HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Regular Issue
Vol. 53, No. 4, 2000
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■ Trapping of Unsaturated Fulvene Endoperoxides with Dimethyl 1,2,4,5-Tetrazine-3,6-dicarboxylate: A New Synthesis of Alkylidene- and Arylidenemalonaldehydes
Galip Özer, Nurullah Saraçoglu, and Metin Balci*
*Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Abstract
Unsaturated fulvene endoperoxides (2a-e) were trapped with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (4). The formed saturated fulvene endoperoxides containig 1,2-dihydropyridazine ring (6a-e) were characterised by spectroscopic methods. Treatment of (6a-e) with cobalt(II) tetraphenylporphyrin (CoTPP) provided alkylidene- and arylidenemalonaldehydes (9a-e).
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■ Convenient Synthesis of a 2,3,6-Tristhiazolylsubstituted Pyridine Skeleton [Fragment A-C] of a Macrocyclic Antibiotic, GE 2270 A
Kazuo Okumura, Taishi Suzuki, and Chung-gi Shin*
*Laboratory of Organic Chemistry, Faculty of Technology, Kanagawa University, Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan
Abstract
Convenient synthesis of the 2,3,6-tristhiazolylsubstituted pyridine skeleton [Fragment A-C] of a macrocyclic antibiotic, GE 2270 A, was first achieved from a chiral 2-(2-{2-[(1R,2S)-(1-amino-2-hydroxy-2-phenyl)ethyl]-thiazol-4-yl}thiazol-4-yl)pyridine derivative [Fragment A] and H-L-Ser-L-Pro-NH2 as the precursor of Fragment C.
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■ Asymmetric Syntheses of (+)-Camptothecin and (+)-7-Ethyl-10-methoxycamptothecin
Keiko Tagami, Norio Nakazawa, Shigeki Sano, and Yoshimitsu Nagao*
*Faculty of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Abstract
Total syntheses of (+)-camptothecin (1a) and (+)-7-ethyl-10-methoxycamptothecin (1b) from racemic ethyl 1-ethoxycarbonyl-3-oxopyrrolidin-2-ylacetate (7) were accomplished via asymmetric hydroxylation onto C20 of racemic 20-deoxycamptothecin derivatives (3a,b) employing a chiral Davis reagent, (2R, 8aS)-(+)-(camphorylsulfonyl)oxaziridine.
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■ Total Syntheses of Kurasoins A and B, Novel Protein Farnesyltransferase Inhibitors, and Absolute Structures of Kurasoins A and B
Tomoyasu Hirose, Toshiaki Sunazuka, Tian Zhi-Ming, Masaki Handa, Ryuji Uchida, Kazuro Shiomi, Yoshihiro Harigaya, and Satoshi Omura*
*Research Center for Biological Function, The Kitasato Institute and School of Pharmaceutical Sciences, Kitasato University, Shirokane, Tokyo 108-8642, Japan
Abstract
Asymmetric total syntheses of kurasoins A (1) and B (2), recently discovered protein farnesyltransferase (PFTase) inhibitors, have been achieved in seven steps from 2-(4-hydroxyphenyl)ethanol via the stereospecific alkylation of the chiral epoxide ((-)-7) and in four steps from phenylacetaldehyde via the coupling reaction of the chiral epoxide ((-)-13) with indole, respectively. The synthesis defined the (3S) absolute configuration of 1 and 2. The stereochemistry of the hydroxy group is important for eliciting PFTase inhibition.
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■ Synthesis of New Spiro-N -heterocycles with Cyclooctane Fragment from N -(1-Alkenylcyclooctyl)-N -aryl(benzyl) Amines
Leonor Vargas M., Wilson Rozo, and Vladimir Kouznetsov*
*Laboratory of Fine Organic Synthesis, School of Chemistry, Industrial University of Santander, A.A. 678, Bucaramanga, Colombia
Abstract
The homoallylic amines (6-10) derived from N-cyclooctylidenearyl (benzyl)amines and allyl- or prenylmagnesium bromides as organometallic reagents have been used for synthesis of spiro-N-heterocycles. The tetrahydrospiro[3H-2-benzazepine-3,1’-cyclooctanes] (11 and 12) have been obtained from the homoallylamines (6 and 7) under acidic conditions. The tetrahydro-1-benzazepine (15) spiroannulated with a cyclooctane moiety has been prepared by treating the homoallylic amine (9) with conc. sulfuric acid. Treatment of the homoallylmine (6) with 92% sulfuric acid in chloroform at reflux afforded tetrahydrospiro[1,2,3-oxathiazine-2,2-dioxide-4,1’-cyclooctane] (17). The latter has been converted into 1-benzyl-4-methylspiro[azetidine-2,1’-cyclooctane] (18). The homoallylamine (6) has been cyclized into the 1-benzylspiro[pyrrolidine-2,1’-cyclooctane] (19).
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■ Synthesis of 4-[4’-(N,N-Dimethylsulfamoyl)piperazin-1-yl]pyridine Derivatives as Sorbitol Dehydrogenase Potential Inhibitors
Didier Varlet, Eric Fourmaintraux, Patrick Depreux, and Daniel Lesieur*
*Institut de Chimie Pharmaceutiqe, Université de Lille 2, rue du Professeur Laguesse, 59006 Lille, France
Abstract
A synthesis of various pyridines disubstituted in position 4 by a [4’-(N,N-dimethylsulfamoyl)piperazin-1-yl] group and in position 2 by different functionalities such as hydrogen, hydroxymethyl, formyl, carboxamido or cyano, is described.
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■ A Synthesis and Transformations of Alkyl 2-[2-Cyano-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopropenoates. A One-Pot Synthesis of Pyrrolo[3,2-d ]pyrimidin-4-ones
Lucija Jukic, Jurij Svete, Amalija Golobic, Ljubo Golic, and Branko Stanovnik*
*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, 1000 Ljubljana, Slovenia
Abstract
Alkyl 2-[2-cyano-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopro-penoates (8) and (9) were transformed by heating into alkyl 2-[2-cyano-2- (2-pyridinyl)ethenyl]amino-3-[2-methoxycabonyl-4-(2-pyridinyl)-1H-pyrrol-3-yl]aminopropenoates (12) and (13). Compounds (8) and (9) can be transformed in the presence of primary aliphatic amines into substituted pyrrolo[3,2-d]pyrimidines (17-19).
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■ Stereochemical Aspects during Addition Reaction of 2-Cyano-1,2-dihydroisoquinolines with Bromine in Methanol with and without Pyridine
Michiharu Sugiura,* Koosuke Asai, Keiichiro Hatano, Yukihisa Kurono, and Yoshiki Hamada
*Faculty of Pharmacy, Meijo University, Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan
Abstract
2-Cyano-1-methoxy-1,2-dihydroisoquinoline (3) treated with bromine in methanol gave 4-bromo-2-cyano-1,3-dimethoxy-1,2,3,4-tetrahydroisoquinolines (4) exhibiting two configurational isomers (4a and 4b). During repeated recrystallization of 4a, auto-hydrolysis led it to 1-demethylation product (6), whereas 4b was intact giving single crystals. The structures of 4b and 6a were determined by X-Ray crystallography. 2-Cyano-1-hydroxy-1,2-dihydroisoquinoline (7) treated with bromine in methanol containing pyridine gave 6a stereoselectively in high yield, whereas from 3 compounds (4a) and (4b) were afforded in a product ratio of 1 : 1. The mechanisms for the 4a and 4b interconvertible reaction and also for the reaction from 7 to 6a were examined.
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■ Dipolarophilic Behavior of the Isoxazole Ring in Intramolecular Nitrilimine Cycloadditions
Gianluigi Broggini, Luisa Garanti, Giorgio Molteni,* and Gaetano Zecchi
*Dipartimento di Chimica Organica e Industriale dell'Università and Centro CNR, Via Golgi 19, 20133, Milano, Italy
Abstract
Upon base treatment with silver carbonate, isoxazolyl-substituted hydrazonoyl chlorides (4) and (12) undergo a sequential intra- intermolecular nitrilimine cycloaddition giving tetracyclic pyrazolydine derivatives (7) and (15).
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■ Electrochemical Synthesis of 2-Aryl-2H -benzotriazoles and Their N -Oxides by Controlled Potential Cathodic Electrolysis
Byeong Hyo Kim,* Doo Byung Lee, Dae Ho Kim, Rongbi Han, Young Moo Jun, and Woonphil Baik
*Department of Chemistry, Kwangwoon University, Seoul, 139-701, Korea
Abstract
Using a divided cell, reductive cyclizations of o-nitrophenylazo dyes (1) toward 2-aryl-2H-benzotriazole-1-oxides (2) or 2-aryl-2H-benzotriazoles (3) were successfully accomplished by the controlled potential cathodic electrolysis reactions. 1 was transformed to 2 under neutral conditions while 1 was transformed to 3 under basic conditions.
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■ Dioximes as Synthons for Medium Ring Heterocyclic Compounds
Maya Shankar Singh* and Ashwani Kumar Singh
*Department of Chemistry, D. D. U. Gorakhpur University, Gorakhpur-273 009 (U. P.), India
Abstract
A simple and convenient synthetic approach to eight-, nine- and ten-membered nitrogen and oxygen containing heterocycles has been developed. 3,4-Diaryl-1,6,2,5-dioxadiazocines, (3) and (4), 3,4-diaryl-1,6,2,5-dioxadiazonines,(5) and 3,4-diaryl-1,6,2,5-dioxadiazacyclodeca-2,4-dienes (6) are prepared in one-pot from vicinal dioximes (1) via dianion intermediate (2) and 1,2-dibromoethylene, l,2-dichloroethane, 1,3-dibromopropane and 1,4-dichlorobutane, respectively. A plausible mechanism has bcen discussed.
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■ 1,3-Dipolar Cycloaddition between Hetaryl Nitrones and Methyl Acrylate: Theoretical Study and Application to the Synthesis of Functionalized Pyrrolidines
Pedro Merino,* Sonia Anoro, Francisco Merchan, and Tomas Tejero
*Departamento de Quimica Organica, Facultad de Ciencias, ICMA, Universidad de Zaragoza, E-50009 Zaragoza, Aragon, Spain
Abstract
The 1,3-dipolar cycloaddition reaction of N-benzyl-C-(hetaryl)nitrones gave preferentially trans-substituted 3,5-disubstituted isoxazolidines (endo approach) which can be further converted into the corresponding 5-hetaryl-3-hydroxy-2-pyrrolidinones. A theoretical study of the cycloaddition reaction by using both semiempirical (AM1, PM3) and ab initio (HF/3-21G, HF/6-31G*//3-21G) methods has also been carried out. In all cases the obtained results are in good qualitative agreement with the experimental observations.
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■ Mechanism on One-sided Wessely-Moser Rearrangement Reaction
Kazuki Shinomiya, Yoshio Hano, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Wessely-Moser rearrangement reaction of 5,7-dihydroxychromone derivatives with an isopentyl side chain at C-6 or C-8 position was examined. All reactions gave 8-isopentylchromone derivative predominantly as rearrangement product. Kinetic analysis of the one-sided rearrangement reaction revealed that the reaction depends on stability of a flavylium cation originated from 8-isopentylchromone derivative.
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■ Stereoselective Synthesis of 1,4-Dideoxy-1,4-imino-L-lyxitol and 1,5-Dideoxy-1,5-imino-D-ribitol
Ki Chang Jang, Ill-Yun Jeong, Min Suk Yang, Sang Uk Choi, and Ki Hun Park*
*Department of Agricultural Chemistry, Gyeongsang National University, Chinju, 660-701, Korea
Abstract
1,4-Dideoxy-1,4-imino-L-lyxitol (2) and 1,5-dideoxy-1,5-imino-D-ribitol (3) were prepared from allylic alcohol (1) derived from D-glucono-δ-lactone. Key transformation includes diastereoselective epoxidation of (1) with m-CPBA.
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■ Easy Access to Medium Rings by Entropy/Strain Reduction, Part 4. A Simple and Mild Route to Some Substituted 2,7-Dihydro-1H -oxepins, thiepins and a Phosphepin
James G. Walsh and Declan G. Gilheany*
*Department of Chemistry, National University of Ireland, Maynooth, Co. Kildare, Ireland
Abstract
Reaction of substituted 1,6-dibromohexa-2,4-dienes (3) with sulfide ion leads to the corresponding dihydro-1H-thiepins (5) which were characterised as their sulfones 6. Reaction of 3 with dichlorophenylphosphine in the presence of sodium gives a low yield of dihydro-1H-phosphepin oxide (7). Reaction of the 1,6-diols (2) with butyllithium and p-toluenesulfonyl chloride gives the dihydro-1H-oxepins (8).
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■ Reactivity of Heterocyclic Enaminones: Regioselective Synthesis of Polyfused Indolones
Yves Blache,* Véronique Benezech, Jean-Michel Chezal, Pierre Boule, Henri Viols, Olivier Chavignon, Jean-Claude Teulade, and Jean-Pierre Chapat
*Laboratoire de Chimie Organique Pharmaceutique, E. A. 2414, 15 Avenue Charles Flahault, Faculté de Pharmacie, 34060 Montpellier, France
Abstract
Photocyclization of heterocyclic enaminones to give partial hydrogenated derivatives of indolo[2,3-c]quinoline, pyrido[2,3-c]carbazole, and pyrido[4,3-a]carbazole is described. In addition, 3-[(5’-quinolinyl)- benzylamino]cyclohex-2-en-1-one and 3-[(8’-quinolinyl) benzylamino]cyclohex-2-en-1-one undergo C-N bond cleavages and a benzyl migration on the C-6 and C-7 positions respectively.
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■ Nitrilimine Cycloadditions onto Partially Saturated Furo[3,4-c]thieno[2,3-d]pyrazoles. A Problem in Site Selectivity
Gianluigi Broggini, Luisa Garanti,* Giorgio Molteni, and Gaetano Zecchi
*Dipartimento di Chimica Organica e Industriale dell’Università and Centro CNR, Via Golgi 19, 20133 Milano, Italy
Abstract
Partially saturated furo[3,4-c]thieno[2,3-d]pyrazoles (7-10) have been submitted to 1,3-dipolar cycloaddition with a variety of nitrilimines. The competitive formation of products due to the dipolar attack at different dipolarophilic sites has been observed. The experimental evidence is discussed by taking into account electronic features of the reactive species as well as their steric encumbrance.
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■ A Novel and Convenient Synthesis of 1,3,5-Triazine-2,4(1H ,3H )-diones
Isao Shibuya,* Kazumasa Honda, Yasuo Gama, and Masao Shimizu
*National Institute of Materials and Chemical Research, 1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
Abstract
Several 1,3,5-triazine-2,4(1H,3H)-diones (1-5) were newly synthesized by the reaction of N-substituted thiocarboamides with silver cyanate. The structure was confirmed by the X-Ray structure analysis, and the pathway affording them was estimated.
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■ Synthesis of Heteromine C from Guanine
Erik Jakobsen and Lise-Lotte Gundersen*
*Department of Chemistry, University of Oslo, P.O.Box 1033, Blindern, N-0315 Oslo, Norway
Abstract
Heteromine C previously isolated from a Taipei folk medicine plant, has been synthesised for the first time by selective methylation reactions starting from guanine. Thermal rearrangement to 1-methylherbipoline takes place when heteromine C is heated. It is shown that treatment of O6,9-dimethylguanine with methyl iodide gives the O6,7,9-trimethylguaninium iodide with complete selectivity, while similar reaction on O6,7-dimethylguanine results in methylation both in the 3- and 9-position.
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■ β-Halovinylaldehydes - As Versatile Reactive Intermediates in the Syntheses of Condensed Fused Ring Polycyclic Heterocycles
Batchu Chandra Sekhar,* Sukuru Raghu Ramadas, and Devella Venkata Ramana
*Department of Chemistry, Indian Institute of Technology, Chennai - 600 036, India
Abstract
New approaches for the syntheses of a wide range of mono and polycyclic heterocycles utilizing β-halovinylaldehydes are summarized. The syntheses of a variety of heterocycles employing this synthon are discussed vividly in this review with 80 reference citations.