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
Shun-ichi Yamada's Special Issues, Vol. 46, No. 1, 1997
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■ Synthesis of Conformationary Restricted Combretastatins
Ryuichi Shirai, Takuo Okabe, and Shigeo Iwasaki*
*Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Abstract
A series of conformationary restricted heterocyclic combretastatin analogs have been synthesized and their inhibitory activity of microtubule assembly was evaluated. (4S,5S)-4-(4-Methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1,3-dioxolane showed moderate antimitotic activity while its enantiomer and other diastereomers synthesized were inactive.
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■ Enzymatic Resolution of New Anti-inflammatory Drug Etodolac
Eisaku Mizuguchi, Makiko Itanami, and Kazuo Achiwa*
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
Optically active etodolac (1) was easily prepared by lipase-catalyzed kinetic resolution. The unnecessary enantiomer as a by-product of the resolution could be racemized and was converted to a repeated substrate for the enzymatic reaction.
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■ Electronic Effect of Prolinate Ligand-Dirhodium(II) Complexes on Catalytic Asymmetric Dipolar Cycloaddition
Hitoshi Ishitani and Kazuo Achiwa*
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
We prepared several efficient chiral N-benzoylpyrroridinecarboxylic acid ligands for dirhodium-catalyzed asymmetric dipolar cycloaddition and found that the electronic effect of the dirhodium(II) complexes influenced the catalytic activity, and the electron-poor catalysts were shown to be efficient for the reaction. Enantioselectivities of up to 98% ee were attained.
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■ Catalytic Asymmetric Synthesis of Arbutamine
Eiji Takaoka, Naoki Yoshikawa, Yoichi M. A. Yamada, Hiroaki Sasai, and Masakatsu Shibasaki*
*Graduate School of Pharmaceutical Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033
Abstract
An efficient catalytic asymmetric synthesis of (R)-arbutamine has been achieved using a catalytic asymmetric nitroaldol reaction promoted by a heterobimetallic multifunctional asymmetric catalyst as a key step.
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■ Enantioselective Addition of Methyl-lithium to 2-Furaldehyde Imine with the Aid of Chiral Ligand
Daisuke Taniyama, Motomu Kanai, Akira Iida, and Kiyoshi Tomioka*
*Faculty of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
The chiral ligand mediated enantioselective reaction of methyllithium with furylimines was investigated in the presumed 1,4- and 1,2-addition manners. The imines bearing a phosphinoyl or sulfonyl group on the imine nitrogen atom gave rather poor enantioselectivity. On the other hand, the imines bearing a 2-substituted anisidine moiety were found to be the appropriate substrate, giving the corresponding amines with up to 91% ee.
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■ Vitisins D and E, Novel Oligostilbenes from Vitis coignetilae Stem Barks
Kazuhito Shinoda, Yoshiaki Takaya, Tomihisa Ohta, Masatake Niwa, Kanehiko Hisamichi, Mitsuhiro Takeshita, and Yoshiteru Oshima*
*Faculty of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan
Abstract
Phytochemical investigation on oligostilhenes in a methanol extract of Vitis coignetiae (Japanese name: yama-budou) stem barks led to the isolation of novel oxidative resveratrol tetramer and trimer named vitisins D and E, respectively. The structures of the oligostilbenes were characterized on the basis of spectroscopic evidence.
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■ Enantiomerically Pure β-Lactams with the Thienamycin Side Chain via Glycosylation
Bimal K. Banik, Olivia Zegrocka, 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
Easy access to both enantiomers of β-lactarns with the thienamycin side chain was achieved via iodine catalyzed Ferrier reaction with commercially available tri-O-acetyl-D-glucal.
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■ A One Step Conversion of Sulfoxides to Aldehydes by the Neighboring Group Participation in the Pummerer Rearrangement of ortho-Hydroxymethyl Aryl Benzyl Sulfoxides
Hiroyuki Naka, Soichi Sato, Ernst Horn, and Naomichi Furukawa*
*Tsukuba Advanced Research Alliance Center, Department of Chemistry, University of Tsukuba, Tsukuba, Ibaraki 305, Japan
Abstract
Benzyl 2-(hydroxymethyl)phenyl sulfoxides (1) treated with p-toluenesulfonic acid monohydrate (TsOH·H2O) undergo the Pummerer-type rearrangement to give benzaldehydes in one step. The reaction was found to proceed via the oxosulfonium salt (6) as an intermediate.
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■ Solvent Free Synthetic Procedure throughout Reaction and Separation: Ylide Reaction with Alkyl Aryl Ketones in the Absence of Solvent Followed by Distillation to Give 1-Alkyl-1-aryloxiranes
Fumio Toda* and Kazuyuki Kanemoto
*Department of Applied Chemistry, Faculty of Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama, 790-8577 Ehime, Japan
Abstract
After heating a mixture of trimethylsulphonium iodide, t BuOK and an alkyl aryl ketone at 60-70 °C for 1-5 h, vacuum distillation gave the corresponding 1-alkyl-1-aryloxirane. The procedure was accomplished without using any solvent throughout the reaction and the separation.
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■ The Highly Enantioselective Borane Reduction of Ketones Catalyzed by Chiral Oxazaborolidine Derived from Sterically Constrained Amino Alcohols
Noriaki Hashimoto, Tadao Ishizuka , and Takehisa Kunieda*
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
Reagents generated in situ from the borane-tetrahydrofuran complex and conformationally rigid and sterically congested amino alcohols (3, 4), as well as oxazaborolidines (5, 6), catalyze the smooth reduction of prochiral ketones to the secondary alcohols with excellent enantiomeric excess.
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■ Synthetic Approach toward the Development of New β-Lactamase Inhibitors
Yoshimitsu Nagao,* Toshio Kumagai, Shigeaki Kobayashi, Satoshi Tamai, Kei-ichiro Ohta, Yoshinori Inoue, and Ikuo Kishi
*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Abstract
New racemic thienamonobactams (21) and (28), designed on the basis of hybridization between thienamycin (5) and aztreonam (6), were successfully synthesized by exploiting the [2+2] cycloaddition reaction of diketene with imine (7) Compound (28) exhibited significant inhibitory activity (ID50 =37 μM) against Citrobacter freundii cephalosporinase.
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■ Syntheses of 4-Substituted 3,5-Dihydro-1H-thieno[3,4-c]pyrrole 2,2-Dioxides and Their Diels-Alder Reactions
Takayoshi Suzuki,* Hiroaki Ohyabu, and Hiroaki Takayama
*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan
Abstract
The preparation of 4-substituted 3,5-dihydro-1H-thieno[3,4-c]pyrrole 2,2-dioxides and their intermolecular Diels-Alder reactions with DMAD are described. In the reaction with DMAD, 4-acetyl-3,5-dihydro-1H-thieno[3,4-c]pyrrole 2,2-dioxides acted as the corresponding 3,4-dimethylenepyrroles.
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■ Synthetic Studies on Clerodane Diterpenoids. 3. An Alternative Synthesis of an Unnatural Antifeedant
Hsing-Jang Liu* and Naim H. Al-Said
*Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
Abstract
An alternative synthesis of (1S*,2S*,6R*,10S*)-2-acetoxy-lacetoxymethyl-5,5-dimethylbicyclo[4.4.0]decane-10-spiro-2’-oxirane (1), an unnatural antifeedant, has been effected via an intermolecular Diels-Alder approach.
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■ Direct Synthesis of Heteroarylethynes via Palladium-catalyzed Coupling of Heteroaryl Halides with Ethynylzinc Halides. Its Application to an Efficient Synthesis of a Thiophenelactone from Chamaemelum nobile L.
Ei-ichi Negishi,* Caiding Xu, Ze Tan, and Martin Kotora
*Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, U.S.A.
Abstract
A variety of terminal alkynes containing a heteroaryl group can be directly and selectively synthesized by the Pd-catalyzed coupling of heteroaryl iodides or bromides with ethynylzinc halides. Various compounds of this class containing furan, thiophene, and pyridine have been prepared, and the procedure has been applied to an efficient and selective synthesis of a thiophenelactone from Chamaemelum nobile L.
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■ N-Glycosylation with Glycosyl Diethyl Phosphites: A Highly Stereoselective Synthesis of 2'-Deoxy-β-ribonucleosides
Shun-ichi Hashimoto,* Jun Inagaki, Hiroki Sakamoto, Ai Sano, and Makoto Nakajima
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
A facile and direct method for the construction of 2’-deoxy-β-N-glycosidic linkages in 2’-deoxyribonucleoside synthesis has been developed by using 3-(3,4,5-trimethoxybenzoyl)-protected 2-deoxyribofuranosyl diethyl phosphites as a glycosyl donor in the presence of trimethylsilyl triflate, wherein coupling reactions with silylated pyrimidine bases have been found to exhibit β-selectivities up to 96%.
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■ An α-Selective Glycosylation via Decarboxylation of Mixed Carbonate Catalyzed by the Combination of Lewis Acid and Silver Perchlorate
Takamasa Iimori, Isao Azumaya, Takafumi Shibazaki, and Shiro Ikegami*
*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan
Abstract
A catalytic amount of SnCl4-AgClO4 or Cp2HfCl2-2AgClO4 promoted decarboxylation of the 1-O-carbonates of the sugars to afford the α-glycosides stereoselectively. In this glycosylation reaction, the carbonate acts a leaving group of the glycosyl donor and also a cap of hydroxyl group in the acceptor alcohol.
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■ Reaction of N-Aminophthalimide Derivatives with Aluminum Chloride in Benzene
Atsushi Ohwada, Hao Li, Takeshi Sakamoto, and Yasuo Kikugawa*
*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
Abstract
The reaction of N-aminophthalimide derivatives with AlCl3 in benzene has been investigated. From N-amino- and N-benzamidophthalimide (1a and 1b), N-amino- and N-benzamido-3,3-diaryl-2,3-dihydroisoindol-1-ones (2) are obtained in high yield by initial attack of benzene on the imide carbonyl, assisted by the neighboring nitrogen atom. From N-arylaminophthalimide derivatives (4), the N-N bond is cleaved heterolytically to give an arylnitrenium ion and canonical forms involving the arene which are trapped by benzene to give aminobiaryls and N-arylanilines.
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■ Asymmetric Synthesis of Various Chiral 5-Pyrimidylalkanols by the Enantioselective Alkylation of Pyrimidine-5-carbaldehydes with Dialkylzincs in the Presence of Chiral Amino Alcohols
Takanori Shibata, Tadakatsu Hayase, Yasuyuki Aiba, Hayami Tabira, and Kenso Soai*
*Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan
Abstract
(1S, 2R)-N,N-Dibutylnorephedrine catalyzes the enantioselective addition of dialkylzincs to various pyrimidine-5-carbaldehydes. Ethylation and butylation proceed with high enantioselectivities (up to 94% e.e.) to give optically active secondary 5-pyrimidyl alkanols.
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■ Synthesis of Taxoids II. Synthesis and Antitumor Activity of Water-soluble Taxoids
Naoyuki Harada, Kunihiko Ozaki, Tetsuo Yamaguchi, Hiroaki Arakawa, Akira Ando, Kouji Oda, Noriyuki Nakanishi, Motoaki Ohashi, Tomiki Hashiyama,* and Kenji Tsujihara*
*Lead Optimization Research Laboratory, Tanabe Seiyaku Co.Ltd., 2-2-50, Kawagishi, Toddda, Saitama 335-8505, Japan
Abstract
Synthesis of novel taxoid water-soluble prodrugs that have 2’-substituted amino acid derivatives with spacer is described. Enantioselective synthesis of the C-13 side chains proceeded through the asymmetric dihydroxylation. Several compounds had good solubility in saline and showed potent antitumor activity against B16 melanoma in mice.
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■ Optical Resolution of (2,2,2-Trifluoro-1-hydroxyethyl)deuteroporphyrins
Masaaki Omote, Takashi Matsumoto, Akira Ando, Toshiyuki Takagi, Mayumi Koyama, and Itsumaro Kumadaki*
*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan
Abstract
Optical resolution of 3- and 8-(2,2,2-trifluoro-1-hydroxyethyl)-deuteroporphyrin dimethyl esters (2 and 3) were accomplished through their (1S)-camphanyl esters. Thus, these esters were easily resolved by column chromatography. Each camphanyl ester was cleaved with sodium bis(trimethyl-silyl)amide - THF - MeOH. The resolved dimethyl esters were hydrolyzed by sodium hydroxide. The sodium salt of 2- (S) was taken up by cancer cells about 15 times more than that of 2-(R), while the salt of 3-(R) was taken up more than that of 3-(S).
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■ Synthesis of New Chiral Catalysts, Isoquinuclidinylmethanethiols, for the Enantioselective Addition of Diethylzinc to Aryl Aldehydes
Hiroto Nakano, Kazuto Iwasa, and Hiroshi Hongo*
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
New chiral ligands, isoquinuclidinylmethanethiols, were prepared and their catalytic abilities of asymmetric induction were examined in the addition of diethylzinc to aldehydes to furnish secondary alcohols in up to 94% ee.
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■ Preparation of α-Methylene-γ-butyrolactones wtih Difluoromethylene Functionalities
Hiroshi Fukuda and Tomoya Kitazume*
*Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatuta-cho, Midori-ku, Yokohama 226-8501, Japan
Abstract
4-(1,1-Difluoro-2-ethoxycarbonyl)methyl-γ-butyrolactone (1) was prepared from the Reformatsky-type reaction of n-butyl 3-formylpropanoate with ethyl bromodifluoroacetate in Zn-THF system, and compound (1) was converted to α-methylene-γ-butyrolactone derivatives with a difluoromethylene unit at γ-position.
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■ Total Synthesis of (-)-Stemoamide Using Ruthenium-catalyzed Enyne Metathesis Reaction
Atsushi Kinoshita and Miwako Mori*
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
A total synthesis of (-)-stemoamide was achieved from (-)-pyroglutamic acid using a ruthenium-catalyzed enyne metathesis as a key step, in 14 steps in 9% overall yield.
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■ Crude Drugs from Aquatic Plants. VII. Four New Thiaspirane Sulfoxide Type Nuphar Alkaloids, Nupharpumilamines A, B, C, and D, from Chinese Nupharis Rhizoma, the Rhizoma of Nuphar pumilum (TIMM.) DC. (Nymphaceae)
Masayuki Yoshikawa,* Toshiyuki Murakami, Atsushi Ishikado, Shuji Wakao, Nobutoshi Murakami, Johji Yamahara, and Hisashi Matsuda
*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan
Abstract
Following the characterization of thiohemiaminal type nuphar alkaloids with immunosuppressive activity, four new thiaspirane sulfoxide type dimeric sesquiterpene alkaloids, nupharpumilamines A, B, C, and D, were isolated from Chinese Nupharis Rhizoma, the dried rhizoma of Nuphar pumilum (TIMM.) DC. The structures of nupharpumilammes A, B, C, and D were determined on the basis of chemical and physicochemical evidence.
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■ Synthesis and Antitumor Evaluationof Octahydro-5-hydroxy-1,5-imino-3-benzazocin-4,7,10-triones
Naoki Saito, Haruyuki Sakai, Erika Takai, Riho Muranaka, Michiko Itabashi, Akinori Kubo,*Katsukiyo Yazawa, and Yuzuru Mikami
*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Abstract
1,2,3,4,5,6,7,10-Octahydro-5-hydroxy-1,5-imino-3-benzazocin-4,7,10-trione (3a) was synthesized from the hexahydro-1,5-imino-9-methoxy-3,8,11-trimethyl-4-oxo-3-benzazocine (4a) in six steps and evaluated for its antitumor activity against L1210 in vitro.
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■ A Formal Synthesis of (+)-α-Allokainic Acid via Sulfanyl Radical Addition-Cyclization Reaction
Okiko Miyata, Yoshiki Ozawa, Ichiya Ninomiya, Keiichi Aoe, Hajime Hiramatsu, and Takeaki Naito*
*Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan
Abstract
Sulfanyl radical addiuon-cyclization of the diallylamines in the presence of thiophenol and AIBN gave the 2,3,4-uisubstituted pyrrolidines which were effectively converted into the known key intermediate for the synthesis of (+)-α-allokainic acid via conversion of the phenylsulfanylmethyl group into the isopropenyl group at the 4-position.
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■ Novel Route to the Synthesis of Hydroxylated Pyrrolidine Derivatives via the Intramolecular Reaction of γ-Aminoallylstannane with Aldehyde. Total Synthesis of (+)-Preussin
Isao Kadota, Shioko Saya, and Yoshinori Yamamoto*
*Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
The thermal cyclization of γ-aminoallylstannane (8) having an aldehyde group gave β-hydroxypyrrolidine derivative (9a) as a sole product. This methodology was applied successfully to the total synthesis of (+)-preussin.
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■ New Asymmetric Synthesis of Enantiomeric Pairs of the 2-Substituted Pyrrolidines Bgugaine and Irniine
Hiroki Takahata,* Kozue Ihara, Minoru Kubota, and Takefumi Momose*
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
A new asymmetric route to 2-substituted pyrrolidines starting with the Sharpless asymmetric dihydroxylation (AD) of 4-pentenylphthalimide (5) followed by aminocyclization of the resultant amino alcohol is presented. The application to the asymmetric synthesis has been examined for two 2-substituted pyrrolidine alkaloids, bgugaine (1) and imiine (2).
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■ Synthesis of C-Ring Modified Analogues of Camptothecin
Ryuji Yoneda, Tetsuya Kimura, Shinya Harusawa, and Takushi Kurihara*
*Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
Abstract
Aiming at developing novel antitumor active compounds, we designed hexahydropyrano[3”, 4”; 3’, 4’]pyrido[5’, 6’; 4, 5]cyclopenta[1, 2-b]-quinoline which is a C-ring modified analogue of camptothecin. me compounds (9-14) were synthesized via Friedländer condensation and their in vitro cytotoxic activities were tested.
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■ Halogen Exchange Reaction of Optically Pure Halotelluranes
Shigemasa Takahashi , Jian Zhang, Shinichi Saito, and Toru Koizumi*
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
A series of optically pure chlorotelluranes (2a-c) has been prepared by using the 2-exo-hydroxy-10-hornyl group as a chiral ligand. Fluoro, bromo, and iodotelluranes (1,3, and 4) were also prepared by the halogen exchange reaction of 2 in the presence of NaX, AgX, or tetrabutylammonium halide (TBAX) (X = halogen). The retention of the stereochemistry of chiral tellurium atom was observed throughout the reaction. An SN1 pathway was proposed as the mechanism of this halogen exchange reaction.