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
Edward C. Taylor's Special Issues, Vol. 35, No. 1, 1993
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■ Total Synrhesis of the Amaryllidaceae Alkaloid (±)-Epielwesine. The Importance of Vinylsilane Stereochemistry in Iminium Ion-Vinylsilane Cyclizations
Robert M. Burk and Larry E. Overman*
*Department of Chemistry, University of California, Irvine, Irvine, California 92717, U.S.A.
Abstract
(±)-Epielwesine (9) was prepared in an efficient and completely stereocontrolled fashion in six steps and 28% overall yield from commercially available 3,4-methylenedioxyphenylacetonitrile (15a). The key step is acid promoted cyclization of the (Z)-vinylsilane-iminium cation (13) to construct the cis-3a-arylhexahydroindole (12) in 95% yield. The Z stereochemistry of the vinylsilane is critical to the success of the iminium ion-vinylsilane cyclization, a result that establishes the importance of hyperconjugative electron release from the β-C-Si σ bond in stabilizing the cyclization transition state. A method for the convenient preparation of Δ1-pyrrolines (3,4-dihydro-2H-pyrroles) or Δ1-piperideines (3,4,5,6-tetrahydropyridines) from nitrile precursors is also provided.
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■ The Intermediacy of Sulfate Esters in Sulfuric Acid Catalyzed Acetylation of Carbohydrates
John A. Hyatt* and G. William Tindall
*Research LAboratories, Eastman Chemical Co., Dvision of Eastman Kodak Company, Kingsport, TN 37662, U.S.A.
Abstract
The acetylation of 1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose in excess acetic anhydride/acetic acid/sulfuric acid was shown by kinetic studies and observation of intermediates to proceed via a rapid formation of the corresponding 6-sulfate ester, followed by rate-controlling acetolysis of the sulfate to give glucose pentaacetate product. The same mechanism is proposed, based on kinetic data, for acetylation of the secondary alcohol 1,2,3,6-tetra-O-acetyl-beta-D-glucopyranose.
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■ Regioselective Substitution in Triflyloxypyrimidines and Chloropyrimidines Using Zinc and Tin Reagents
Jessie Sandosham, Kjell Undheim,* and Frode Rise
*Department of Chemistry, University of Oslo, P.O.Box 1033, Blindern, N-0315 Oslo, Norway
Abstract
2,4-Ditriflyloxy-6-methylpyrimidine has been synthesized and its ability to undergo palladium catalyzed coupling with both zinc and tin reagents studied. Similar coupling reactions with 2,4-dichloropyrimidine establish triflyloxypyrimidines as being more reactive than chloropyrimidines. NOE studies were undertaken to determine the position of the substituents. The arylzinc reagents reacted first and preferably in the 4-position of the pyrimidines.
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■ On the Synthesis of Thieno[c]-fused 1,5-Naphthyridine-9-oxides and 5-oxides
Johan Malm, Anna-Britta Hörnfeldt, and Salo Gronowitz*
*Organic Chemistry 1 Chemical Center, University of Lund, P. O. Box 124, SE-221 00, Lund, Sweden
Abstract
Three different methods have been developed for the synthesis of the six isomeric thieno[c]-1,5-naphthyridine-5-oxides and 9-oxides; direct oxidation of the naphthyridines with m-chlorobenzoic acid, Pd(0)-catalyzed coupling between formylthiopheneboronic acids or formyltrialkylstannylthiophenes and o-bromoamino derivatives of pyridine-N-oxides, and coupling between the same type of thiophene derivatives and nitropyridines. The unsymmetrical biaryls so obtained underwent a reductive cyclization when treated with ammoniacal ferrous sulphate. In the latter cases the yield in the coupling reaction was increased when copper(II) oxide was used as a co-reagent. The 13C-nmr spectra of all six thieno[c]naphthyridines are discussed.
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■ Some Alkylation and Reductive Amination Studies of β-Ketomacrolides as Potential Metal Speciation Materials
Shripad V. Kelkar and Steven V. Ley*
*Department of Chemistry, Imperial College of Science, Technology and Medicine, GB-London SW7 2AY, U.K.
Abstract
The β-ketomacrolide (1) was reduced and alkylated with 2-methoxyethoxymethyl chloride to obtain 3. Mono and bis adducts of 1 were obtained by alkylation and reductive amination. These compounds were synthesised for the metal ion binding studies. Compound (12) binds to potassium and cesium ions.
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■ A Simple Technique to Distinguish between CS and C2 Diastereomeric Diols Derived from Chiral Substrates
Michael E. Jung,* Ivan D. Trifunovich, and Adam W. Sledeski
*Department of Chemistry and Biochemistry, University of California, 405 Hilgard Avenue, Los Angels, CA 90024, U.S.A.
Abstract
A new technique which allows one to easily distinguish between a pair of Cs and C2 diastereomeric diols derived from chiral material is described. The method involves inspection of the 13C nmr spectra of the easily prepared Mosher’s ester of each diol which permits the assignment to be made by simply counting the number of resonances observed.
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■ Enantioselective Synthesis of 6-Substituted 5,6-Dihydro-α-pyranones, (+)-Goniothalamin and (-)-Argentilactone
Masayoshi Tsubuki, Kazuo Kanai, and Toshio Honda*
*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
An enantioselective synthesis of (+)-goniothalamin and (-)-argentilactone has been accomplished by employing the Wittig reactions of phosphoranes with the aldehyde (12) generated in situ by Swern oxidation of the alcohol (13) as a key step.
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■ Syntheses of Dihydroisocoumarins, (±)-Hydrangenol and (±)-Phyllodulcin, Utilizing an Annelation Reaction of Enaminones with Ethyl Acetoacetate. Studies on the β-Carbonyl Componuds Connected with the β-Polyketides XIII
Naoki Takeuchi,* Takako Nakano, Kaori Goto, and Seisho Tobinaga
*Showa College of Pharmaceutical Sciences, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Abstract
Naturally occurring dihydroisocoumarins, (±)-hydrangenol (1) and (±)-phyllodulcin (2) were synthesized from the enaminones (3) and (4) by the annelation reactions with ethyl acetoacetate (5).
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■ Inverse [4+1] Cycloadditions of 3-Methyl-2,3-dihydro-1,3-benzothiazole-2-ylidene with 1,2,4,5-Tetrazines
Peter Imming, Andreas Kümmell, and Gunther Seitz*
*Institut für Pharmazeutische Chemie, Philipps-Universität, Marbacher Weg 6, D-35032 Marburg/Lahn, Germany
Abstract
[4+1] Cycloadditions of the nucleophilic singlet carbene 3-methyl-2,3-dihydro-1,3-benzothiazole-2-ylidene (2) with the electron-deficient s-cis-fixed diazadiene systems of a series of substituted 1,2,4,5-tetrazines (4a-c), with CF3, SCH3 and C6H5-groups are described together with some unexpected follow-up reactions.
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■ Rearrangement of Exo-1,4:2,3-diepoxy-1,2,3,4-tetrahydronaphthalene: Formation of a Novel Isochromene via Grob Fragmentation
Larry G. French* and Timothy P. Charlton
*Department of Chemistry, St. Lawrence University, Canton, NY 13617, U.S.A.
Abstract
The suitability of various acid catalysts for effecting the ring contracting rearrangement of an epoxidized benzyne/furan cycloadduct (1b) to α-formyl-2-indanone (7) was investigated. Nafion-H was demonstrated to be an effective catalyst for this transformation. Competing rearrangement pathways were evident under catalysis by acidic alumina and led to the formation of the novel 1H-2-benzopyran-1-carboxaldehyde (9) in addition to the expected product.
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■ Pyrazoloquinazolines from 2-Aminobenzoylhydrazine
Norton P. Peet* and Edward W. Huber
*Marion Merrell Dow Research Institute, 2110 east Galbraith Road, Cincinnati, Ohio, 45215, U.S.A.
Abstract
Brief treatment of 2-aminobenzoylhydrazine (2) with diethyl acetonedicarboxylate in ethanol gave 3-(benzoylhydrazono)pentanedioic acid diethyl ester (3). However, with extended reaction times the product of this condensation was 3-amino-3,4-dihydro-4-oxo-2,2(1H)-quinazolinediacetate (5). In the latter transformation, diethyl 1,3,4,5-tetrahydro-5-oxo-2H-1,3,4-benzotriazepine-2,2-diacetate (6) is an obligatory intermediate. Cyclization of 5 with sodium carbonate in ethanol gave ethyl 2,3,4,9-tetrahydro-2,9-dioxopyrazolo[5,1-b]quinazoline-3a(1H)-acetate (8), and methylation of 8 afforded its 1-methyl derivative (9).
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■ Distinct Solvent-Dependence in the Photoreactions of Purine Nucleosides with Pyrimido[5,4-g]pteridinetetrone N-Oxide: Possible Generatiion of Hydroxyl Radical from the Excited N-Oxide in Alcohols
Yoshifumi Maki,* Toru Makino, Kosaku Hirota, and Magoichi Sako*
*Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
Photoreaction of 2’,3’,5’-tri-O-acetyladenosine (5) with pyrimido[5,4-g]pteridinetetrone N-oxide (1) in acetonitrile gave N6-cyanomethyl-2’,3’,5’-tri-O-acetyladenosine (6) as a major detectable product via coupling of adenosyl radical with cyanomethyl radical generated by the mediation of 1. Under the analogous conditions, N2-benzoyl-2’,3’,5’-tri-O-acetylguanosine (8) underwent oxidative degradation of the guanine skeleton by 1. In sharp contrast, photoreactions of 5 and 8 with 1 in tert-butanol resulted in the formation of the corresponding 8-hydroxypurine nucleosides (7) and (9), respectively. These facts and other observations suggest that 1 could generate hydroxyl radical upon irradiation in alcohols.
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■ Synthesis of a Cephalosporin-Doxorubicin Antitumor Prodrug: A Substrate for an Antibody-targeted Enzyme
Louis N. Jungheim,* Timothy A. Shepherd, and James K. Kling
*Lilly Reserach Laboratories, Eli Lilly & Company, Indianapolis, IN 46285-4813, U.S.A.
Abstract
Cephalosporin (12) substituted at the C-3’ position with the potent oncolytic agent doxorubicin (2) was synthesized as a potential prodrug for the treatment of solid tumors. We envision the conversion of prodrug to free doxorubicin to be mediated by an immunoconjugate, consisting of a β-lactamase enzyme which is covalently attached to a monoclonal antibody, which has been prelocalized on the tumor cell surface. Doxorubicin was covalently attached to the cephalosporin nucleus via a carbamate linkage. This was accomplished by condensation of the amino sugar moiety of doxorubicin with cephem 3’-p-nitrophenyl carbonate (10).
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■ The Use of o-Nitroarylacetonitriles in the Mitsunobu Reaction: Mechanistic Implications and Synthetic Applications
John E. Macor* and Jennifer M. Wehner
*Department of Medical Chemistry, Central Research Division, Pfizer Inc., Groton, Connecticut 06355, U.S.A.
Abstract
o-Nitroarylacetonitriles (1) have been used as carbon acid participants in the Mitsunobu reaction to yield 2-(o-nitroaryl)-2-alkylacetonitriles (2). Reductive cyclization of 2 afforded 3-alkylindoles (3) in moderate yield. The use of o-nitroarylacetonitriles (1) as acid/base indicators and mechanistic probes in the Mitsunobu reaction in conjunction with results from other studies have led to the following hypotheses concerning the mechanism of that reaction: 1) the nature of the acid participant in a Mitsunobu reaction determines the mechanistic course of the reaction; and 2) carbon acid participants react via an “outer sphere” second order process whose rate is heavily dependent on the nature of the alcohol used; 3) heteroatom acid participants (i.e. -OH and -NH-) having high affinity for phosphorus utilize an “inner sphere” first order process which does not depend heavily on the nature of the alcohol used; and 4) the order of reactant addition can have significant effects on the reaction rate and success, and optimal reaction results occur with the addition of the alcohol last to a solution of DEAD/Ph3P/acid participant.
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■ Rhodium(II) Catalyzed Cyclization of Diazo Thiocarbonyl Compounds for Heterocyclic Synthesis
Albert Padwa,* Frederic R. Kinder, William R. Nadler, and Lin Zhi
*Department of Chemistry, Emory University, 1521 Pierce Drive Atlanta, Georgia 30322, U.S.A.
Abstract
The mesoionic thioisomünchnone system was prepared from the rhodium(II) acetate catalyzed cyclization of a diazothioamide and was found to undergo smooth 1,3-dipolar cycloaddition with N-phenylmaleimide. In contrast to this system, the rhodium(II) reaction of an α-diazo-β-oxo ester containing a thiocarbonyl group produced a cyclic thiocarbonyl ylide which extruded sulfur from a transient episulfide intermediate.
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■ Synthesis of Ether Analogues of (±)-Acetomycin
Huw M. L. Davies* and Baihua Hu
*Department of Chemistry, Wake Forest University, Box 7486, Winston-Salem, North Carolina 27109, U.S.A.
Abstract
Short syntheses of (±)-2a-c, ether analogues of acetomycin (1a) are described. The approach is based on a novel entry to furanones by rearrangement of tert-butyl 1-vinylcyclopropane-1-carboxylates. The cyclopropanes are stereoselectively formed by the rhodium(II) catalyzed decomposition of vinyldiazomethanes in the presence of vinyl ethers.
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■ Benzidine Type Electron Donors Fused with 1,2,5-Chalcogenadiazole Units
Takanori Suzuki, Tsuneyuki Okubo, Akihisa Okada, Yoshiro Yamashita, and Tsutomu Miyashi*
*Department of Chemistry, Faculty of Science, Tohoku University, Aoba-ku, Ssendai 980-8578, Japan
Abstract
The title electron donors (1 and 2) were prepared from 4-bromo-7-diakylaminobenzo[c][1,2,5]thiadiazole (3). They are electrochemically amphoteric, and the absorption maxima in the 500-550 nm region were assigned to the intramolecular charge-transfer (CT) bands. The X-ray analyses of 1b and 1b+·PF6- revealed that the twisted geometry of 1b became planar upon one-electron oxidation, and a coplanar “ribbon”-like network was formed by S···N interactions in the crystal of 1b+·PF6-.
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■ Five Phenolic Compounds in the Underground Parts of Vancouveria hexandra
Munekazu Iinuma,* Yoko Kanie, Toshiyuki Tanaka, Mizuo Mizuno, and Frank A. Lang
*Department of Pharmacognosy, Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
From the underground parts of Vancouveira hexanda, a new 2-phenoxybenzochromone and four new prenylated flavones were isolated. Their structures were determined by the spectral analysis.
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■ Reaction of Diazole Anions with Hexafluorobenzene: An Unexpectedly Facile Entry into Hexa(diazol-1-yl)benzenes
Robert N. Henrie II* and Walter H. Yeager
*FMC Corporation, Agricultural Chemical Group, P.O. Box 8, Princeton, New Jersey 08543, U.S.A.
Abstract
Diazole anions react with hexafluorobenzene to give hexa(diazol-1-yl)benzenes in excellent yield, even with unfavorable reaction stoichiometries. In contrast, pyrrole anions give predominantly or exclusively 1,4-disubstituted products. This novel hexasubstitution reaction is discussed in terms of an SRN1 mechanism.
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■ A Facile and Efficient Entry to Naphtho[2,3-g]indole-6,11-dione Derivatives
Pedro Molina,* Alberto Tárraga, Alicia Ferao, and Carmen Gaspar
*Departamento de Química Orgánica, Facultad de Química, Universidad de Murcia, Campus de Espinardo, E-30071, Murcia, Spain
Abstract
Condensation of anthraquinone-2-carboxaldehyde with several α-azido carbonyl compounds leads to α-azido-β-antraquinonyl acrylates which under heating undergo ring-closure to give naphtho[2,3-g]indole-6,11-diones in a completely regioselective fashion.
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■ Preparation of Sterically More Crowded 1,5-Disubstituted Imidazoles by the Regioselective N-Alkylation
Choji Kashima, Yukari Harada, and Akira Hosomi
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
4-Substituted 1-acetylimidazoles (6), which were derived from 4(5)-substituted imidazoles (1), were N-alkylated by the treatment with alkyl halides. During the work-up, the resulting N-alkylated products were easily hydrolyzed into 1,5-disubstituted imidazoles (3). These reactions were regarded to be the general method for the preparation of sterically more crowded 1,5-disubstituted imidazoles (3).
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■ The New Appraoch to Antibiotic Carbazomycins. The Formal Total Synthesis of Carbazomycin A and B
Satoshi Hibino,* Akiko Tonari, Tominari Choshi, and Eiichi Sugino
*Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-02, Japan
Abstract
Deoxycarbazomycin B has been synthesized in a four step sequence. The key reaction has been the thermal electrocyclic reaction of 1,3,5-hexatriene system involving the indole 2,3-bond.
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■ Spiro 1,3,4,6-Tetrathiapentalene-2-thiones
Jan Becher,* Ole Simonsen, Helle Sæycher, Thomas Kruse Hansen, Tine Jørgensen, and Søren Bøwadt
*Department of Chemistry, Odense University, Campusvej 55 DK-5230 Odense M., Denmark
Abstract
Reaction of the geminal α,α-dichloroketones (3) and (5) with the 4,5-dimercapto-1,3-dithiole-2-thionedianion (2) yields the spiro 1,3,4,6-tetrathiapentalene-2-thiones ( 4) and (6). The structure of 1,3,4,6-tetrathiapentalene-2-thione-5-spiro-3’-benzo[c]furan-1’-(3H)-one (4) was determined by X-ray crystallography.
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■ Prepararion of 2-Amino-4H-pyrazolo[1,5-a]indole Derivatives by Boulton-Katritzky Rarrangement
Hajime Katayama,* Noriyuki Takatsu, Masahiko Sakuarada, and Yusuke Kawada
*Niigata College of Pharmacy, 5-13-2 Kamishin'ei-cho, Niigata 950-2081, Japan
Abstract
2-Benzoylamino-3,3a-dihydro-4H-pyrazolo[1,5-a]indole was prepared by extended type-2 Boulton-Katritzky rearrangement and transferred into 2-amino-4H-pyrazolo[1,5-a]indole.
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■ Chimistry on the Damage and Repair of Thymine and Thymidine Derivatibes
Reiko Yanada, Takashi Harayama, and Fumio Yoneda*
*Faculty of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
This review describes on the oxidative damage and repair studies of nucleic acids, particularly of thymine and thymidine derivatives.
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■ Heterocyclic Rearrangements of Benzofuroxans and Related Compounds
Alan R. Katritzky* and Mikhail F. Gordeev
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.
Abstract
Heterocyclic rearrangements of benzofuroxans, benzotriazoles, furoxans, 1,2,4-oxadiazoles, benzofuroxans, anthranils, triazoles, benzotriazoles, isoxazoles and some related compounds are reviewed in connection with the problem of benzofuroxan ring chain tautomerism. Both mono- and bicyclic rearrangements of these five-membered heterocycles and their benzo-derivatives, and related heterocyclic transformations are discussed with an emphasis on the most relevant earlier and recent studies.
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■ Recent Advances in the Chemistry of Condensed Pyridazines: Synthesis of Bi- and Tricyclic Systems by Annelation of Five-, Six-, and Seven-membered Rings to a Preformed 1,2-Diazine Nucleus
Norbert Haider and Gottfried Heinisch*
*Institut für Organische und Pharmazeutisch Chemie, Universität Innsbruck, Innrain 52, A-6020 Innsbruck, Austria
Abstract
Methods for the preparation of a wide variety of pyridazine-containing bi- and tricyclic ring systems, starting from appropriately substituted pyridazines are reviewed. The compilation comprises pyridazine-fused five-, six-, and seven-membered carbo- and heterocyclic systems. Particular interest is focused on compounds bearing no additional substituents in the 1,2-diazine moiety. In the syntheses discussed, diaroylpyridazines, aroylpyridazinecarboxylic acids, alkylpyridazinecarboxylic acids, aminopyridazinyl aryl ketones, and chloro- or alkylpyridazinecarbonitriles represent the key intermediates.
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■ The Synthesis of Pyridines, Quinolines and Other Related Systems by the Vilsmeier and the Reverse Vilsmeier Method
Otto Meth-Cohn*
*Chemistry Department, Sunderland University, Sunderland SR1 3SD, U.K.
Abstract
Quinolines, pyridines, thienopyridines, quinolones, isoquinolones, naphthyridines and related systems can be made efficiently from acylamides under Vilsmeier conditions. This review focusses on the application of both the Vilsmeier and the Reverse Vilsmeier approach. In the former method the acylamide becomes a nucleophile and is the source of the nitrogen and the 2,3-carbons of the resulting heterocycle while in the latter the acylamide reacts as an electrophile which yields the product heterocycle by reaction with an electron-rich alkene or its equivalent. This ‘alkene’ can be an enamine, a vinyl ester, an amide, or a masked nucleophilic alkene such as a ketone or an ‘active’ methyl or methylene group as in an α-substituted acetic acid.