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
Koji Nakanishi's Special Issues, Vol. 47, No. 2, 1998
Published online:
■ Formation of Selenetanes from 2-(3-Hydroxyalkylseleno)-benzoxazoles
Kazunori Takemura, Kunihiko Sakano, Ayuko Takahashi, Toshimi Sakamaki, and Oyo Mitsunobu*
*Department of Chemistry, College of Science and Engineering, Aoyama Gakuin University, 6-16-1 Chitosedai, Setagayaku, Tokyo 157-8572, Japan
Abstract
The reaction of 2-(3-hydroxyalkylseleno)benzoxazoles with KH afforded the corresponding selenetanes and 2(3H)-benzoxazolone.
Published online:
■ Tetracyclic Isoquinolones and Quinazolones via Aryl Radical Cyclizations
Bimal K. Banik, Vegesna S. Raju, Maghar S. Manhas, and Ajay K. Bose*
*Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Castle Point on the Hudson, Hoboken, NJ 07030, U.S.A.
Abstract
The Schiff base from o-bromobenzaldehyde and allylamine was allowed to react with homophthalic anhydride to form an isoquinolone. Reaction of the same Schiff base with isatoic anhydride led to a quinazolone. Generation of a free radical from the bromoaryl moiety under the influence of tributyltin hydride converted the isoquinolone and the quinazolone to tetracyclic systems. This approach can lead to a convenient synthesis of alkaloids of the benzophenanthridine and protoberberine families.
Published online:
■ An Antimalarially Active Cyclic Peroxy Ketal
Gary H. Posner* and Hardwin O'Dowd
*Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, U.S.A.
Abstract
Cyclic peroxy ketal (1), prepared using the Snider photoenolization-oxygenation procedure, has been found to have measurable antimalarial activity. Upon reaction with ferrous ions, peroxide (1) is converted mainly into hydroxylated epoxy ketone (6), and a mechanism involving several intermediates including a high-valent iron-oxo species is proposed to account for this chemical transformation.
Published online:
■ Oxidation of Marchantin A Trimethyl Ether and Related Aromatic Compounds with m-Chloroperbenzoic Acid
Motoo Tori,* Masakazu Sono, Masao Toyota, and Yoshinori Asakawa*
*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-machi, Tokushima, 770-8514, Japan
Abstract
Marchantin A trimethyl ether was subjected to react with m-chloroperbenzoic acid to yield hydroxylated derivatives as well as ring C degraded esters. This reaction was confirmed by application to catechol dimethyl ether and dihydroeugenol dimethyl ether.
Published online:
■ Synthesis of Medium-Size Lactones from Alkyne Using Chromium Carbene Complex
Miwako Mori,* Takashi Norizuki, and Taro Ishibashi
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
Reaction of alkynes having the hydroxy group in a tether with choromium carbene complex gave medium-size lactones in good to moderate yields. The two geminal substituents in a chain affect the yield of the lactones.
Published online:
■ A Facile Aldol-Isomerization Route to 3-Alkyldihydropyridinone with a Chiral Azocine Ring
Yasuhiro Torisawa, Than Soe, Chiaki Katoh, Yumiko Motohashi, Atsushi Nishida, Tohru Hino, and Masako Nakagawa*
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
An efficienf profocol was devised for the synthesis of the chiral dihydropyridinone derivative (19), which involves an aldol-type coupling reaction between N-alkylpiperidin-2-one and Garner aldehyde followed by silane-Rh-mediated olefin isomerization.
Published online:
■ Tautomerism of Clitidine, a Pyridine Nucleoside from the Poisonous Mushroom Clitocybe acromelalga
Haruhisa Shirahama,* Hiroyuki Koshino, Jun Uzawa, Kimiaki Yamano, Katsuhiro Konno, and Kazumi Nakatsu
*School of Science, Kwansei Gakuin University, 1-1-155 Uegahara, Nishinomiya 662-8501, Japan
Abstract
Tautomerism of clitidine (1a), a toxic pyridine nucleoside from the poisonous mushroom Clirocybe acromelalga, was investigated by 15N NMR spectroscopy in aqueous solution and by X-Ray crystallographic analysis in the solid state, which showed the tautomer (1d) to be predominant in both states.
Published online:
■ Reaction of Maleimides with New Silyloxydienes, 2-Amino- 4-(trimethylsilyloxy)-1,3-pentadienes
Otohiko Tsuge,* Taizo Hatta, Yamato Takahashi, Hironori Maeda, and Akikazu Kakehi
*Graduate Course of Applied Chemistry, Faculty of Engineering, Kumamoto Institute of Technology, 4-22-1, Ikeda, Kumamoto 860, Japan
Abstract
New siloxydienes, 2-amino-4-(trimethylsilyloxy)-1,3-pentadienes which were easily obtained via enolization of enaminones derived from 2,4-pentane-dione, and immediate silylation, reacted with maleimides to furnish reduced benzo[c]pyrrole-1,3-diones as major products, derived from initial [4 + 2] cycloadducts.
Published online:
■ A New Synthetic Approach to a Fungal β-Lactone Based on the Asymmetric [2,3]-Wittig Rearrangement
Katsuhiko Tomooka, Takahiro Takeda, Au Wing Kuen, and Takeshi Nakai*
*Department of Chemical Technology, Faculty of Engineering, Tokyo Institute of Technology, Meguro-ku, Tokyo 152, Japan
Abstract
An asymmetric synthesis of the chiral β-lactone precursor of the HMG-CoA synthase, inhibitor L-659,699, is described, which involves as the key step an asymmetric [2,3]-Wittig rearrangement to control the stereogenic centers at the ring carbons (C2’ and C3’).
Published online:
■ A Practical Synthesis of the Key Intermediate for Theopederins—An Enantioselective Total Synthesis of (+)-Methyl Pederate
Masahiro Toyota,* Youichi Nishikawa, and Keiichiro Fukumoto
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
A practical synthesis of the key intermediate for theopederins, methyl pederate (15), has been accomplished by means of palladium-catalyzed reactions.
Published online:
■ anti-Selective Epoxidation of Primary 5-(tert-Butyldimethylsilyl)oxyallylic Alcohols with m-Chloroperoxybenzoic Acid
Kåre B. Jørgensen, Hiroyuki Koshino, and Tadashi Nakata*
*The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan
Abstract
Epoxidation of primary 5-(tert-butyldimethylsilyl)oxyallylic alcohols with m-chloroperoxybenzoic acid produced anti-epoxides with high stereoselectivity.
Published online:
■ Synthesis and Structure of Glycosylidene Acetals of Galactoside
Hiro Ohtake, Takamasa Iimori, Moto Shiro, and Shiro Ikegami*
*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan
Abstract
Interglycosidic spiro-orthoesters were efficiently prepared from methyl 2,6-di-O-benzylgalactopyranoside and sugar lactones in the presence of methoxytrimethylsilane and a catalytic amount of trimethylsilyl triflate. The structure of the prepared orthoester, galactosylidenegalactoside, was determined by X-Ray crystallographic analysis.
Published online:
■ The Preparation of Heterocyclic Appended Vinylogous Iminium Salts and Their Application to the Regioselective Preparation of Biheterocyclic Systems
John T. Gupton,* Scott A. Petrich, Fred A. Hicks, Doug R. Wilkinson, Marian Vargas, Kirsten N. Hosein, and James A. Sikorski*
*Department of Chemistry, University of North Carolina at Asheville, Asheville, North Carolina 28804, U.S.A.
Abstract
The synthesis of heterocyclic appended vinylogous iminium salts is described along with their conversion to heterocyclic appended pyrimidines, triazolopyrimidines, and pyrroles.
Published online:
■ Synthesis of N-Substituted 3-Oxo-17β- carboxamide-4-aza-5α-androstanes and the Tautomerism of 3-Oxo-4-aza-5-androstenes
Peng Xia,* Zheng-yu Yang, Yi Xia, Hao-bing Zhang, Ke-hua Zhang, Xun Sun, Ying Chen, and Yun-qing Zheng
*Department of Organic Chemistry, School of Pharmacy, Shanghai Medical University, 138 Yi Yuan Road Shanghai 200032, China
Abstract
An N-aryl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide and three N-aryl or alkyl substituted 17 α-hydroxy-3-oxo-4-aza-5α-androstane-17β-carboxamides were synthesized as antiandrogen candidates from 3-oxoandrost-4-ene-17β-carboxylic acid and androst-4-ene-3,17-dione respectively. The chemo- and stereoselective reduction of 3-oxo-4-aza-5-ene intermediates with formic acid and their tautomerism in a solution of chloroform and methanol were described.
Published online:
■ Photolysis of 13C-Methylcobalamin. Direct Detection of Generated Formaldehyde by Using 13C-Labeling
Kazuhiko Takatori, Yoshifumi Nakajima, Miyako Hirose, and Masahiro Kajiwara*
*Department of Medicinal Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Abstract
Photolysis of methylcobalamin was followed by UV, CD and 1H-NMR spectroscopic methods. The direct detection of formaldehyde as a photolysis product was achieved by 13C-NMR using 13C-methylcobalamin, prepared from vitamin B12 and 13C-methyl iodide, as a substrate.
Published online:
■ Enantioselective Access to Five- and Six-membered Nitrogen-containing Heterocycles, Based on the Asymmetric Michael Addition of Chiral Imines and Chiral Enamino Esters
Jean d'Angelo,* Christian Cavé, Didier Desmaële, Abdoulaye Gassama, Cyrille Thominiaux, and Claude Riche
*Unité de Chimie Organique Associé au CNRS, Centre d'Etudes Pharmaceutiques, Université de Paris-Sud, 5, rue Jean-Baptiste Clément, 92296 Chatenay-Malabry Cedex, France
Abstract
The addition reaction of chiral imines, (ent-10,48,70) and chiral enamino esters (52, 55, 73) with maleic anhydride (32), citraconic anhydride (57), α-chloroacrylonitrile (29), and nitroethylene (74), has been investigated. These condensations proved to be in general highly regio-, diastereo-, and enantioselective. In most cases the primary adducts underwent an in situ N-heterocyclization, allowing the enantioselective access to nitrogen-containing, five- and six-membered heterocycles.
Published online:
■ A Novel Route to Chiral Non Racemic 2-Substituted 1,2,3,4-Tetrahydroquinolines
Marie-Christine Lallemand, Mathieu Gaillard, Nicole Kunesch,* and Henri-Philippe Husson*
*CNRS-URA 1310, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 4, avenue de l'Observatoire, 75270 Pairs Cedex 06, France
Abstract
The chiral non racemic α-cyanopiperidine (1) and its α-methyl derivative (4) react with activated alkynes. Depending on the reaction conditions, Michael adducts are obtained. Moreover, synthon (4) gives access to the 1,2,3,4-tetrahydroquinoline framework in one step. The substitution pattern on the aromatic ring depends on the alkyne. This constitutes a new and short synthetic method of chiral non racemic 1,2,3,4-tetrahydroquinolines.
Published online:
■ Carbocyclic 7-Deazaguanine Oxetanocin Analogues
Jayu Wu, Stewart W. Schneller,* Katherine L. Seley, and Erik De Clercq
*Department of Chemistry, Auburn University, Auburn, AL 36849-5312, U.S.A.
Abstract
The synthesis of two carbocyclic 7-deazaguanosine oxetanocins structurally modified at the C-3’ center and lacking the C-2’ hydroxymethylene group is described. Neither of these target compounds showed antiviral activity against a battery of DNA and RNA viruses.
Published online:
■ Radical Reaction Initiated and Stereocontrolled by Zinc Chloride
Yoshinori Yamamoto,* Setsuko Onuki, Masatoshi Yumoto, and Naoki Asao
*Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
The reaction of allyltributyltin with methyl 2-[N-((4S)-4-(1-methylethyl)-2-oxazolidione-3-carbamoyl)amino]-2-bromoacetate (5a) was accelerated at -50°C in the presence of AIBN and stopped in the presence of galvinoxyl, indicating that the reaction proceeds through a radical mechanism. The reaction was accelerated dramatically at -78°C in the presence of ZnCl2·OEt2, and the ZnCl2-mediated reaction was stopped in the presence of galvinoxyl. In the presence of 2 equiv ZnCl2·OEt2, the reaction afforded methyl (2R)-2-[N-((4S)-4-(1-methylethyl)-2-oxazolidinone-3-carbamoyl)amino]-4-pentenoate {6a(R)} with high diastereoselectivity (93:7). Taken together, ZnCl2·OEt2 works as a radical initiator as well as chelating agent.
Published online:
■ 1,3-Dipolar Cycloadditions with 1-Alkoxy-substituted Nitrile Ylides
Nina Bojkova and Heinz Heimgartner*
*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Abstract
Thermolysis of 4-alkoxy-1,3-oxazol-5(2H)-ones (2) (X = O) leads to reactive nitrile ylides (1) bearing an alkoxy substituent at the nitrile C-atom. These intermediates can be trapped by C,C-, C,O-, C,N-, and C,S-dipolarophiles, yielding 5-membered heterocycles via 1,3- dipolar cycloaddition. In the case of 1,3-thiazole-5(4H)-thiones (11) as dipolarophiles, two regioisomeric cycloadducts were obtained. The results of the cycloadditions are discussed with respect to the influence of the alkoxy substituent on the structure of the nitrile ylide.
Published online:
■ X-Ray Crystallographic Analysis of 2,5-Bis(diphenylmethylsilyl)thiophene Monooxide and the Diels-Alder Reaction of Thiophene Monooxide with Dienophiles
Naomichi Furukawa,* Shao-Zhong Zhang, Ernst Horn, Ohgi Takahashi, Soichi Sato, Masataka Yokoyama, and Kentaro Yamaguchi
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
X-Ray crystallographic analysis of 2,5-his(diphenylmethylsilyl)thiophene monooxide revealed that the thiophene ring is not a planar structure and that the S-O bond is tilted ca. 14° out of the ring plane. The Diels-Alder reaction of 2,5-bis(trimethylsilyl)thiophene with dienophiles gave the adducts in high yields. The stereochemical courses for the reactions are exclusively endo-orientation and syn-direction with respect to the S-O bond. This stereochemistry agrees with the results obtained from RHF and MP2 MO calculations using the 6-31G(*) basis set.
Published online:
■ ortho-Directed Lithiation Studies of 4-Chloropicolinanilide : Introduction of Functional Groups at C-3 and Their Elaboration to Chain Extended Derivatives via Carbon-Carbon Bond Formation
Marcus V. Nora de Souza and Robert H. Dodd*
*Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France
Abstract
An improved synthesis of 4-chloropicolinanilide (3) is presented. Treatment of 3 with lithium diisopropylamide (LDA) in THF, followed by addition of an electrophile (methyl iodide, iodine, carbon dioxide, trimethylstannyl chloride), gave exclusively the products of C-3 substitution (respectively, the 3-methyl-, 3-iodo, 3-carboxylic acid and 3-trimethylstannyl derivatives of 3). Further treatment of the 3-methyl derivative (7) with carbon dioxide or ethyl bromoacetate produced the one- and two-carbon homologues of 4-chloroquinolinanilide (8 and 9, respectively). The palladium acetate-catalyzed reaction of 4-chloro-3-iodopicolinanilide (10) with various unsaturated derivatives (trimethylsilylacetylene, tri-n-hutyl(vinyl)tin, styrene, acrylonitrile, methyl acrylate) afforded the corresponding C-3 cross-coupled products in 70-80% yield. Reaction of 10 with allyl alkoxide, followed by treatment of the product (17) with tri-n-butyltin hydride, provided the 2-methylfuro[3,2-c]pyridine derivative (18) in 85% yield.
Published online:
■ Thermal and Chemiluminescent Property of Dioxetanes Having an N-Arylacridane Structure
Takeshi Imanishi,* Yohko Ueda, Ryoh Tainaka, Naoto Kuni, Masatoshi Minagawa, Nobuhiro Hoshino, and Kazuyuki Miyashita
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
Novel dioxetanes having an N-arylacridane structure were synthesized. Studies on thermal stability and chemiluminescent property of these compounds showed that the aryl group cannot stabilize the dioxetane structure so much but can trigger the chemiluminescence by formation of the phenoxy anion.
Published online:
■ Synthesis of (+)- and (-)-Ethosuximides Utilizing Asymmetric Nitroolefination
Kiyoharu Nishide, Takahiro Katoh, Hitoshi Imazato, and Manabu Node*
*Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
Abstract
Both enantiomers of ethosuximide were synthesized from (S)-(-)- and (R)-(+)-2-methyl-2-[(E)-2-nitroethenyl]-γ-butyrolactones (1), which were obtained by asymmetric nitroolefination of α-methyl-γ-butyrolactone, via the lactone carboxylic acid (3).
Published online:
■ Synthesis and Photoswitchable Complexation/Extraction Properties of Lipophilic Azabis(benzo-15-crown-5) Ionophores for Alkali Metal Cations
Kazunori Odashima,* Koji Tohda, Shinji Yoshiyagawa, Shinichiro Yamashita, Masamitsu Kataoka, and Yoshio Umezawa*
*Graduate School of Pharmaceutical Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033
Abstract
Novel lipophilic derivatives of azobis(benzo-15-crown-5) (1b, 1c) were synthesized and their photoisomerization, complexation and extraction properties for alkali metal cations were investigated. Upon UV light irradiation, the photostationary state of the trans and cis isomers was reached and, with both 1b and 1c, the extractabilities of Rb+ and Cs+ increased due to the formation of 1:1 sandwich-type complexes by the cis isomers. On the other hand, the extractability of K+ decreased, possibly because the 2:1 complexes formed by the trans isomers are more stable and/or lipophilic than the complexes of the cis isomers.
Published online:
■ A Facile One-Pot Synthesis of 4-Alkoxy-1,3-benzenedicarbonitrile
Masaichi Hasegawa
*Teijin Institute, Bio-Medical Research, Asahigaoka 4-3-2, Hino, Tokyo 191, Japan
Abstract
2-(3-Cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxlic acid (TEI-6720) was prepared. The introduction of cyano group to 4-nitrobenzonitrile with KCN in dry DMSO followed by quenching with alkyl halide afforded the key intermediates, 4-alkoky-1,3-benzenedicarbonitriles, in good yield. The reaction was completed in dry DMSO, while no reaction occurred in dry DMF. This observation can be suggested by the participation of DMSO in the reaction.
Published online:
■ Photooxidative Decarboxylation of Proline, a Novel Oxidative Stress to Natural Amines
Katsuya Endo,* Kaoru Hirayama, Yuko Aota, Kazuhiko Seya, Hirotatsu Asakura, and Kanehiko Hisamichi
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
Proline was decarboxylated quantitatively to Δ1-pyrroline on photoirradiation in the presence of rose bengal, while its methyl ester yielded an equimolar mixture of Δ1- and Δ5-pyrroline-2-carboxylic acid methyl esters. The decarboxylation of proline took place under either an aerobic ( O2 bubbling ) or an anaerobic ( N2 bubbling) conditions, and under the latter condition, extent of the reaction depended on the amount of rose bengal employed. These results imply mechanistically that the reaction is the Type I photooxidation, indicating a new type of oxidative stress to natural secondary amines.
Published online:
■ Convenient Synthesis of Pyrido[4,3-d]-pyrimidine-2,4(1H,3H)-diones
Kosaku Hirota,* Yukio Nakazawa, Yukio Kitade, and Hironao Sajiki
*Labolatory of Medicinal Chemistry, Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
A convenient synthesis of pyrido[4,3-d]pyrimidine-2,4(1H,3H)-diones is described. Treatment of 5-formyl-1,3-dimethyl-6-(2-dimethylamino)vinyluracil (1) with ammonia and hydrazines affords the corresponding pyrido[4,3-d]pyrimidine-2,4(1H,3H)-diones (2 and 3), respectively. Similar reaction of 5-cyano- and 5-ethoxycarbonyluracils (10 and 15) with ammonia led to formation of 5-amino- and 5-hydroxylpyrido[4,3-d]pyrimidine-2,4(1H,3H)-diones (11 and 16), respectively.
Published online:
■ Lepiotins A and B, New Alkaloids from the Mushrooms, Macrolepiota neomastoidea and Chlorophyllum molybdites
Tomihisa Ohta,* Hiroyuki Inoue, Genjiro Kusano, and Yoshiteru Oshima
*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
Two new alkaloids, lepiotins A and B were isolated from the poisonous mushrooms Macrolepiota neomastoidea and Chlorophyllum molybdites, which were classified to family Agaricaceae. These structures were determined on the basis of a spectroscopic analysis and a synthetic study.
Published online:
■ On the Chlorine Addition to the C(5)-C(6) Bridge and the N-Oxidation of 1,10-Phenanthroline
Róza Antkowiak and Wieslaw Z. Antkowiak*
*Facluty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznán, Poland
Abstract
It was found that under the influence of aqueous hypochlorite 1,10-phenanthroline (1) is initially transformed into 5,6-dichloro-5,6-dihydro-1,10-phenanthroline (2) and 5-chloro-6-hydroxy-5,6-dihydro-1,10-phenanthroline (8). The latter readily undergoes subsequent transformations either into a mixture of 5,5-dichloro-6-oxo-5,6-dihydro-1,10-phenanthroline (4) and 5,6-dioxo-5,6-dihydro-1,10-phenanthroline (5) or into the known 5,6-epoxy-1,10-phenanthroline (3) depending on the acidic or alkaline conditions, respectively. In contrast to the flat molecule of the starting 1, that of the dichloro derivative (2) being twisted at the central bond of the bipyridine system can be easily N-oxidized to di-N-oxide (11). Both 2 and its di-N-oxide (11) in the presence of sodium isopropoxide at 0°C freely lost hydrogen chloride and returned to the fully aromatic system of 5-chloro-1,10-phenanthroline (9) and its di-N-oxide (13), respectively.