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
Teruaki Mukaiyama's Special Issues, Vol. 52, No. 1, 2000
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■ Direct Arylation of 2-Pyridones; Photostimulated SRN1 Reaction between Cesium Phenoxides and Chloro-2-pyridones
Hiroyuki Higuchi, Masayo Hattori, and Shigeru Ohmiya*
*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
4-Hydroxyphenyl- (3 and 4) and 6-hydroxyphenyl-1-methyl-2-pyridones (6 and 7) were obtained by the photostimulated reaction of 4-chloro- (1) and 6-chloro-1-methyl-2-pyridone (5), respectively, with variously substituted cesium phenoxides (2). The reactions were proposed to proceed via an SRN1 mechanism.
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■ Application of Oxidative Desymmetrization of meso-Tetrahydrofurans: Syntheses of Functionalized Chiral Building Blocks and of (-)-Alloyohimbane
Akio Miyafuji, Katsuji Ito, and Tsutomu Katsuki*
*Department of Molecular Chemistry, Graduate School of Science, Kyushu University 33, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Abstract
Oxidative desymmetrization of oxygen functionalized meso-tetrahydrofurans was successfully achieved (up to 87% ee) through (salen)manganese(III) catalyzed enantiotopic selective C-H oxidation. The enantioselective synthesis of (-)-alloyohimbane (12) has also been achieved in a short step by using oxidative desymmetrization of meso-tetrahydrofuran as the key step.
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■ Quinoxalines, Benzodiazepines and Benzodiazocines Fused to Pyrrole and Isoindole via N-Acyliminium Ion Aromatic Cyclization
Mohamed Othman, Pascal Pigeon, Pierre Netchitaïlo, Adam Daïch, and Bernard Decroix*
*Laboratoire de Chimie, Faculté des Sciences et Techniques de l'Université du Havre, 25 rue Philippe Lebon, BP 540, 76600 Le Havre, France
Abstract
Quinoxaline (6a), [1,4]benzodiazepines (6b,c) and [2,5]-benzodiazocine (6d) were synthesized from hydroxylactams (3a-d) or (4a-d) via an N-acyliminium ion-pyrrole cyclization reaction. 3 and 4 were prepared in two steps from ready available substituted anilines (la,b) or benzylamines (lc,d).
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■ Cyanocarbonylation of Amines with 5-Tosyloxyimino-2,2-dimethyl-1,3-dioxane-4,6-dione
Nobuya Katagiri,* Minoru Ishikura, Yoshihiro Morishita, and Masahiko Yamaguchi
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
5-Tosyloxyimino-2,2-dimethyl- 1 ,3-dioxane-4,6-dione (3), prepared by the reaction of 5-hydroxyimino-2,2-dimethyl-1,3-dioxane-4,6-dione sodium salt (2) with tosyl chloride, was treated with various amines (4a-c and 6a,b) in the presence of triethylamine to give the corresponding N-cyanocarbonyl derivatives (5a-c and 7a,b). However, reaction of 3 with benzyl alcohol gave rise to the formation of dibenzyl carbonate (10).
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■ A Theoretical Study of the 1,2,3-Triazoloiminodiazomethane Isomerism in the Gas Phase
Rostislav E. Trifonov,* Ibon Alkorta, Vladimir A. Ostrovskii, and José Elguero
*Instituto de Química Médica, CSIC, Juan de Cierva 3, E-28006 Madrid, Spain
Abstract
The ring opening reactions of the 1,2,3-triazolate anion, of the three tautorners of NH-1,2,3-triazole, and of different 1,2,3-triazolium cations, to give the corresponding iminodiazomethanes, have been studied by means of ab initio calculations at the HF/6-31 ** level. The 1,5-electrocyclization reactions of 1,2,3-triazolate and 1H-1,2,3-triazole proceed through planar transition states with high and medium energy barriers, respectively. In both cases the cyclic forms are thermodynamically more stable than the open-ring ones. In contrast, the decomposition of the 1,2-H-1,2,3-triazolium cation into protonated iminodiazo-methane is an exothermic process. In the last case, the preferable way of the reaction proceeds via non-aromatic intermediates (1,4H2- and 1,1H2-1,2,3-triazolium ions) which have a very low activation energy towards the ring opening. It has been found that there is a high ππ-conjugation between diazornethyl and imine fragments in the chain forms.
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■ A Convenient Synthesis of New 1-Alkynyl-1H-benzotriazoles by Reaction of Alkynyl(phenyl)iodonium Salts with Benzotriazole Ion
Tsugio Kitamura,* Norihiko Tashi, Kuniyuki Tsuda, Haiying Chen, and Yuzo Fujiwara*
*Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Abstract
The reaction of arylethynyl(phenyl)iodonium tosylates with benzotriazole ion gave new 1-alkynyl-1H-benzotriazoles in good yields. This result indicates that alkynyliodonium salts can be used for direct alkynylation of benzotriazole. However, the similar reactions of (tert-butylethynyl)(phenyl)iodonium and 1-octynyl(phenyl)iodonium tosylates do not afford the 1-alkynyl-1H-benzotriazoles but alkenylbenzotriazoles via the reaction of alkylidenecarbenes.
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■ Enantiospecific Total Syntheses of Nuphar Piperidine Alkaloids, (-)-Anhydronupharamine, (-)-Nupharamine, (-)-Nuphenine and (+)-3-Epinupharamine
Toshio Honda,* Fumihiro Ishikawa, and Shin-ichi Yamane
*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
A concise enantiospecific synthesis of nuphar piperidine alkaloids was achieved by employing a regioselective carbon-carbon bond cleavage reaction of the cyclopentane derivative, having a γ-chloro carbonyl system, as a key reaction.
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■ Phenanthridone Analogs of the Opiate Agonist U-47,700 in the trans-1,2-Diaminocyclohexane Benzamide Series
Shikai Zhao, Michael J. Totleben, Stephen A. Mizsak, Jeremiah P. Freeman, and Jacob Szmuszkovicz*
*Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Abstract
The first rigid analog of the opioid trans-1,2-diaminocyclohexane benzamide template was prepared. This analog represented by compound (4b), in a phenanthridone analog of the mu agonist U-47,700 which, historically, was the forerunner of the kappa acetamide U-50,488.
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■ A Convenient Method for the Synthesis of Thiopyrano[2,3-d:6,5-d']dipyrimidine Derivatives
José Ma. Quintela,* María J. Moreira, and Carlos Peinador
*Departamento de Química Fundamental Industrial, Facultad de Ciencias, Universidad de La Coruña, Campus de A Zapateria, s/n, E-15071, La Coruña, Spain
Abstract
A convenient and efficient one-pot synthesis of thiopyrano[2,3-d:6,5-d]dipyrimidine derivatives has been developed. The first solid-state structure elucidation of triheterocyclic system is also reported.
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■ Syntheses of Brominated Bithiazoles and Ethynylation via Palladium-catalyzed Cross-Coupling
Thomas Nussbaumer and Richard Neidlein*
*Pharmazeutisch-Chemishces Institut der Universität Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany
Abstract
The syntheses of brominated 2,2'- and 4,4'-bithiazoles and related 2,2'-bithiazole-5,5'-dicarbaldehyde are described. Palladium-catalyzed cross-coupling of the readily available brominated bithiazoles with acetylenes yields the desired alkynylated bithiazoles. The terminally unprotected ethynyl derivatives can be obtained after removal of the Me3Si protectiong groups under basic conditions.
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■ Synthesis, Isolation, and Dimerization and Trimerization of Monosubstituted Thiophene 1,1-Dioxides
Juzo Nakayama,* Hidehiro Nagasawa, Yoshiaki Sugihara, and Akihiko Ishii
*Department of Chemistry, Faculty of Science, Saitama University, Urawa, Saitama 338-8570, Japan
Abstract
Monosubstituted thiophenes were oxidized with dimethyldioxirane in acetone at -20 °C and then the solvent and volatile materials were removed below -40 °C. This allowed the isolation of kinetically labile 2-methyl-, 3-methyl-, 2-ethyl-, and 2-bromothiophene 1,1-dioxides (3a, 3b, 3c, and 3e, respectively) in practically pure form. These were characterized by 1H- and 13C-NMR, IR. UV/Vis, and MS spectroscopies. The half-lives of the parent thiophene 1,1-dioxide (1), 3b, 3a, and 3c were determined to be 14, 47, 68, and 76 mm, respectively, at 313 K (40 °C) in 0.32 M CDCl3 solutions. The 1,1-dioxide (3a) underwent a [4+2] cyclodimerization in which one molecule of 3a acted as a diene and the other as a dienophile to provide two isomeric products (4a and 5a). In addition, the trimeric product (16a) was formed owing to a further [4+2] cycloaddition of the major isomer (4a) with 3a which took place in the endo and head-to-head mode. Dimeric and trimeric products formation was also observed on decomposition of 3b and 3c, whereas 3e underwent only dimerization.
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■ Synthesis of Fluorine Analogs of Protoporphyrin Potentially Useful for Diagnosis and Therapy of Cancer. Part 3. Synthesis of (2,2-Difluorovinyl)trifluorovinyl- and (1-Chloro-2,2-difluorovinyl)- (2,2-difluorovinyl)deuteroporphyrin
Tsuyoshi Shigeoka, Yasuhisa Kuwahara, Kiyoko Watanabe, Kazuyuki Sato, Masaaki Omote, Akira Ando, and Itsumaro Kumadaki*
*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan
Abstract
Wittig reaction of 3- and 8-formyl deuteroporphyrin dimethyl esters (1 or 2) with triphenylphosphonium difluoromethylide, generated in situ from sodium chlorodifluoroacetate and triphenylphosphine, gave 3- and 8-difluorovinyl compounds (3 or 4), which were iodinated to form corresponding 8- and 3-iodo compounds (5 or 6). Coupling reaction of these iodo compounds with our new bis(fluorovinyl)zinc reagents afforded the titled compounds (7 to 10) in moderate to good yields.
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■ Inhibition of Restriction Endonuclease Cleavage by Triplex Formation with Oligo-2'-O-methyl-ribonucleotides Containing 8-Oxo-2'-O-methyladenosine in Place of Cytidine
Kaoru Ushijima, Toshiaki Ishibashi, Satoru Tsukahara, Kazuyuki Takai, and Hiroshi Takaku*
*Department of Industrial Chemistry, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan
Abstract
The ability of homopyrimidine oligoribonucleotides and oligo-2'-O-methyl-ribonucleotides containing 8-oxo-adenosine (AOH) and 8-oxo-2'-O-methyl-(AmOH) adenosine to form stable, triple-helical structures with sequences containing the recognition site for the class II-S restriction enzyme, Ksp632-I, was studied as a function of pH. The AOH- and AmOH-substituted oligoribonucleotides and oligo-2'-O-methyl-ribonucleotides were shown to bind within the physiological pH range in a pH-independent fashion, without a compromise in specificity. The substitutions of three cytidine residues with AOH showed higher endonuclease inhibition than the substitution of either one or two cytidine residues with AOH. In particular, the oligo-2'-O-methyl-ribonucleotide with only one cytidine substituted with AmOH showed higher endonuclease inhibition. Increased resistance to nucleases is observed with the introduction of 2'-O-methylnucleosides. This stabilization should help us to design much more efficient third strand homopyrimidine oligomer and antisense nucleic acid, which can be used as tools in cellular biology and anti-viral therapy.
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■ A New Synthesis of Benzoporphyrins Using 4,7-Dihydro-4,7-ethano-2H-isoindole as an Isoindole Equivalent
Satoshi Ito, Naoyuki Ochi, Takashi Murashima, Hidemitsu Uno, and Noboru Ono*
*Department of Chemistry, Faculty of Science, Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan
Abstract
Various benzoporphyrins and their metal complexes were obtained in 100% yield by heating porphyrins fused with bicyclo[2.2.2]octadiene at 200 °C. This thermal (retro Diets-Alder) reaction proceeds very cleanly to give pure benzoporphyrins without further purification.
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■ New System for Peptide Synthesis Using N-Acylpyrazoles
Choji Kashima,* Shiro Tsuruoka, and Saori Mizuhara
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
New system of peptide synthesis was described. The extension of one amino acid unit on the peptide chain was constituted from only 2 reaction steps, the conversion from esters to the corresponding N-acylpyrazoles and the subsequent aminolysis with amino esters. This new system was distinctive from the conventional peptide synthesis, which was consisted of 3 steps of the deprotection, the activation and the condensation. Moreover, the key intermediate N-acylpyrazoles exhibited the excellent properties of high sensitivity and separability for the chiral column on HPLC using the UV detector.
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■ Synthesis of N,N'-Unsymmetrical Diacylcystines and Cystine-containing Dipeptides
Eiji Kawanishi, Kyoichi Higuchi, and Akihiko Ishida*
*Medicinal Chemistry Research Laboratory, Tanabe Seiyaku Co.Ltd., 2-2-50, Kawagishi, Toda, Saitama 335-8505, Japan
Abstract
N,N'-Unsymmetrical diacylcystines ((RR)-1 and (SS)-1) were prepared in good yields by three-step reaction sequences starting from cystine diethyl esters ((RR)-5 and (SS)-5). The key step reaction for diacylcystine synthesis, cleavage of diacylcystine diethyl esters ((RR)-2 and (SS)-2) proceeded with no detectable racemization of the products ((RR)-1 and (SS)-1). Cystine-containing dipeptides ((RRS)-3, (RRR)-3, and (SSR)-3) were also prepared in high yields and in high optical purity.
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■ A Convenient Synthesis of Methyl 3-Phenylhydrazono-2-(2-pyrazinylcarbonylamino)propanoates and Their Conversion to Substituted Pyrazol-5(2H)-ones
Vladimir Kepe, Viktor Kozjan, Slovenko Polanc, and Marijan Kočevar*
*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, SI-1000 Ljubljana, Slovenia
Abstract
Methyl 3-dimethylamino-2-(2-pyrazinylcarbonylamino)propenoate (1) was transformed into substituted methyl 3-phenylhydrazono-2-(2-pyrazinyl-carbonylamino)-propanoates (3) by treatment with various substituted phenyl-hydrazine hydrochlorides (2) in methanol. In contrast, heating of 1 and 2 in 1-butanol yielded 1,4-disubstituted pyrazol-5(2H)-ones (4). The latter can also be ob-tained upon heating of 3 in acetic acid.
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■ Reactions of Cage-annulated 2-Methyl-5-(trifluoromethanesulfonyloxy)furans with Lithium Diisopropylamide. Evidence for Nucleophilic Reactivity of LDA
Alan P. Marchand* and Irishi Narayanan Narayanan Namboothiri
*Department of Chemistry, University of North Texas, Texas 76203, U.S.A.
Abstract
Reaction of 3-trifluoromethanesulfonyloxy-5-methyl-4-oxahexacyclo-[5.4.1.02,6.03,10.05,9.08,11]dodecane (6a) with lithium diisopropylamide (LDA, 6 equivalents) in dry THF affords 11-methylenepentacyclo[5.4.0.02,6.03,10.05,9]undecan-8-one (3a) in low yield (11%). This reaction is shown to proceed via formation of an intermediate cage-annulated hemiaminal (7a), which in turn may have resulted via a highly unusual nucleophilic attack by (i-Pr)2N:- upon exo-11-diisopropylamino-endo-11-methylpentacyclo[5.4.0.02,6.03,10.05,9]undecan-8-one (8a). The corresponding reaction of 3-trifluoromethanesulfonyloxy-5,9,10-trimethyl-4-oxahexacyclo[5.4. 1.02,6.03,10.05,9.08,11]dodecane (6b) with LDA (6 equivalents) in dry THF produced 1,7-dimethyl-11-methylenepentacyclo[5.4.0.02,6.03,10.05,9]undecan-8-one (3b) in 10% isolated yield.
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■ Syntheses of Tetraazabis(tropocoronand)s Containing Hydroxy Group(s) and Conformational Analysis of Their Nickel(II) Complexes in Solution
Ohki Sato, Hideki Chikamatsu, Josuke Tsunetsugu,* Kimio Shindo, Hidetsugu Wakabayashi, and (the late) Tetsuo Nozoe
*Department of Chemistry, Faculty of Science, Saitama University, Urawa, Saitama 338-8570, Japan
Abstract
The stepwise syntheses of one symmetric and three asymmetric tetraazabis(tropocoronand)s (12a-12d) having two linker chains, with or without a hydroxy group, of the same or different length are reported. The coordination styles of their nickel(Ö†) complexes (13a-13d) in solution have also been discussed based on their 1H NMR and UV-VIS. spectral data.
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■ Preparation of Iodo-induced 1,3-Oxathiane Compounds via Intramolecular Pummerer Rearrangement of 2-Benzylsulfinylbicyclo[2.2.1]hept-5-ene
Hitoshi Abe,* Hiroyuki Fujii, Natsuko Koshiba, Yasuo Takeuchi, and Takashi Harayama*
*Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
Iodooxathianes (2a and 2b) were prepared from the γ,δ-unsaturated sulfinyl compound (1) via the iodonium-promoted intramolecular Pummerer reaction. A two-step conversion of 1 into 2a and 2b involving iodohydrination and the Pummerer rearrangement was also achieved.
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■ Deuterium Incorporation into Reserpine
Mauri Lounasmaa,* Mathias Berner, Arto Tolvanen, and Reija Jokela
*Laboratory for Organic and Bioorganic Chemistry, Technical University of Helsinki, P.O. Box 6100, FIN-02150 HUT Espoo, Finland
Abstract
Treatment of reserpine (1) with TFA-d under various conditions demonstrated that deuteriurn incorporation proceeds much more slowly than the epimerization. Indirect evidence was thereby obtained for the mechanism of the acid-catalysed epimerization of reserpine (1) that proceeds through C-3-Nb bond cleavage. Furthermore, the effectiveness of TFA as an epimerization reagent was demonstrated.
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■ Reactions of α-Diazocycloalkanones with Thiocarbonyl Compounds
Bashkim Kelmendi, Grzegorz Mloston, and Heinz Heimgartner*
*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Abstract
Reactions of 2-diazocyclohexanone (7) with thioketones and a 1,3-thiazole-5(4H)-thione in THF at 50-60°C in the presence of 10% LiClO4 proceeded by elimination of N2 and yielded 4,5,6,7-tetrahydro-1,3-benzoxathiole derivatives (13-17). In the case of 2,2,4,4-tetramethylcyclobutane-1,3-dithione (12), a 1:5 mixture of cis- and trans- bisadduct (cis/trans-17) was obtained. Under analogous conditions, no reactions occurred with 5,5-dimethyl-2-diazo-cyclo-hexane-1,3-dione (18). Only in the presence of 2% Rh2(OAc)4, 18 reacted with dithione (12) yielding the 1,3-benzoxathiole derivative (19).
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■ Novel Formations of 6-Mesyloxytryptamines and 1-Substituted 3a-(4-Chlorobutoxy)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indoles in the Reaction of Nb-Substituted 1-Hydroxytryptamines with Mesyl Chloride
Masakazu Hasegawa, Yoshiyuki Nagahama, Kensuke Kobayashi, Masumi Hayashi, and Masanori Somei*
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
Formations of 6-mesyloxytryptamines and 1-substituted 3a-(4-chlorobutoxy)-1,2, 3,3a, 8, 8a-hexahydropyrrolo[2,3-b]indoles were newly found in the reactions of Nb-substituted 1-hydroxytryptamines with mesyl chloride in THF. The latter compounds suggest that the intermediate indol-3-yl cations can trap THF and cleave the ether bond.
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■ Heterocycles in Encapsulation and Assembly
Julius Rebek, Jr.*
*The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, U.S.A.
Abstract
Described is the behavior of self-assembled capsules held together by hydrogen bonds. The capsules can be spherical or cylindical and they reversibly encapsulate suitable guest species in organic solvents. Selectivity to molecular shape and length leads to well-defined complexes of two different guests within the capsule. These lead to their use as charge guest species for assembly characterization in the gas phase is also described.