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. 51, No. 7, 1999
Published online:
■ First Electrochemical Defluorination in Heterocyclic Chemistry. Mild Cathodic Reduction of Some Fluoroquinolones
Antonella Profumo, Elisa Fasani, and Angelo Albini*
*Department o f Organic Chemistry, University of Pavia, Via Taramelli 10, 27100 Pavia, Italy
Abstract
Some 7-piperazinoquinolones undergo smooth cathodic defluorination in aqueous buffer (pH 7.2) at -1.35 V vs Ag/AgC1 via an ECE mechanism; a 6-fluoro derivative is reduced, a 6,8-difluoro analogue is selectively reduced at position 8.
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■ The Reaction of 4,5-Epoxy-2(E)-hexenoate and Secondary Amines, Total Synthesis of (-)-Osmundalactone and (-)-Forosamine
Machiko Ono,* Chikako Saotome, and Hiroyuki Akita*
*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
A reaction of methy (4R,5R)-4,5-epoxy-2(E)-hexenoate (1) with N-methylbenzylamine gave a diastereomerically pure (3S,4R,5R)-7 and (4S,5R)-8. The former was chemoenzymatically converted to (-)-osmundalactone (12) which is an aglycone of osmundalin. On the other hand, direct conjugated addition of dimethylamine to methyl (4S,5S)-4,5-epoxy-2(E)-hexenoate (1) followed by treatment with MeOH at 40°C exclusively provided (4R,5S)-17 which was converted into L-forosamine (19).
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■ A Versatile Approach to trans-1,3-Disubstituted Tetrahydro-β-carbolines Using Oxazinanes
Kamajit Singh* and Prasant K. Deb
*Department of Applied Chemical Sciences&Technology, Guru Nanak Dev University, Amritsar-143 005, Punjab, India
Abstract
Under the conditions of thermodynamic control, the diastereoselectivity of the reaction between tryptophan esters and oxazinanes (carbonyl equivalents) can be controlled by incorporating Nb-benzyl substituents; the reaction proceeds in essentially quantitative yield and with trans-diastereoselectivity.
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■ An Efficient Synthesis and Selective Reaction of N-Substituted Isothiazolidinium Salts
Okiko Miyata, Sachiko Yamakawa, Kanami Muroya, and Takeaki Naito*
*Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan
Abstract
The first example of the preparation of N-acylated isothiazolidinium salts is described, and the stability and reactivity of the isothiazolidinium salts are found to be highly dependent upon the substituent at the nitrogen atom.
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■ Synthesis of 1,2-Diazaphenalenes under Microwave
Yousri El Barkaoui, Noura Jorio, Souâd Fkih-Tétouani, Ahmed El Louzi, and André Loupy*
*Laboratoire des Réactions Sélectives sur Supports, C.N.R.S., UMR 8615, Université de Paris-Sud, Batiment 410, 91405 Orsay Cedex, France
Abstract
1,2-Diazaphenalenes were prepared by condensation reactions of hydrazine with isophorone derivatives under various conditions: conventional heating in homogeneous solution and microwave activation either in homogeneous solution or in dry media. Microwave irradiation gave the best results with both enhancements in rates and yields. In many cases, decarboxylation of the heterocycles formed took place. When the reactions were carried out in dry media over K10 montmorillonite, dicondensation products were obtained beside the desired heterocycles.
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■ The Formal Synthesis of Chiral Etodolac Using Chiral 1,2-Di(alkylcarbonyl)oxypentan-3-one as Chiral Building Block
Shan-Yen Chou,* Chin-Lu Tseng, and Shyh-Fong Chen
*Deparatment of Medicinal Chemistry, Development Center for Biotechnology, Hsi-Chih Research Park 101, Lane 169, Kang Ning St, Hsi Chih 221, Taipei Hsien, Taiwan, R.O.C.
Abstract
A stereoselective synthesis of (+)- and (–)-(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)-1-ethanols (31) and (32), the key intermediates for chiral etodolac was executed in seven steps starting from the asymmetric cyclization of (2R)-1,2-di(acetyloxypentan)-3-one (5) or (2R)-1,2-di(propionyloxypentan)-3-one (6) and 7-ethyltryptophol (7). Some unexpected transformations are also described.
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■ Synthesis of 3-Substituted 4-Hydroxyquinolin-2-ones via C-Acylation Reactions of Active Methylene Compounds with Functionalized 3,1-Benzoxazin-4-ones
Christos Mitsos, Alexandros Zografos, and Olga Igglessi-Markopoulou*
*Laboratory of Organic Chemistry, Department of Chemical Engineering, National Technical University of Athens, 9, Heroon Polytechniou St., Zografou Campus, 157 73 Athens, Greece
Abstract
A general protocol for the construction of 4-hydroxyquinolin-2-ones is described. Benzoxazinones react with the anion of active methylene compounds to produce the functionalized C-acylation compounds in very good yields. These key intermediates are cyclized to the desired quinolinones (25-40) under basic conditions. Spectral data and physical characteristics for all compounds are reported.
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■ An Efficient Synthesis of Ofloxacin and Levofloxacin from 3,4-Difluoroaniline
Javier Adrio, Juan C. Carretero,* José L. García Ruano,* Antonio Pallarés, and Mercedes Vicioso
*Departamento de Química Orgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid, Spain
Abstract
The functionalization at either C-2 or C-3 of N-(tert-butoxycarbonyl)-3,4-difluoroaniline based on its ortho-deprotonation under different experimental conditions is described. This kind of products can be readily applied to the synthesis of ofloxacin, levofloxacin and related compounds.
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■ Preparation of 4-(2-Aminoethyl)-3,3-dimethyl-2-piperidone Derivatives by Intramolecular Rearrangement of α,α-Dimethyl-4-piperidineacetyl Chloride
Jean L. Binet,* Corinne Grandvincent, and Didier M. Thomas
*Laboratoires Fournier S. A., Groupe Fournier, 50, Rue de Dijon, 21121 Daix, France
Abstract
Reaction of hindered amines with α,α-dimethyl-4-piperidineacetyl chloride provided 4-(2-aminoethyl)-3,3-dimethyl-2-piperidone derivatives by intramolecular rearrangement of the acid chloride.
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■ Synthesis and Reaction of Dimethyl 7-Bromoindole-2,3-dicarboxylates
Yasuyoshi Miki,* Ko-ichi Matsushita, Hajime Hibino, and Hideaki Shirokoshi
*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan
Abstract
Reaction of 1-(4-benzyloxyphenyl)-2-phenylhydrazine with dimethyl acetylenedicarboxylate (DMAD) gave dimethyl 5-benzyloxyindole-2,3-dicarboxylate and dimethyl indole-2,3-dicarboxylate. However, treatment of 1-(2-bromo-phenyl)-2-phenylhydrazine with DMAD afforded dimethyl 7-bromoindole-2,3-dicarboxylate, exclusively. In a similar manner, dimethyl 7-bromo-5-methoxy-indole-2,3-dicarboxylate was also obtained from 1-(2-bromo-4-methoxyphenyl)-2-phenylhydrazine. The bromo group of dimethyl 7-bromoindole-2,3-dicarboxylate was converted to an 1-ethoxyvinyl or vinyl group by treatment with tributyl-(1-ethoxyvinyl)tin or tributyl(vinyl)tin in the presence of a Pd(0) catalyst.
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■ Synthesis of Cytotoxic Pyrroloquinazolinoquinoline Alkaloid Luotonin A
Zhong-Ze Ma, Yoshio Hano, Taro Nomura,* and Ying-Jie Chen
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
A convenient synthesis of cytotoxic pyrroloquinazolinoquinoline alkaloid, luotonin A (1), was achieved in 3 steps; (i) reaction of anthranilic acid with O-methylbutyrolactim to deoxyvasicinone, (ii) oxidation of deoxyvasiciiione, and (iii) formation of luotonin A by the reaction of vasicinone with anthranyl aldehyde.
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■ Imidazoquinazolinodiones — New Results
Katarzyna Kiec-Kononowicz,* Wolfgang Holzer, and Kurt Mereiter
*Department of Chemical Technology of Drug, Collegium Medicum, Jagiellonian University, ul. Medyczna 9, 30-688 Kraków, Poland
Abstract
X-Ray crystal structure determinations and spectral analyses (NMR, MS) shed new light on the reaction of 5-(Z)-arylidene-2-methylthioimidazolin-4-one (5b) with anthranilic acid, in which apart from the expected 2-(Z)-1-arylidene-2,3,5,10-tetrahydroimidazo[2,1-b]quinazoline-3,5-dione (6b) a new condensed heterocyclic system was identified, i.e. 2-(Z)-arylidene-1,2,4,5-tetrahydroimidazo[1,2-a]quinazoline-1,5-dione (8b). Reaction of the sodium salt of the 4-chioro-substituted arylidene derivative (6a) with methyl iodide surprisingly afforded 2-[(Z)-1-(4-chlorophenyl)methylene]-3-methyl-1,2,3,5-tetrahydroimidazo[1,2-a]quinazoline-1,5-dione (15).
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■ A Tandem C-Acylation-Cyclization Reaction Sequence for the Synthesis of New N-Acyl-3-substituted 1,8-Naphthyridine-2,4-diones
Alexandros Zografos, Christos Mitsos, and Olga Igglessi-Markopoulou*
*Laboratory of Organic Chemistry, Department of Chemical Engineering, National Technical University of Athens, 9, Heroon Polytechniou St., Zografou Campus, 157 73 Athens, Greece
Abstract
The 2-substituted 4H-pyrido[2,3-d][3,1]oxazin-4-ones (1a, b) react with active methylene compounds, under mild conditions, to produce N-acyl-3-substituted 1,8-naphthyridine-2,4-diones (3-12). In addition the C-acylation key intermediates (3a), (13) and (14) have been isolated and subsequently cyclized to the corresponding 3-substituted 1,8-naphthyridine-2,4-diones (3) and (15).
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■ Pyridazines, 90. On the Synthesis of Novel 1,2-Diazine Containing Tricyclic Systems: Preparation of Tetraazaphenazines
Gottfried Heinisch, Elisabeth Huber, and Barbara Matuszczak*
*Institute of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria
Abstract
Reaction of 6-chloro-N-(3,6-dichloropyridazin-4-yl)-3-(4-methoxy-benzyl-amino)-N-propyl-pyridazine-4-carbox-amide (1) under strong basic conditions or with a weak base at high temperature was found to result in a ring contraction to give two isomeric tetra-aza-phenazines. A tentative mechanism is proposed.
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■ The Photochemistry of 2-Diazo- and 3-Diazopyrroles
Silvestre Buscemi,* Andrea Pace, Girolamo Cirrincione, and Patrizia Diana
*Dipartimento di Chimica Organica "E. Paterno", Universita di Palermo, Viale delle Scienze, Parco d'Orleans II, 90128 Palermo, Italy
Abstract
The photochemistry of 2-diazo- and 3-diazopyrroles has been investigated. The irradiation of 2-diazo-3-cyano-4-methyl-5-phenylpyrrole in various reaction solvents brings to a photolytic singlet carbene intermediate, which evolves into 2-substituted pyrroles. A substituent effects has been recognized in the irradiations of some 3-diazopyrroles in methanol.
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■ Cyclic Dipeptides. 4. On the Pummerer Rearrangement of Diastereomeric Dehydrocyclolanthionine Sulfoxides
Angela Crescenza, Maurizio Botta,* Federico Corelli,* and Andrea Tafi
*Dipartimento Farmaco Chimico Technlogico, Università degli Studidi Siena,Banchi di Sotto, 55 - 53100 Siena, Italy
Abstract
Ring transformation and functionalization of dehydrocyclolanthionine sulfoxides by Pummerer rearrangement, leading to different compounds depending on the experimental conditions, are described.
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■ A cis-Languidulane Diterpenoid from Salvia mexicana var. major (Labiatae)
Baldomero Esquivel,* Noemi Ramírez-Dávalos, and Georgina Espinosa-Pérez
*Instituto de Química, Universidad Nacional Autónama de México, Circuito Exterior, Ciudad Universitaria, Coyoacán 04510 Mexico, D.F., Mexico
Abstract
A new cis-languidulane diterpenoid, named Salvimexicanolide has been isolated from the aerial parts of Salvia mexicana var. major besides the known flavonoid naringenin. The structure of the new diterpenoid was established by spectroscopic methods and confirmed by X-Ray analysis.
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■ New Briarane Diterpenes from a Gorgonacean Briareum sp.
Tetsuo Iwagawa,* Keita Takayama, Hiroaki Okamura, Munehiro Nakatani,* and Matsumi Doe*
*Department of Chemistry and Bioscience, Faculty of Science, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan
Abstract
Five new diterpenes violides C (1)-I (7), possessing a 2,3,4-, 2,3-, and 2,4-oxidized briarane skeleton have been isolated from a gorgonacean Briareum sp. Their structures were established by spectral methods.
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■ Synthesis, Reactivity and 13C-NMR of 1H-Pyrazolo[3,4-c]pyridine Derivatives
Jean-Claude Milhavet, Alain Gueiffier,* Lysiane Bernal, and Jean-Claude Teulade
*Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, U.F.R. des Sciences Pharmaceutiques "Philippe Maupas", Université de Tours, 31Avenue Monge, 37200 Tours, France
Abstract
The synthesis of various 1H-pyrazolo[3,4-c]pyridines was reported. 3-Cyano derivatives were obtained from the corresponding nitro compounds by Sandmeyer Reaction using Na3[Cu(CN)4] at pH 1. The 13C-NMR data of this serie were also described.
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■ A Chemical Evidence of Regiochemistry in the Diels-Alder Reaction of 4-Oxygenated Quinolinequinones with 1-Methoxy-3-trimethylsilyloxy-1,3-butadienes
Yoshie Horiguchi, Katsuhiro Tomoda, and Takehiro Sano*
*Showa College of Pharmaceutical Sciences, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Abstract
The synthesis of four regioisomeric azaanthraquinones (4a, b and 5a, b) was achieved in a regioselective manner by the Diels-Alder reaction of 4-oxygenated 6-bromo- and 7-bromoquinolinequinones (11 and 15) with 1-methoxy-3-trimethylsilyloxy-1,3-butadiene. The results gave a chemical evidence of the regiochemistry observed in the Diels-Alder reactions of non-halogenated 4-oxyquinolinequinones (1a and 1b) which showed an inverse regioselectivity.
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■ Recent Developments on the Chemistry and Biological Activity of Artemisinin and Related Antimalarials — An Update
Asish K. Bhattacharya and Ram P. Sharma*
*Phytochemical Technology Division, Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow 226015, India
Abstract
Developments taken place in the field of artemisinin and related anti-malarials during the last seven years have been reviewed.