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. 11, 2000
Published online:
■ Access to New Cytotoxic Bisindole Alkaloids by a Modified Borch Reductive Amination Process
Guy Lewin,* Corinne Schaeffer, Reynald Hocquemiller, Edgar Jacoby, Stéphane Léonce, Alain Pierré, and Ghanem Atassi
*Laboratoire de Pharmacognosie, Faculté de Pharmacie, av. J.B. Clément, 92296 Châtenay-Malabry Cedex, France
Abstract
A slight modification of the Borch reductive amination method (delayed addition of NaBH3CN) was applied to an indole aldehyde compound, analog of the natural alkaloid, goniomitine. This reaction led to a series of new cytotoxic bisindole alkaloids with a 1,2,3,4-tetrahydroquinoline bridge.
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■ A Selective Synthesis of Both Enantiomers of a 1-Allyl-β-carboline Using the Same Chiral Auxiliary Derived from L-Proline
Yûji Matsuya, Takashi Itoh, Yasuko Enomoto, and Akio Ohsawa*
*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Abstract
In the study of asymmetric allylation of β-carbolines, reversed stereoselectivity toward a same substrate was observed depending on allylating agents. Based on this finding, the synthesis of both enantiomers of 1-allyl-β-carbolines was accomplished on a practical level of yields and selectivities.
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■ New Syntheses of 2-Alkylthio-4-oxo-3,4-dihydroquinazolines, 2-Alkylthioquinazolines, as well as Their Hetero Analogues
Margit Gruner,* Matthias Rehwald, Katrin Eckert, and Karl Gewald
*Institut of Organic Chemistry, Technical University Dresden, D-01062 Dresden, Germany
Abstract
N-Chloroacetylanthranilic acid ethyl ester reacts with potassium thio-cyanate in the presence of alcohol to give the (4-oxo-3,4-dihydroquinazolin-2-yl-sulfanyl)acetic acid ester (3a). In the presence of water or amines the acetic acid derivative (3b) or the acetamide derivatives (3c,d) are obtained. 2-Amino-4-oxo-3,4-dihydroquinazolines (4) arise if vigorous reaction conditions are employed. Analogously, N-chloroacetyl derivatives of 5-membered heterocycles with ena-minocarbonyl structure (5, 7, 9, 11, 13, 20, 23) react with potassium thiocyanate to yield thieno[2,3-d]-, thieno[3,2-d]-, imidazo[4,5-d]-, pyrrolo[3,2-d]-, and thiazolo[4,5-d]pyrimidines (6, 8, 10, 12, 14, 21, 24). Quinazolines (18, 19) are formed from the reaction of 2-chloroacetylaminoacetophenone (16a) and 2-chloroacetylaminobenzophenone (16b) with potassium thiocyanate and subse-quent treatment of the intermediates with amines.
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■ A Novel Approach to a Precursor of the Carbapenem Antibiotic PS-5 via Aziridine Stereospecific Carbonylation
Paolo Davoli* and Fabio Prati
*Dipartimento di Chimica, Università di Modena e Reggio Emilia, via Campi, 183, I- 41100 Modena, Italy
Abstract
Cobalt carbonyl-catalyzed carbonylative ring expansion of optically pure cis-1-benzyl-3-ethyl-2-hydroxymethylaziridine (5) to trans-β-lactam (8) afforded a key precursor of the carbapenem antibiotic (+)-PS-5. Aziridine (5) was obtained in both enantiomerically pure forms by Amano PS lipase—catalyzed esterification in n-hexane using vinyl acetate as acyl donor. The stereochemical pathway of the carbonylation reaction was proved by configurational assignments through chemical correlation.
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■ Synthesis of 4,5,6,7-Tetrahydroisoxazolo[3,4-c]pyridines and Their Antifungal Activities
Ju Young Jang, Young Ju Lee, and Hyung Jin Kim*
*Department of Applied Chemistry, Chonnam National Unviersity, Kwangju, 500-757, Korea
Abstract
4,5,6,7-Terahydroisoxazolo[3,4-c]pyidine derivatives have been synthesized from the corresponding 4H,6H-pyrano[3,4-c]isoxazoles. They were found to display high antifungal activities against some plant pathogens.
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■ Structural and Conformational Studies of 3,8-Diazabicyclo[3.2.1]octane Derivatives, Selective Agonists of μ-Opioid Receptors
Roberto Artali, Daniela Barlocco, Gabriella Bombieri,* Giorgio Cignarella,* and Fiorella Meneghetti
*Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Viale Abruzzi, 42, 20131-I Milano, Italy
Abstract
Quantum mechanic calculations have been done on a set of 3,8-diazabicyclo[3.2.1]octane derivatives in order to elucidate their electronic structure in relation to the affinity towards the m-opioid receptors. The conformations are compared with morphine, chosen for its μ-affinity and structural rigidity. The X-Ray crystal and molecular structures of 3-p-nitrocinnamyl-8-propionyl-3,8-diazabicyclo[3.2.1]octane (1b) and of two higher homologs 8-n-butyroyl-(1c) and pivaloyl- (1d) have been compared with the theoretical results.
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■ Synthesis of 3-Chloro-2-formylpyrrole Derivatives
Jeremy Robertson,* Nikolai Kuhnert, and Yuekun Zhao
*Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, U.K.
Abstract
Regioselective deprotonation of 3-chloro-1-tosylpyrrole is used to prepare the 2-formyl derivative. Application of this chemistry in a synthesis of the left hand pyrrolo-furan substructure of roseophilin is described.
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■ 3-(2-Benzoylallyl)-4-hydroxy-6-methylpyran-2-ones: Synthesis and Intra- and Intermolecular Nucleophilic Additions
Ulrich Girreser, Dieter Heber,* and Martin Schütt
*Pharmaceutical Institute, Department of Pharmaceutical Chemistry, Christian-Albrechts-University, Gutenbergstr. 76, D-24118 Kiel, Germany
Abstract
The reaction of 4-hydroxy-6-methylpyran-2-one (6) with 1-aryl-2-(dimethylaminomethyl)prop-2-en-1-ones (2) is investigated systematically in order to assess its suitability in carbon-carbon bond for-ming reactions as well as to provide the conditions for subsequent ring closure. Using a base-free medium the reaction affords the title 3-(2-benzoylallyl)-4-hydroxy-6-methylpyran-2-ones (7), whereas in the presence of triethylamine the pyrano[4,3-b]pyranes (8) are formed directly. This result is not necessarily contradictory to the Baldwin rules for ring closure. The structures and the mechanism defined is supported by IR and NMR spectroscopy. The intermolecular addition of further nucleophiles to the enone double bond of 7 yields miscellaneous 3-substituted 2-pyrones (14).
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■ Synthesis of 1-Aryl-1,4,5,6-tetrahydropyrimidines and 1-Aryl-3-substituted 1,4,5,6-Tetrahydropyrimidinium Salts
Liliana R. Orelli, María B. García, and Isabel A. Perillo*
*Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956(1113), Buenos Aires, Argentina
Abstract
A synthetic approach to 1-aryl-1,4,5,6-tetrahydropyrimidines (1) is described, by ring closure of N-aryl-N’-formyl-1,3-propanediamines (5) with trimethylsilyl polyphosphate (PPSE). Quaternization of compounds (1) with methyl (or ethyl) iodide led to the corresponding cyclic amidinium salts (2), while treatment of compound (1a) with 2,4-dinitrochlorobenzene yielded an open chain product resulting from hydrolysis of the salt. An alternative method was employed for the synthesis of 1-aryl-1,4,5,6-tetrahydropyrimidinium salts bearing a branched alkyl or an aryl substituent on N3, not accessible through alkylation. Such compounds were obtained in high yields by dehydrogenation of the corresponding hexahydropyrimidines (3). The scope and limitations of both procedures are discussed.
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■ Three Diels-Alder Type Adducts, Ginsenoynes L, M, and N, from the Roots of Panax ginseng
Kazuhiro Hirakura,* Kou Sugama, Makoto Morita, Kaoru Nakajima, Hiroshi Sasaki, Minoru Okada, and Hajime Sato
*Kampo & Pharmacognosy Laboratory, R & D Division, Tsumura & Co, 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Abstract
Three novel acetylenic compounds named ginsenoynes L, M, and N were isolated from the roots of Panax ginseng. These structures were elucidated by 3- and 2-D NMR spectra and other spectral methods. The ginsenoynes L, M, and N were Diels-Alder type adducts of an acetylenic compound and sesquiterpene.
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■ Synthesis of New Dihydroxy-dioxygenated ortho-[2,x]Cyclophanes
Cristian Simion, Alina Simion, Yoshiharu Mitoma, Satoko Nagashima, Takatoshi Kawaji, Iwao Hashimoto, and Masashi Tashiro*
*Tohwa Institute for Science, Tohwa University, 1-1-1 Chikushigaoka, Minami-ku, Fukuoka 815-8510, Japan
Abstract
The synthesis of title compounds (1a-f) by intramolecular reductive coupling is presented. The reaction is carried out in water solution, in the presence of Zn or Al powder, in basic media.
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■ A Practical Procedure for Preparation of N-(endo-8-(3-Hydroxy)propyl-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (TS-951)
Masaji Suzuki,* Toshie Kaneko, Hiroaki Kamiyama, Yutaka Ohuchi, and Sadakazu Yokomori
*Research Center, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-Cho, Ohmiya, Saitama 330-8530, Japan
Abstract
Effective and convergent process for the preparation of a potent and selective 5-HT4 receptor agonist, the title compound, by reaction of 1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxylic acid (6) with endo-3-amino-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]octane dihydrochloride (20) has been described. Furthermore, this process was developed to pilot plant scale. 1-Isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxylic acid (6) was prepared from 2-aminobenzyl alcohol (12) in 65.6% overall yield and endo-3-amino-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]octane dihydrochloride (20) was prepared from 2,5-dimethoxyfuran (16) in 43.4% overall yield.
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■ Reactions of 1-Hydroxyindoles with p-Toluenesulfonyl Chloride and p-Toluenesulfonic Acid
Masanori Somei,* Fumio Yamada, Aya Goto, Masumi Hayashi, and Masakazu Hasegawa
*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
1-Hydroxyindoles produced novel types of compounds such as 4-substituted indoles and 4H-1,3-dioxolo[4,5-b]indoles upon reaction with p-toluenesulfonyl chloride in acetone. Contrastively, 5-tosyloxyindole and 2H-1,2-oxazino[2,3-a]indole were generated upon reaction with p-toluenesulfonic acid in acetone.
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■ Synthesis of C2 -Symmetrical Chiral Aromatic Diamines by Diastereoselective Addition to Bis(1,3-oxazolidinyl)aromatics with Grignard Reagents
Takayasu Yamauchi, Kimio Higashiyama,* and Shigeru Ohmiya
*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
C2-Symmetrical chiral bis(1,3-oxazolidinyl)aromatics were prepared by the condensation of aromatic dicarbaldehydes (p-benzene, m-benzene, 2,6-pyridine, 2,5-furan and 2,5-thiophene) with (R)-N-2,4,6-trimethoxybenzyl phenylglycinol (1). Bulky bis(1,3-oxazolidinyl)aromatics underwent diastereoselective addition with Grignard reagents to give new classes of C2-symmetrical chiral diaminoaromatics in high yield and diastereoselectivity. The absolute configurations of bulky bis(1,3-oxazolidinyl)aromatics (3) and bis(tert-amino)aromatics (10a) were confirmed by X-Ray spectroscopy.
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■ Biomimetic Aggregates Formed by Heterocyclic Amphiphiles
Juliette Sirieix, Nancy Lauth - de Viguerie, Monique Rivière,* and Armand Lattes
*Laboratoire IMRCP, UMR 5623, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex 04, France
Abstract
This paper describes interesting self-assembling properties of heterocyclic bolaamphiphiles derived from (E)-urocanic acid (3-[1H-imidazolyl-(4)-yl]propenoic acid). The structures of the aggregates obtained in water were studied by transmission electron microscopy. The formation of an elegant biomimetic superstructure was obtained from a bolaamphiphile having two different head-groups: a urocanic moiety and a methyl carboxylate.
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■ The Cleavage of Sulfonylurea Herbicide Rimsulfuron® under Basic Conditions: A Computational Investigation
Roberta Galeazzi,* Cesare Marucchini, Mario Orena,* and Gianni Porzi
*Dipartimento di Scienze dei Materiali e della Terra, Università di Ancona, Via Brecce Bianche, I-60131 Ancona, Italy
Abstract
By treatment at pH 9.5, starting from sulfonylurea (1f) (Rimsulfuron®), the diheteroaryl amine (3) is exclusively obtained, whereas under the same conditions sulfonylureas (1a-e) showed only cleavage of the SO2-NH bond. A reaction mechanism proceeding through a five-membered transition state was strongly suggested by both semiempirical and ab initio molecular orbital calculations.
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■ Radicalic Ethoxycarbonylation of 3-Iodopyridazines: An Efficient Access to Tri- and Tetrasubstituted Pyridazines
Norbert Haider* and Johann Käferböck
*Institute of Pharmaceutical Chemistry, University of Vienna, Währinger Althanstraße 14, A-1090 Vienna, Austria
Abstract
Introduction of ester groups into positions 4 and 5 of 3-iodo-pyridazines (1,2) by redox decomposition of the oxyhydroperoxide of ethyl pyruvate in a sulfuric acid/toluene two-phase system affords trifunctional pyridazine building blocks (3,4a) in a single step.
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■ Synthesis of New N-Alkyl- and N-Acyldioxinophenothiazine and Acridinone Derivatives
Florence Chatel, Sandrine Morel, Gérard Boyer,* and Jean Pierre Galy
*UMR 6009, Laboratoire de Valorisation de la Chimie Fine, case 552, Université Aix-Marseille III, Av. Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Abstract
The synthesis of new substituted dioxino[b]- and [c]phenothiazines or acridinones is reported. N-Arylation of [1,4]benzodioxin-6-amine with organolead or organobismuth reagents gave N-aryl-2,3-dihydro-1,4-benzodioxin-6-amine; subsequent Bernthsen thionation led to phenothiazine ring formation, followed by N-acylation. On the other hand [1,4]benzodioxin-6-amine was first N-alkylated and the resulting alkylamines were N-phenylated before Bernthsen thionation to provide the tetracyclic phenothiazines. Alternative arylation with chlorobenzoic acid followed by cyclization under acidic conditions afforded the dioxinoacridinones, which were successfully alkylated.
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■ Conjugate Addition of Arylmetal Reagents to an α,β-Unsaturated Ketone. Short Syntheses of (-)-Agatharesinol Dimethyl Ether and (-)-Sugiresinol Dimethyl Ether
Keizo Matsuo,* Yuji Ono, Atsutaka Seki, Hiroshi Kuwajima, and Keiji Nishiwaki
*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka, Osaka 577-8502, Japan
Abstract
(-)-Agatharesinol dimethyl ether and (-)-sugiresinol dimethyl ether, derivatives of (-)-agatharesinol and (-)-sugiresinol isolated from Agathis australisand Cryptomeria japonica, respectively were synthesized starting from aprotected D-glyceraldehyde in five steps through 1,4-conjugate addition of arylmetal reagents to an α,β-unsaturated ketone.
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■ A Novel Synthesis of Chiral DBU/DBN-related Molecules for Use in Asymmetric Base Catalysis
Hiyoshizo Kotsuki,* Atsushi Sugino, Hiromitsu Sakai, and Hiroko Yasuoka
*Laboratory of Natural Products Synthesis, Faculty of Science, Kochi University, 2-5-1, Akebono-cho, Kochi 780-8520, Japan
Abstract
The synthesis of sterically hindered chiral DBU/DBN-related molecules (6) from (+)-camphor lactam (1) is described. The value of the products as chiral organic base catalysts is exemplified by their use in asymmetric Michael addition reactions of β-keto ester (7).