HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Gilbert Stork's Special Issues, Vol. 25, No. 1, 1987
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■ Intramolecular Ene Reaction: The Use of 1,7-Enynes in the Synthesis of Hydroxylated Methlenecyclohexane Derivatives
Jacqueline Ficini, Claude Barbara, Didier Desmaële, and Ouathek Ouerfelli
*Laboratoire de Chimie Organique de Synthèse, UA 408, Université P. et M. Curie, 8, rue Cuvier 75005 Paris, France
Abstract
The intramolecular ene reaction of 1-7 enynes produces on a preparative scale methylene cyclohexanes in good yields wnen the double bond is trisubstituted. A protected 1-3 dihydroxy enyne reacts in the same way.
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■ New Slow Release Application Techniques with Heterocyclic Herbicides in Aquatic Weed Control
Müfit Bahadir and Friedhelm Korte
*Lehrstuhl für Makromolekulare Stoffe, Institut für Chemie , Technische Universität München, Lichtenbergstrasse 4, D-85747 Garching, Germany
Abstract
Slow release formulations of s-triazine derivatives were prepared by extrusion of EVA copolymers with 1 and 2. Diffusion coefficients of the compounds in the matrix were measured for 1 as D0=0.39·10-9 cm2·s-1 and for 2 as D0=0.81·10-9 cm2·s-1. Slow release formulation of 2 showed a strongly herbicidal activity with a long duration in controlling Lemna minor in a laboratory flow system as well as Eichornia crassipes, Salvinia molesta and Pistia stratiotes under outdoor conditions.
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■ Glycosylation of Silyl Ethers: A Novel Synthesis of Oligosaccharides and Aryl Glycosides
Vijay Nair and Joseph P. Joseph
*Medical Research Division, Lederle Laboratories, American Cyanamid Company, Pearl River, NY 10965, U.S.A.
Abstract
A novel procedure for the synthesis of oligosaccharides and aryl glycosides involving the glycosylation of silyl ethers is described.
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■ A Novel "Ring-switching" Amination: Conversion of 4-Amino-5-cyanopyrimidine to 4,6-Diamino-5-cyanopyrimide
Edward C. Taylor, Wendell A. Ehrhart, Clive O. S. Tomlin, and Jang B. Rampal
*Department of Chemistry, Princeton University , Princeton, New Jersey 08544, U.S.A.
Abstract
4-Amino-5-cyanopyrimidine is “aminated” to 4,6-diamino-5-cyanopyrimidine by a ring-switching process involving ring closure with formamidine acetate to 4-sminapyrimido(4,5-d)pyrimidine, acidic hydrolysis to 4,6-diaminopyrimidine-5-carboxaldehyde, conversion of the latter to its oxime and dehydration.
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■ Functionalized Enamines in the Synthesis of Some Heterocyclic Compounds
Ljubo Golic, Crtomir Stropnik, Branko Stanovnic, and Miha Tisler
*Department of Chemistry, E. Kardelj University, Murnikova 6, 61000 Ljubljana, Slovenia
Abstract
Esters of 3-amino-2-cyanoacrylate and analogous compounds were used as starting material for pyridines which were obtained via the corresponding amidines. On the other hand, from ethyl 5-arninoisoxazole-4-carhoxylate or 5-amino-4-cyanoisoxazole in a similar reaction sequence a pyrimidine derivative could be prepared.
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■ Novel (±)-1-Phenyltetrahydroisoquinolines and 1-Phenylisoquinoline: Potential Intermediates in Alkaloud Synthesis
Bindumadhavan Venugopalan and Arnold Brossi
*Laboratoryof Chemistry, Medical Chemistry Section, National Arthritis Institute, National Institute of Health, Behesda, Maryland 20892, U.S.A.
Abstract
Synthesis of several novel (±)-1-phenyltetrahydroisoquinolines and 1-phenylisoquinolines, srructurally related to the 1-benzylisoquinoline alkaloids norreticuline, reticuline, tetrahydropapaveroline and papaverine, by the Bischler-Napieralski route is reported.
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■ The Structures of Four New C19-Diterpenoid Alkaloids from Aconitum forrestii Stapf
S. William Pelletier, Balawant S. Joshi, Jan A. Glinski, Hitesh P. Chokshi, Szu-ying Chen, Krishna Bhandary, and Kuantee Go
*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.
Abstract
From the root extracts of Aconitum forrestii Stapf, we have isolated four new alkaloids: acoforine (6), acoforesticine (8), acoforestine (10) and acoforestinine (14), besides crassicauline A, forestine and yunaconitine. The structures of these alkaloides were determined on the basisi of spectral data and correlation with alkotoids of established structures. The structure and stereochemistry of acoforestine (10) was confirmed by an X-ray crystal structuer determination.
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■ The Total Synthesis of Lycopodine Using Bridgehead Intermediates
George A. Kraus and Yung-Son Hon
*Department of Chemistry, Iowa State University, Ames, Iowa 50011, U.S.A.
Abstract
The total synthesis of lycopodine has been achieved by two different routes. In one route a bridgehead carbocation is trapped by 3-benryloxy-1-propanamine. In the second route a bridgehead enone is generated in situ and reacted with 3-hydroxy-1-propanamine.
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■ Termal Base-induced Rearrangement of a Pyridinium Salt to an Azepine
Alan R. Katritzky, Jose M. Aurrecoechea, Keping Quian, Anna E. Koziol, and Gus J. Palenik
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.
Abstract
Heating 1-benzyl-2,4,6-triphenylpyridinium tetrafluoroborate in the presence of strong base results in formation of 3H-2,4,6,7-tetraphenylazepine. The spectral data and crystal structure are discussed.
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■ Base-induced Ring Cleavage of 4-Functionalized 3-Unsubstituted Isoxazoles. Synthesis of 2-Aminopyrimidines and Pyrimidine-2(3H)-thiones
Angel Alberola, Luis F. Antolín, Ana M. González, Miguel A. Laguna, and Francisco J. Pulido
*Deparamento de Química Orgánica, Facultad de Ciencias, Universidad de Valladolid, 47005 Valladolid, Spain
Abstract
4-Functionalized 3-unsubstituted isoxazoles undergo ring cleavage when treated with bases. The rtsulting open chain products (β-cyanoenolates, β-enaminonitriles) were converted into pyrimidines, pyrimidinethiones and pyridinones by reaction with 1,3-dinucleophiles (guanidine, thiourea) and compounds having activated methylene groups.
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■ Conjugate Addition of Furans to Enones or Their Synthetic Equivalents
Jean-Marie Poirier and Gilles Dujardin
*IRCOF, URA DO 464 CNRS, Faculté des Sciences de Rouen, Université de Rouen, 76821 Mont Saint-Aignan Cedex, France
Abstract
Conjugate addition of furans 5 to enones 3, in the presence of an alcohol and boron trifluoride etherate is described. A same reaction product is obtained with hemiacetal vinylogs 1, synthetic equivalents of enones 3. Acidic treatment of adducts 6 and 7 leads to tri- and tetraketones 15 and 16.
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■ A Biogenetically Patterned Synthesis of Deoxycryptopleuridine
Richard B. Herbert, Eric Knagg, Helen M. Organ, Vinayager Pasupathy, and David S. Towlson
*Department of Organic Chemistry, University of Leeds, Leeds LS2 9JT, U.K.
Abstract
The synthesis of two octahydroquinolizines (11) and (13) has been achieved following a biogenetically-patterned route. Oxidative cyclisatian of (11) and (13) using thallium(III) trifluoroacetate gave the phenanthroquinolizidines (4) and (6), respectively, and also surprisingly (16) and (17), respectively. Careful comparison of the 1H nmr spectra of (4) and (6) with those of the alkaloid crytopleuridlne and its acetate allowed confirmation that (2) is the correct structure for the alkaloid cryptopleuridine.
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■ Stereoselective Synthesis of 1,2-Diethoxy- and 1,4-Dioxino[2,3-b]furans Using Organoiron Reagents
Myron Rosenblum, Bruce M. Foxman, and Mark M. Turnbull
*Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454-9110, U.S.A.
Abstract
Use of the readily available organoiran complexes 3 and 13 for the stereoselective synthesis of 2,3-dialkoxytetrahydrofurans is reported. The novel tricyclic diaxinafuran 17 can be prepared from complex 13a, while 13b yields the related. optically active 20 ([α]20D = +57.04°), with defined absolute configuration at 6-centers.
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■ C-Morpholino- or Piperidino-v-triazoles from 1,1-Enediamines and Ethyl Azidoformate
Stefania Fioravanti, Maria Antonietta Loreto, Lucio Pellacani, and Paolo Antonio Tardella
*Piazza Aldo Moro, 5 - 00185 Roma, Università a degli Studi di Roma "La Sapienza", Piazza Aldo Moro, 5 - 00185 Roma, Italy
Abstract
Ethyl azidoformate adds instantaneously to 1,1-enediamines at low temperature and the expected triazolines undergo easily a rare elimination of N-ethoxycarbonylamines to give C-morpholino- or piperidino-v-triazoles - in yields ranging from 50 to 70%.
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■ Enantioselective Total Syntheses of Sibirine, Nitramine, and Isonitramine
Partick J. McCloskey and Arthur G. Schultz
*Department of Chemistry, Rensselaer Polytechnic Institute, Troy, New York 12181, U.S.A.
Abstract
The stereoselective Birch reductive alkylation strategy has provided total syntheses and configurational assignments for the 1-azaspiro[5.5]undecane alkaloids sibirine (1), isonitramine (2), and nitramine (3).
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■ The Invention of New Radical Chain Reactions. Part XIII. High Yielding Decarboxylative Chalcogenation of Aliphatic and Alicyclic Acids
Derek H. R. Barton, Dominique Bridon, and Samir Z. Zard
*Institut des Chimie des Substances Naturelles, C.N.R.S., 1 avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France
Abstract
Irradiation with a tungsten lamp of mixed anhydrides (e.g. 8) derived from aliphatic or alicyclic carboxylic acids and N-hydroxy-2-pyridine thione 3 in the presence of a disulphide. diselenide or ditelluride gives the corresponding chalcogenide (e.g. 9, 10, or 11) in high yield. The process involves a radical decarboxyiation followed by SH2 reaction of the intermediate carbon radical on the dichalcogenide.
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■ The 2,2’-Spirobichroman-1,1’-spirobiindan-4,4’-diol Rearrangement. II
Tsuguo Tanaka, Masao Miyaguchi, Rosalina K. Mochisuki, Senichiro Tanaka, Masayo Okamoto, Yoshifumi Kitajima, and Toru Miyazaki
*Faculty of Science and Engineering, Saga University, Honjo 1, Saga, Saga 840-8502, Japan
Abstract
The reaction of 2,2’-spirobichroman derivatives with either hydrobromic acid in the acetic acid solution or aluminium chloride in the chlarobenzene solution yielded 1,l’-spirobiindan-4,4’-diol analogues. The reaction is peculiar as campared with the reaction of alkyl aryl ethers with the same reagents in the same media.
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■ Bicycloannulation of 3-Indolylenamines with Cyclohexenone: A Facile Preparation of Potential Neurotransmitter Analogs
Matthew F. Schlecht and Salvatore Giandinoto
*Department of Chemistry, Princeton University , Princeton, New Jersey 08544, U.S.A.
Abstract
Enamines of 3-indolylacetaldehyde undergo bicycloannulation with cyclohexenone to yield disubstituted bicyclo[2.2.2]octanones. and the mechanistic implications of the product stereochemistry are discussed. Wolff-Kishner reduction gives the corresponding disubstituted bicyclo[2.2.2]octane. Preliminary screening shows that these compounds may exhibit activity as neurotransmitter analogs.
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■ Synthesis and Conformational Studies of 4-Carbamoyl-1-[2-(hydroxymethoxy)methyl]-5-(methylamino)imidazole and Derivatives as New Acyclonucleosides Analogues
George I. Birnbaum, Erik de Clercq, Peter W. Hatfield, and Morris J. Robins
*Division of Biological Sciences, National Research Council of Canada, Montreal Road Compus, Ottawa, Ontario, K1A 0R6, Canada
Abstract
Crystals of the title compound (3) belong to the orthorhombic space group Pbc21 with a = 8.718(1), b = 8.718(1), b = 18.351(2), c =12.570(2) Å. The structure was determined by direct methods and refined by least squares to a final value of R = 0.048. Two independent molecules were found in the asymmetric unit, each in a different conformation. Infrared and 1H nmr spectral evidence was compatible with intramolecular hydrogen bonding of the NH2 group of the 4-carbamoyl function (to N3 in both crystallographically independent molecules). However, no evidence for defined conformations of the 5-methylamino group or the acyclic side chain at N1 was found in the solution studies. 1H nmr spectra of the 5-(N-acetyl-N-lmethylamino) derivatives (5 and 6) of 3 showed restricted rotation of the side chain. Conjugation of the 4-carbamoyl and 5-methylamino groups was apparent in the solid-state conformers and also from uv spectra of 5 and 6. Biological evaluation of 3 and its 5-desmethyl analogue in viral infected, neoplastic, and normal control mammalian cell cultures showed no inhibitory or cytotoxic effects at the highest concentrations tested.
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■ Synthesis of Multi-13C-enriched Methotrexate for NMR Studies of Drug — Enzyme Interactions
H. T. Andrew Cheung, Mary Smal, and Diem Dieu Chau
*Department of Pharmacy, University of Sydney, Sydney, N. S. W., Australia
Abstract
Methotrexate. N- [p-(2,4-diaminopteridin-6-yl)methyl(methyl) - aminobenzoyl]-L-glutamic acid, 13C-enriched at positions 6; 2,7,9: 4,7,8a,9; and 2,4a,6 were synthesized from the correspondingly labelled 2,4-diamino- 6-methylpteridine4 by ‘benzylic’ bromination follwed by displacement of the bromide by di-t-butyl N-(p-methylaminobenzoyl)-L-glutamate. Acid treatment of each methotrexate di-t-butyl ester formed yielded the corresponding 13C-enriched methotrexate.
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■ Synthesis of Cephalotaxine Analogs
Richard K. Hill, Seiji Sawada, Mark G. Bock, and Joseph R. Greene
*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.
Abstract
The efficient preparation of a pentacyclic analog 4 of the cephalotaxine skeleton is described.
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■ Synthesis of Chiral Cyclohexanes from Levoglucosenone and Its Application to an Indole Alkaloid Reserpine
Minoru Isobe, Naoki Fukami, Toshio Nishikawa, and Toshio Goto
*Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan
Abstract
The synthetic studies directed toward an indole alkaloid reserpine 1 is described in the form of 40 as optically active manner starting from Diels-Alder cycloaddition to a carbohydrate derivative, levoglucosenone 3.
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■ Increasing the Racemase Activity versus Transaminase Activity of a Pyridoxal Enzyme Model by the Attachment of a Rigid Base
Jean Chmielewski and Ronald Breslow
*Department of Chemistry, Columbia University, 3000 Broadway, Mail Code 3114, New York, New York 10027, U.S.A.
Abstract
A pyridoxal carrying a 2-pyridylactylate group catalyzes the racemization of L-alanine. Comparison with related compounds shows that this rigid basic sidearm increases the selectivity for racemization relative to transamination.
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■ Synthesis of Diepoxides and Diaziridines, Precursors of Enantiomerically Pure α-Hydroxy and α-Amino Aldehydes or Acids, from D-Mannitol
Yves Le Merrer, Annie Duréault, Christine Greck, Dominique Micas-Languin, Christine Gravier, and Jean-Claude Depezay
*U.A.400, C.N.R.S., Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université René Descartes, 45 rue des Sts Pères 75270 Paris, France
Abstract
Specific activations or protections of the hydroxyl groups of 3-4-0-isopropylidene-D-mannitol 2 followed by intramolecular SN2 reactions, lead to the chiral diepoxides 4 and 7 and to the chiral diaziridines 9 and 13 precursors of enantiomerically pure α-hydroxy and α-amino aldehydes or acids.
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■ Base-assisted Migration of Trimethylsilyl Group from Carbon to Oxygen in γ-Trimethylsilyl-γ,δ-unsaturated Alcohols, γ-Trimethylsilyl-γ,δ-epoxy Alcohols, and β-Trimethylsilyl-β,γ-epoxy Alcohols to the Corresponding Silyl Ethers
Yuichi Kobayashi, Hiroshi Uchiyama, Hiroshi Kanbara, Masato Kusakabe, and Fumie Sato
*Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan
Abstract
Treatment of γ-trimethylsilyl-γ,δ-unsaturated alcohols 2, γ-trimethylsilyl-γ,δ-epoxy alcohols 3-6, and β-trimethylsilyl-β,γ-epoxy alcohols 9-12 with NaH in HMPA or t-BuOK in THF brought about facile migration of SiMe3 group from carbon to oxygen to produce the corresponding silyl ethers in high yields.
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■ An Unusual Product Obtained from the Reaction of Aniline with 1-(2-Chlorocyclopentyl)-piperidine
Jacob Szmuszkovicz, Constance G. Chidester, Lloyd G. Laurian, and Terrence A. Scahill
*Research Laboratories, The Upjohn Company, Kalamazoo, MI 49001, U.S.A.
Abstract
Condensation of aniline with 1-(2-chlorocyclopentyl)-piperidine gave the expected 1-(2-anilinocyclopentyl)-piperidine (1) and an unknown compound. The structure of the unknown compound was shown by x-ray analysis to be 3. Mechanism is proposed for the formation of 3.
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■ Synthesis of 2-Substituted 3(2H)-Isothiazolones from 2-Substituted 5-Aroyl-3(2H)-isothiazolones
Athanase Tsolomitis and Constantine Sandris
*Laboratory of Organic Chemistry, National Technical University, 42 Patission Street, Athene-106 82, Greece
Abstract
2-Substituted 3(2H)-isothiazolones 3 have been prepared from 2-substituted 5-aroyl-3(2H)-isothiazolones 6 , which are readily available from N-substituted 3-aroylpropionamides 5. The nucleophilic displacement on the 5-aroyl group was found t o proceed easily and quantitatively when a benzene solution of compound 6 was stirred at room temperature either with a 10% sodium hydroxide solution or with solid sodium hydroxide.
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■ Unusual cis Stereoselectivity in an Aziridine Cleavage Reaction of Mitomycin C
Gregory L. Verdine, Brian F. McGuinness, Koji Nakanishi, and Maria Tomasz
*Department of Chemistry, Columbia University, 3000 Broadway, Mail Code 3114, New York, New York 10027, U.S.A.
Abstract
Mitomycin C (1) undergoes a stereoselective aziridine ring- opening reaction upon treatment with trifluoroacetic acid in aprotic media to give 1β-hydroxy-2β-trifluoroacetamido-7-aminomitosene (3). Its formation is postulated to involve acid-catalyzed degradation of MC to the intermediate carbocation 7, which captures trifluoroacetate ion predominantly from the β-face at the 1-position to yield trifluoroacetate ester 8. Internal transacylation yields the observed product 3. A high yield synthesis of 3 is presented as well as the implications of this reaction for the occurrence of acidic activation of MC in vivo. The synthetic utility of 3 is also mentioned.
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■ Regio and Stereoselective Rearrangements of Stereoisomeric 7-Oxirylbicyclo[4.2.0]octan-7-ols
Chrong-Shiong Hwang and William Reusch
*Department of Chemistry, Michigan State University, East Lansing, MI 48824, U.S.A.
Abstract
The four racemic diastereomers of the title compound (1a through - 1d) have been prepared by epaxidation of related vinyl cyclobutanols (6 and 7). Each epoxy alcohol is converted to a corresponding halohydrin (9a through 9d) by magnesium bromide, and this transformation is reversed by the action of methanolic base. Mild treatment of the title compounds with boron trifluoride induced regio and stereoselective rearrangement to ringexpanded hydroxymethyl-substituted ketones (2b, 2a and 3a from 1a, 1c and 1d respectively). Isomer 1b did not react. Structural assignments were made on the strength of β-elimination of these ketols to enones 4 and 5, as well as reduction to cis and trans diols 10 and 11.
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■ Synthesis of Heterocycles Using Aminoacetals
James M. Bobbitt and André J. Bourque
*Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060, U.S.A.
Abstract
The use of 2-aminoacetaldehyde acetals as C-C-N synthons in heterocyclic synthesis is summarized. The Pomeranz - Fritsch synthesis of isoquinolines and its modifications since 1970 are described. Coverage of the synthesis of other heterocyclic systems using the acetals is given.