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. 41, No. 2, 1995
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■ Cycloaddition Reactions of 7-Substituted Acenaphtho[1,2-d]pyrazolo[1,2-a]benzotriazoles with Dimethyl Acetylenedicarboxylate
Otohiko Tsuge*, Taizo Hatta, Masafumi Sugaya, Eiji Yunoki, Hidenori Gau, and Akikazu Kakehi
*Department of Industrial Chemistry, Kumamoto Institute of Technology, 4-22-1, Ikeda, Kumamoto 860, Japan
Abstract
The reactions of the title 7-phenyl- and 7-methylacenaphthopyrazolobenzotriazoles (triazapentalenes) with dimethyl acetylenedicarboxylate gave a mixture of the corresponding initial azomethine imidic cycloadduct and its isomeric pyrazinopyrimidine, whose yields greatly depended on the reaction conditions. Structures of both the initial and isomeric products were determined by X-ray crystallographic analyses. The initial cycloadduct readily isomerized to the pyrazinopyrimidine. It has been found that the methyl-substituted pyrazinopyrimidine underwent the Michael-type addition reaction.
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■ Regiospecific Synthesis of N-Alkyl-4- and 5-Substituted Imidazoles
Gideon Shapiro* and Berta Gomez-Lor
*Preclinical Research, Sandoz Pharma Ltd., CH-4002 Basel, Switzerland
Abstract
A facile regiospecific synthesis of 4- and 5-substituted N-alkyl imidazoles has been developed from N-trimethylsilyloxyethylimidazole(s). The method combines directed metallation with alkyl triflate mediated imidazole quaternization and SEM group cleavage.
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■ Unexpected Iodine Catalyzed Cyclization for Synthesis of 2,2-Dialkyl-2,3-dihydrobenzofurans
Kyoung Mahn Kim and Eung K. Ryu*
*Korea Research Institute of Chemical Technology, P. O. Box 107, Yusong, Taejon 305-606, Korea
Abstract
2-(β-Methylallyl)phenol and 2-isobutenylphenol derivatives were easily cyclized to 2,2-dimethyl-2,3-dihydrobenzofurans in the presence of a catalytic amount of iodine without any formation of iodinated products.
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■ Diene-transmissive Diels-Alder Reaction of 2-Vinyl-1-oxabutadiene System
Otohiko Tsuge*, Taizo Hatta, Hideki Yoshitomi, Katsumi Kurosaka, Toshitsugu Fujiwara, Hironori Maeda, and Akikazu Kakehi
*Department of Industrial Chemistry, Kumamoto Institute of Technology, 4-22-1, Ikeda, Kumamoto 860, Japan
Abstract
The first example for the diene-transmissive Diels-Alder reaction of 2-vinyl-1-oxabutadiene system is presented by the reactions of 1,5-diphenyl- and 1,5-di(2-thienyl)-1,4-pentadien-3-ones with electron-rich enamines as the first dienophiles and then with electron-deficient dienophiles as the second.
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■ Isolation and Structural Elucidation of Bioactive C-12,15-cis Non-adjacent Bis-THF Annonaceous Acetogenins
Zhe-Ming Gu, Lu Zeng, and Jerry L. McLaughlin*
*Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, U.S.A.
Abstract
In further investigation on the EtOH extract of the bark of Annona bullata, two novel Annonaceous acetogenins, C-12,15-cis-bullatanocin (1) and C-12,15-cis-bullatalicin (2), were successfully separated by hplc from fractions in which they were mixed with bullatanocin (7) and bullatalicin (8), their respective C-12/15-trans diastereomers. Their relative stereochemistries between the two THF rings were determined through preparations of their respective 16,19-formaldehyde acetal derivatives (1a and 2a). The absolute configurations of 1 and 2 were resolved by analyses of the 1H nmr data of the (S)- and (R)-Mosher ester derivatives (1b,1c and 2b,2c) of 1a and 2a. Compounds (1) and (2) are the first examples of C-12/15-cis non-adjacent bis-THF Annonaceous acetogenins and showed potent bioactivities, comparable to those of 7 and 8, with notable cytotoxic selectivities among six human solid tumor cell lines.
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■ Synthesis of New Armed Cyclopolyamines and Their Selective Extraction Properties for Metal Ions
Kiyoshi Matsumoto*, Keisuke Fukuyama, Hirokazu Iida, Mitsuo Toda, and J. William Lown
*Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, 606-01, Japan
Abstract
A variety of new armed cyclopolyamines were prepared by high pressure SNAr reactions (0.8 GPa, 100°C) of cyclopolyamines with heteroaromatic halides. Certain of these agents show selective extraction properties for Hg2+ and Ag+ ions.
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■ A Synthesis of Optically Active Platyphyllide. Determination of Its Absolute Configuration
Shigeru Nagashima, Hitomi Ontsuka, Motoo Shiro, and Ken Kanematsu*
*Institute of Synthetic Organic Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University 62, Higashi-ku, Fukuoka 812, Japan
Abstract
The first enantioselective total synthesis of platyphyllide (1), based on the allenyl ether intramolecular cycloaddition strategy, is described, revealing the absolute configuration of this compound.
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■ Synthesis and 1H Nmr Complexation Study of a Novel Macrocyclic Polyether Containing 1,1'-Biazulene Unit
Der-Seang Lee, Paw-Wang Yang, Tadayoshi Morita*, and Tetsuo Nozoe
*Department of Chemistry, Tohoku University, Aoba-ku, Sendai 980-77, Japan
Abstract
A new class of chiral macrocyclic polyethers containing 1,1’-biazulene unit was prepared from the reaction of 2,2’-dihydroxy-3,3’-bis(methoxycarbonyl)-1,1’-biazulene with tetra- or pentaethyleneglycol ditosylate by a high dilution technique. Complexation study with alkali metals by 1H nmr indicated ion selectivity for these macrocycles. The crystal structure was studied by X-ray diffraction.
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■ A Synthesis of 6-Methylindole Derivatives by Methylthiomethylation at 6-Position in Indole Nucleus
Satoshi Hirano, Ritsuko Akai, Yoshihiko Shinoda, and Shin-ichi Nakatsuka*
*Faculty of Agriculture, Gifu University, Yanagido, Gifu 501-11, Japan
Abstract
6-Methylindole derivatives were synthesized by introduction of methylthiomethyl group onto the 6-position of indole nucleus and subsequent desulfurization.
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■ Synthesis of 6-Fluoroquinolones Substituted at C-7 by 1'-Demethyllincomycin and by Dihydroconessimine
Sandrine Deloisy, Alain Olesker*, and Gabor Lukacs
*Institut de Chimie des Substances Naturelles, C.N.R.S., 91198 Gif sur Yvette, France
Abstract
The boron-chelated carboxylic acid of 6,7-difluoroquinolone (8) was substituted at C-7 by the 2,3,4,7-tetra-O-acetate of 1’-demethyllincomycin (4) and by dihydroconessimine (14). The resulting dechelated products did not reveal any antibacterial activity. A new efficient procedure for the preparation of the 2,3,4,7-tetra-O-acetate of 1’-demethyllincomycin (4) is proposed.
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■ Hypotensive Constituents from the Bark of Holarrhena pubescens (Holarrhena antidysenterica)
Bina Shaheen Siddiqui*, Shahid Bader Usmani, Sabira Begum, Salimuzzaman Siddiqui, Khalid Aftab, and Anwar-ul-Hassan Gilani
*H. E. J. Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
Two new alkaloids of conanine series, holamide (N-(N’-methylacetamido)-3-oxo-1,4-conadiene) (1), pubescinine (11α-acetoxy-N-demethyl-3-oxo-1,4,17(20)-conatriene) (2) and a known alkaloid norconessine (3-N-methylamino-5-conanene) (3), have been isolated from the bark of Holarrhena pubescens Buch. Ham (Holarrhena antidysenterica Linn.) (Apocynacea). Their structures have been established through spectroscopic studies. Both 1 and 2 showed hypotensive activity in rats at a does of 3 mg/kg.
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■ A Synthesis of the Polyhydroxylated Pyrrolidines : Synthesis of 1,4-Dideoxy-1,4-imino-D-lyxitol and N-Benzyl-4-epi-(-)-Anisomycin
Shi Zhi-cai, Zeng Chun-min, and Lin Guo-qiang*
*Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Abstract
A synthesis of 1,4-dideoxy-1,4-imino-D-lyxitol and N-benzyl-4-epi-(-)-anisomycin was described.
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■ Reaction of Pentachloropyridine with α-Lithiated Arylacetonitriles and Methyllithium in Ether
Edward R. Biehl*, Hala Mohammed Refat, and Amamed A. Fadda
*Department of Chemistry, Southern Methodist University, Dallas, TX 75275, U.S.A.
Abstract
Ether slurries of α-lithioarylacetonitriles (3) when added to ether solutions of 2,3,5,6-tetrachloro-4-pyridyllithium (2) at -70°C give clear, red solutions upon warming to -20°C. Further warming to room temperature, produces bright scarlet precipitates which upon proton quench provide α-aryl-2,3,5,6-tetrachloro-4-pyridylacetonitriles (4) in excellent yields (98-80%). A mechanism is proposed in which the key step involves a lithium-chlorine exchange between 2 and α-lithio-α-chloroarylacetonitriles (7). Experimental evidence for the intermediacy of 7 in these reactions is presented.
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■ Synthesis and Structure Assignment of 1-[(2-Hydroxyethoxy)methyl]- and 1-[(1,3-Dihydroxy-2-propoxy)methyl]-6-azaisocytosine
Long-Chih Hwang, Chyi-Jia Wang, Gene-Hsiang Lee, Yu Wang, and Cherng-Chyi Tzeng*
*School of Chemistry, Kaohsiung Medical College, Kaohsiung City 807, Taiwan, R.O.C.
Abstract
1-[(2-Acetoxyethoxy)methyl]-6-azaisocytosine and 1-[(1,3-dibenzyloxy-2-propoxy)methyl]-6-azaisocytosine have been prepared, and their unambiguous assignment of 1H and 13C peaks through the 1H-13C heteronuclear correlation (HETCOR) nmr experiments is described. The X-ray crystallographic analysis reveals unambiguously the site of glycosylation at N1. Deprotection of both acyclonucleosides provided 1-[(2-hydroxyethoxy)methyl]-6-azaisocytosine and 1-[(1,3-dihydroxy-2-propoxy)methyl]-6-azaisocytosine, respectively.
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■ Synthesis of Triazolidine-1,3,5,7-tetraone and Pyrimidin[1,5]diazepine Derivatives by Carbon Suboxide
Leonardo Bonsignore* , Filippo Cottiglia, Giuseppe Loy, and Daniela Secci
*Dipartimento Farmaco Chimico Tecnologico, Università di Cagliari, Via Ospedale 72, I-09124, Cagliari, Italy
Abstract
A one step synthesis of 6H-pyrazolidin[1,2-a][1,2,4]triazolidine-1,3,5,7-tetraones and pyrimidino[1,5]diaza- and thiazepines by carbon suboxide is here described.
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■ Regiocontrolled Syntheses of Benzo[b]quinolizinium and Heteroisoquinolinium Cations
William G. Earley*, John A. Dority Jr., Virendra Kumar, and John P. Mallamo
*Sterling Winthrop Pharmaceuticals Research Division, Department of Medicinal Chemistry, 1250 S. Collegeville Rd., Collegeville, PA 19426-0900, U.S.A.
Abstract
A regiocontrolled synthesis of 10-alkoxy and alkyl substituted benzo[b]quinolizinium salts is described. Synthesis of a novel 9-alkoxythiazolo[3,2-b]isoquinolinium cation is reported. In addition the synthesis of several new N-alkylimidazo[1,2-b]isoquinolin-4-ium cations is described. Condensation of dianions (1) with heteroaromatic aldehydes and ketones provides diols in 35-85% yield. Cyclization of diols (2) with POCl3 gives previously unreported 10-substituted benzo[b]quinolizinium cations and heteroisoquinolinium cations (3) in 35-90% yield.
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■ Effect of Fluorine-Substitution on Basicity of Benzo[h]quinoline, Benzo[f]quinoline and Quinoline
Wei Wu, Ken-ichi Saeki, and Yutaka Kawazoe*
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabedori, Mizuho-ku, Nagoya 467, Japan
Abstract
The effect of fluorine-substitution on the acid-dissociation constant was examined using 19 types of mono- and difluorinated derivatives of benzo[h]quinoline, benzo[f]quinoline and quinoline. Decrease in pKa were induced by fluorine substitution and were dependent on the number of bonds between the substituent F atom and the basic N atom, whereas pKa-increases were induced by a substituent F atom spatially interacting with the basic N atom. The spatial interaction between F and N was analyzed by means of a semiempirical molecular orbital method MOPAC PM3.
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■ An Improved Procedure for the Preparation of Aromatic Heterocyclic N-Oxides
Soo Young Rhie and Eung K. Ryu*
*Korea Research Institute of Chemical Technology, P. O. Box 107, Yusong, Taejon 305-606, Korea
Abstract
An improved procedure for the preparation of aromatic heterocyclic N-oxides is described. Nitrogen containing heterocyclic compounds gave their N-oxides in excellent yields by the reaction of m-CPBA in DMF/MeOH in the presence of HF in a short time under mild reaction conditions. The presence of HF and MeOH is crucial for the reaction.
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■ Thermal Reaction of 1,2,4-Triazolium N-Allylides: Formation of Mesomeric Betaines, 1,2,4-Triazolo[4,3-a]pyridiniumides, via Back-donated 1,6-Cyclization
Yoshiro Matsuda*, Yasushige Chiyomaru, Chieko Motokawa, and Takanobu Nishiyori
*School of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852, Japan
Abstract
The reaction of 1,2,4-triazolium salt (7) with polarized olefins (2, 3a,b) in the presence of K2CO3 in CHCl3-EtOH gave the corresponding triazolium N-allylides (8a-c). Thermolyses of the N-allylides (8a,c) afforded the mesomeric betaine (9a) and the 8-amino-1,4-triazolo[4,3-a]pyridine derivative (10). Similar treatment of the salt (7) with polarized olefins (3c,d, 4a) directly yielded mesomeric betaines (9c-e), while the reaction of the salt (7) with polarized olefin (4b) gave the pyrrolo[1,2-d]-1,2,4-triazine derivative (11). The formation of mesomeric betaines is suggested to proceed via back-donated 1,6-cyclization.
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■ Synthesis of a Novel N-Methoxymethylpyrrole-containing DNA Minor Groove Binding Oligopeptide Related to Distamycin
Rulin Zhao and J. William Lown*
*Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
Abstract
A novel N-methoxymethylpyrrole-containing DNA minor groove binding oligo-peptide designed for increased solubility and enhanced cellular uptake and related to distamycin has been synthesized.
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■ Synthesis of 4-Hydroxy-1-methylbenzimidazole and 7-Hydroxy-1-methylbenzimidazole
Alan R. Katritzky*, Richard P. Musgrave, Bogumila Rachwal, and Chris Zaklika
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, U.S.A.
Abstract
4-Hydroxy-1-methylbenzimidazole (1) was synthesised via condensation of 2-amino-3-nitrophenol (3) with trimethyl orthoformate, reduction of the resulting 4-nitrobenzoxazole (4) to amine (5), reaction with hydroxymethylbenzotriazole to form benzotriazolyl adduct (6), reduction to give 4-methylaminobenzoxazole (7), and finally base catalyzed rearrangement. The synthesis of 7-hydroxy-1-methylbenzimidazole (2) was accomplished by reduction of 4 with sodium borohydride to form 3-nitro-2-methylaminophenol (8), followed by hydrogenation to give amino derivative (9) and condensation with trimethyl orthoformate.
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■ Transformation of Na-Boc-tetrahydroalstonine to Na-Boc-5β-cyanotetrahydroalstonine, Na-Boc-21α-cyanotetrahydroalstonine, and Na-Boc-3,14-didehydrotetrahydroalstonine
Minna Halonen, Reija Jokela, and Mauri Lounasmaa*
*Laboratory for Organic and Bioorganic Chemistry, Technical University of Helsinki, FIN-02150 Espoo, Finland
Abstract
Tetrahydroalstonine (1) was transformed to its Na-Boc-derivative (4), which was then oxidized to the corresponding cis-Nb-oxide (5a). The modified Polonovski reaction of the cis-Nb-oxide (5a), followed by KCN treatment, led to Na-Boc-5β-cyanotetrahydroalstonine (7), Na-Boc-21α-cyanotetrahydroalstonine (8a), and Na-Boc-3,14-didehydrotetrahydroalstonine (9), of which the first (7) is a good model for the naturally occurring 5β-carboxytetrahydroalstonine (2b) and the second (8a) the chemical equivalent of Na-Boc-20,21-didehydro-tetrahydroalstonine (Na-Boc-cathenamine) (8b).
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■ A Facile Synthesis of 6-Amino-1-benzyl-4-methyl- and 6-Amino-1,4-dimethylhexahydro-1H-1,4-diazepines, the Amine Part of Substituted Benzamides with a Potent Serotonin 3 Receptor Antagonistic Activity
Hiroshi Harada, Yoshimi Hirokawa, Toshiya Morie, and Shiro Kato*
*Exploratory Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Enoki 33-94, Suita, Osaka 564, Japan
Abstract
A facile synthesis of 6-amino-1-benzyl-4-methyl- and 6-amino-1,4-dimethylhexahydro-1H-1,4-diazepines (16a and 16b) which have been served as the amine part of the new and novel benzamides (3 and 4) with a potent serotonin 3 receptor antagonistic activity is reported. The formation of 1,4-diazepine ring system was achieved by the reaction of tris(hydroxymethyl)nitromethane (11) with N,N’-disubstituted ethylenediamines (12a and 12b). The dehydroxymethylation of the resultant 6-hydroxymethyl-6-nitro-1,4-diazepines (13a and 13b) and successive reduction gave the target compounds (16a and 16b), in approximately 15-30% overall yield.