives 3,5-disubstituted with various amino groups, very active as inhibitors of diamine oxidase. The study of the reaction allowed to discover conditions for the gradual substitution in good yields of the two chlorine atoms to give symmetrically and unsymmetrically disubstituted derivatives (3), or the substitution of the cyano group, or the formation of amidines. The reduction of the cyano to aminomethyl group in compounds (3) afforded the target bioactive products.

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Paper | Regular issue | Vol 48, No. 6, 1998, pp. 1213 - 1220
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DOI: 10.3987/COM-98-8170
Alternative Synthesis of (-)-Malyngolide Utilizing (-)-Quinic Acid

Keizo Matsuo,* Takuya Matsumoto, and Keiji Nishiwaki

*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan


(-)-Malyngolide, an antibiotic isolated from a blue-green algae, was synthesized starting from (-)-quinic acid.

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Note | Regular issue | Vol 48, No. 6, 1998, pp. 1221 - 1227
Published online:
DOI: 10.3987/COM-98-8115
Synthesis of Pyrazolo[4,3-c]quinoline-5-oxide by Reductive Cyclization of 4-Acetyl-5-(2-nitrophenyl)pyrazole: Revision of the Reported Structures

Genadiy D. Kalayanov and Joong-Kwon Choi*

*Korea Research Institute of Chemical Technology, P.O. Box 107, Yousung, Taejeon, 305-600, Korea


Cyclocondensation of 3-(2-nitrobenzoyl)pentane-2,4-dione with phenylhydrazine provided 4-(2-nitrobenzoyl)-3,5-dimethyl-1-phenylpyrazole (5) instead of 4-acetyl-3-methyl-5-(2-nitrophenyl)-1-phenylpyrazole (2). Catalytic hydrogenation of 2 resulted in the stepwise formation of 3,4-dimethyl-1-phenylpyrazolo[4,3-c]quinoline-5-oxide (3), 3,4-dimethyl-1-phenyl-1H-pyrazolo[4,3-c]quinoline (12), and 3,4-dimethyl-1-phenyl-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (13). Alternate routes for reduction of 5 under different conditions and a facile synthesis of 2 are also described.

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Note | Regular issue | Vol 48, No. 6, 1998, pp. 1229 - 1235
Published online:
DOI: 10.3987/COM-98-8130
Pyrrolo[2,3-d][1,2,3]triazoles as Potential Antineoplastic Agents

Alessandra Passannanti, Patrizia Diana, Paola Barraja, Francesco Mingoia, Antonino Lauria, and Girolamo Cirrincione*

*Instituto Farmacochimico, Università Degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy


Halonitropyrrole (1a) underwent nucleophilic substitution by substituted benzylamines (7) to give the intermediates (8), which by reduction and diazotization followed by an intramolecular coupling reaction led to derivatives of the title ring system (10).

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Note | Regular issue | Vol 48, No. 6, 1998, pp. 1237 - 1248
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DOI: 10.3987/COM-98-8145
New Efficient Synthesis of Ethyl 2,3-Cycloalkenopyridine-4-carboxylate

Ha Young Kim, Sung Hoon Kim, Ghilsoo Nam, Hyenjoo Son, Tae Jo Park, Sook Ja Lee, Jahyo Kang, Dae Yoon Chi,* and Joong Hyup Kim*

*Biochemicals Reserach Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 131-650, Korea


Ethyl 2,3-cycloalkenopyridine-4-carboxylates (6a-c) from 2-chlorocycloalkanone and ethyl cyanoacetate have been synthesized in 4 steps with overall 68, 68, 25% isolation yield for cyclopenteno (6a), cyclohexeno (6b) and cyclohepteno (6c) derivatives, respectively. Pyridine ring is constructed from 1,5-dicarbonyl precursor and nitrogen source. In order to prepare 1,5-dicarbonyl precursor, malonic ester synthesis is used. Alkylation of 2-chlorocycloalkanone (1a-c) with ethyl cyanoacetate affords ethyl cyano-(2-oxocycloalkanoyl)acetate (3a-c). Second alkylation of 3a-c with allyl bromide gives ethyl 2-cyano-2-(2-oxocycloalkanoyl)-4-pentenoate (4a-c). Ozonolysis of olefins (4a-c), and continuously pyridine ring formation with hydroxylamine provides ethyl 2,3-cycloalkenopyridine-4-carboxylate N-oxide (7a-c). This N-oxide is easily reduced with phosphorous trichloride in chloroform. Replacement of hydroxylamine hydrochloride by ammonium foramte as a nitrogen source reduced one step in this process, directly forming 2,3-cycloalkenopyridine-4-carboxylate.

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Note | Regular issue | Vol 48, No. 6, 1998, pp. 1249 - 1254
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DOI: 10.3987/COM-98-8164
Hydrolysis of 4-Amino-3-qunolinesulfonamides

Leszek Skrzypek

*Department of Organic Chemistry, The Medical University of Silesia, Jagiellonska Str. 4, 41-200 Sosnowiec, Poland


Acid hydrolysis of 4-amino-3-quinolinesulfonamides (3) gives 1,4-dihydro-4-oxo-3-quinolinesulfonamides (4), 4-aminoquinolines (5) or a mixture of these compounds.

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Review | Regular issue | Vol 48, No. 6, 1998, pp. 1255 - 1274
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DOI: 10.3987/REV-98-495
Recent Advances in Selective Syntheses of 6- and 7-Substituted Pteridines

Shizuaki Murata,* Kenji Kiguchi, and Takashi Sugimoto

*Human Informatics, Graduate of School, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan


Novel regioselective methods for construction of biologically important pteridines which contain carbon substitution on the 6- or 7-position using pteridine ring-forming cyclocondensations, nucleophilic substitution reactions, and radical reactions are reviewed.

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Review | Regular issue | Vol 48, No. 6, 1998, pp. 1275 - 1290
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DOI: 10.3987/REV-98-497
Acid-catalysed C-3 Epimerization of Reserpine and Other Indolo-[2,3-a]quinolizidines

Mauri Lounasmaa,* Mathias Berner, and Arto Tolvanen

*Laboratory for Organic and Bioorganic Chemistry, Technical University of Helsinki, P.O. Box 6100, FIN-02150 HUT Espoo, Finland


The acid-catalysed C-3 epimerization of the indole alkaloid reserpine (1) and other closely related indolo[2,3-a]quinolizidines is reviewed. The three mechanisms that have been proposed and relevant experimental findings are discussed. Representative examples of C-3 epimerization reactions are included.

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19 data found. 1 - 19 listed