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
Yuichi Kanaoka's Special Issues, Vol. 59, No. 2, 2003
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■ Synthesis of (±)-Pinnaic Acid
Ichiro Hayakawa, Hirokazu Arimoto,* and Daisuke Uemura
*Graduate School of Science, Nagoya University, Chikusa, Nagoya, Aichi 464-8602, Japan
Abstract
(±)-Pinnaic acid (1) was synthesized via the catalytic hydrogenation of an α, β-unsaturated ketone (12) as the key step to construct an aza-spiro skeleton.
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■ Trimethylaluminum-promoted 1,4-Addition Reaction of Cuprates to Six or Eight-membered 2-Hydroxymethyl Enones
Khanitha Pudhom, Jun-ichi Matsuo, and Teruaki Mukaiyama*
*The Kitasato Institute, Center for Basic Research, 6-15-5 (TCI), Toshima, Kita-ku, Tokyo 114-0003, Japan
Abstract
1,4-Addition reaction of higher order cyanocuprates such as Ph2Cu(CN)Li2 and [Et3SiO(CH2)3C(=CH2)]2Cu(CN)Li2 (3) to six or eight-membered cyclic 2-hydroxymethyl enones proceeded efficiently by successive treatment with trimethylaluminum and cuprate reagents. A side chain for C-ring of 19-hydroxypaclitaxel (1) was introduced in high yields on treating highly functionalized eight-membered cyclic hydroxymethyl enone (2c) with trimethylaluminum and cuprate (3).
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■ A Facile and Direct Synthesis of Isoquinolone Derivatives from Allenes: Intramolecular Carbopalladation of Allenes Followed by Amidations
Kazuhiro Watanabe and Kunio Hiroi*
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
A new efficient synthesis of isoquinolone skeletons by nucleophilic substitution through intramolecular carbopalladation with the assistance of a catalytic amount of Pd(OAc)2 was developed. Palladium-catalyzed cyclization of (o-iodobenzamidoalkyl)allene compounds afforded the corresponding isoquinolone derivatives in good yields.
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■ Acid-catalyzed Photocycloaddition of 6-Chloro-1,3-Dimethyluracil to Polycyclic Aromatic Hydrocarbons
Kazue Ohkura, Shun Uchiyama, Masayuki Sato, James M. Diakur, and Koh-ichi Seki*
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
The acid-catalyzed photoreaction of 6-chloro-1,3-dimethyluracil (6-ClDMU) with various polycyclic arenes was investigated: UV-Irradiation of a solution of 6-ClDMU with phenanthrene (1a), 9-cyanophenanthrene (1b) and pyrene (1f) in cyclohexane effected 1,2-cycloaddition to furnish the corresponding cyclobutapyrimidines as the predominant adducts, while the substitution reaction with acenaphthene (1e) and chrysene (1g) proceeded to give the corresponding 6-aryl-1,3-dimethyluracils.
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■ A Synthetic Approach to Bengazoles: A Synthesis of Deacylbengazole
Pabba Chittari, Yasumasa Hamada, and Takayuki Shioiri*
*Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
The synthesis of deacylbengazole (3) and the C1-C9 fragments (4 and 5) of bengazoles was accomplished by use of the Thomas SnCl4-assisted coupling of the oxazole aldehydes with δ-alkoxyallylstannanes followed by the Sharpless asymmetric dihydroxylation as key steps.
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■ Synthesis of (3-Indolyl)heteroaromatics by Suzuki-Miyaura Coupling and Their Inhibitory Activity in Lipid Peroxidation
Atsushi Nishida,* Naoki Miyashita, Mihoko Fuwa, and Masako Nakagawa
*Graduate School of Pharmaceutical Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
A variety of (3-indolyl)heteroaromatic compounds were synthesized by Suzuki-Miyaura coupling of 3-indolylboronic acid and halogenated heteroaromatics. 2-(3-Indolyl)thiophene showed potent inhibitory activity against lipid peroxidation by rat liver microsome.
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■ First Synthesis of 4,6-Dialkyl-1,2,3- triazines via Dialkylcyclopropenones
Kiyoshi Matsumoto,* Tomasz Girek, Akihiro Okada, and Naoto Hayashi
*Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan
Abstract
2-Methyl-4,6-dialkyl-1,2,3-triazin-5(2H)-ones (12a-e) were prepared for the first time from the corresponding cyclopropenones that were prepared by Nakamura’s method.
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■ A New Efficient Synthesis of Both Enantiomers of Macrosphelide Core: A Potential Precursor for Functionalized Macrosphelides
Yuji Matsuya, Takanori Kawaguchi, Hideo Nemoto,* Hiroshi Nozaki, and Hiroki Hamada
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
The asymmetric synthesis of a macrosphelide core (1) and its enantiomer was achieved from (S)- or (R)-3-hydroxybutyrate in excellent yields. These compounds are potentially useful precursors for the preparation of biologically important macrosphelide analogues.
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■ A Stereocontrolled Synthesis of (+)-Rhopaloic Acid A Using a Dioxabicyclo[3.2.1]octane Chiral Building Block
Kohei Kadota and Kunio Ogasawara*
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Utilizing a chiral building block having a dioxabicyclo[3.2.1]octane framework, (+)-rhopaloic acid A, a potent cytotoxic norsesterterpene isolated from the marine sponge Rhopaloeides sp., has been synthesized in a stereocontrolled manner.
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■ A New Route to the Calcitriol A-Ring Precursor Using a Bicyclo[3.2.1]octane Chiral Building Block
Norio Miyazawa, Ayako Tosaka, Keisuke Hanada, and Kunio Ogasawara*
*Pharnaceutical Institute, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan
Abstract
A concise route to the A-ring precursor of calcitriol (1α,25-dihydroxyvitamin D3) has been developed starting from the chiral building block having a bicyclo[3.2.1]octane framework. Since we have already developed a diastereocontrolled synthesis of the C/D-ring precursor starting with the enantiomeric chiral building block, the present synthesis implies the total synthesis of calcitriol from a single precursor in a formal sense.
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■ Structure Determination of Lustromycin, an Antibiotic against Anaerobic Bacteria
Masaki Handa, Hideaki Ui, Daisuke Yamamoto, Soichi Monma, Yuzuru Iwai, Toshiaki Sunazuka, and Satoshi Omura*
*Kitasato Institute for Life Sciences, Kitasato University, and The Kitasato Institute, Shirokane, Tokyo 108-8642, Japan
Abstract
Extensive homo and heteronuclear two-dimensional NMR studies revealed lustromycin, an anti-anaerobic antibiotic. Its structure consists of a decaline ring system fused to a 10-membered macrolactone and a 14-membered macrolactone having an enol ether moiety conjugated with a maleic anhydride functionality.
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■ Hetero Diels-Alder Reaction Catalyzed by New Axially Dissymmetric Ligands with Fluorinated Chiral Centers
Masaaki Omote, Tomokuni Hasegawa, Kazuyuki Sato, Akira Ando, and Itsumaro Kumadaki*
*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan
Abstract
We have reported a new type of axially dissymmetric ligand, (R)-bis{(R)-2,2,2-trifluorohydroxyethyl}biphenyl ((R)-(R)2-1), which showed an excellent asymmetric induction in the reaction of Et2Zn to benzaldehyde. Now, a pentafluoroethyl analog of this ligand ((R)-(R)2-6) was synthesized. Both ligands were found to work as a ligand for an asymmetric hetero Diels-Alder reaction of benzaldehyde (2) with the Danishefsky's diene (4). Titanium or aluminum complexes of (R)-(R)2-1 or (R)-(R)2-6 catalyzed this asymmetric reaction moderately to give products of up to 54% ee.
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■ Cycloaddition of Naphthalenyl and Anthracenyl Imines: Interesting Aspects of the Staudinger Reaction
Indrani Banik, Linda Hackfeld, and Bimal K. Banik*
*Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, U.S.A.
Abstract
Cycloaddition of imines derived from naphthalene and anthracene derivatives under Staudinger reaction conditions proceeded exceedingly well with remarkable control of stereochemistry to the corresponding β-lactams.
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■ Direct and Stereoselective Construction of β-Mannosidic Linkages Capitalizing on 4,6-O-Benzylidene-protected D-Mannopyranosyl Diethyl Phosphite
Toshifumi Tsuda, Shinya Sato, Seiichi Nakamura, and Shunichi Hashimoto*
*Graduate School of Pharmaceutical Science, Hokkaido University, Sapporo 060-0812, Hokkaido
Abstract
A direct and practical method for the stereoselective construction of β-mannosidic linkages has been developed by using 2,3-di-O-benzyl-4,6-O-benzylidene-D-mannopyranosyl diethyl phosphite as a glycosyl donor and trimethylsilyl triflate as a promoter.
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■ Capture of Phenolic Endocrine Disruptors with 2-Pyridone
Ichiro Takahashi,* Masahiro Takahashi, Hidehiko Kitajima, Masami Wagi, Yumi Takahashi, Machiko Sabi, Minoru Hatanaka, Akihito Yamano, Tomihisa Ohta, and Shinzo Hosoi*
*Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910, Japan
Abstract
Crystalline molecular complexes between phenolic endocrine disruptors and 2-pyridones were prepared in fairly good isolated yields through simple procedures. Crystal structure of a complex between bisphenol A and 2-pyridone (1:1 molar ratio) is also described.
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■ Synthesis and CD Measurement of Chiral 1-Ethyl-3-carboxy-1,2,3,4-tetrahydro-β-carbolines: C1 Configuration and Second Sphere Chirality
Masashi Yokoya, Kyohei Masubuchi, Mariko Kitajima, Hiromitsu Takayama, and Norio Aimi*
*Graduate School of Pharmaceutical Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Chiral diastereomers, (1S)-ethyl-(3S)-carboxy-1,2,3,4-tetrahydro- β-carboline and (1R)-ethyl-(3S)-carboxy-1,2,3,4-tetrahydro-β-carboline, were synthesized. Complete 1H and 13C NMR spectral assignments were made and the C-ring conformations were clarified by NMR spectral measurements and DFT potential energy calculation using the 6-31G(d) basis set. CD spectra were measured and the 1Lb band Cotton effects were found to be controlled by both the C1 absolute configuration and the C-ring conformation.
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■ Total Synthesis of Lennoxamine and Chilenine via Ring-Expansion of Isoindoloisoquinoline to Isoindolobenzazepine
Yuji Koseki, Shinya Katsura, Shuichi Kusano, Harumi Sakata, Hiroto Sato, Yoshinori Monzene, and Tatsuo Nagasaka*
*Tokyo University of Pharmacy and Life Science, School of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Convenient synthesis of the benzazepine alkaloids, lennoxamine (1) and chilenine (2), is described. The key steps are conversion of methylenelactam (5) to an N-tertiary acyliminium ion precursor (16) and a novel expansion of the six-membered ring of 4 to a benzazepine ring system (3b), which could be transformed into lennoxamine (1) and chilenine (2).
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■ Concise Synthesis of Tetrahydrophenanthridone by Palladium Reagent
Takashi Harayama,* Hiroko Toko, Hiromi Nishioka, Hitoshi Abe, and Yasuo Takeuchi
*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
Heck reaction of N-(2-halophenyl)-N-methyl-1-cyclohexene-1-carboxamide (1) and 2-bromo-N-methyl-N-phenyl-1-cyclohexene-1-carboxamide (4) using a palladium reagent under several reaction conditions was examined. Reaction of 4 using Pd(OAc)2, DPPP, and Bu3P afforded tetrahydrophenanthridone (5) in excellent yield.
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■ Synthesis of Ketosyl Spiro-isoxazolidine by 1,3-Dipolar Cycloaddition of 1-Methylenesugars with Nitrones —A New Access to C-Glycosyl Amino Acids
Xiaoliu Li, Hideyo Takahashi, Hiro Ohtake, and Shiro Ikegami*
*School of Pharmaceutical Sciences, Teikyo University, 1091-1, Sagamiko, Kanagawa 199-0195, Japan
Abstract
The 1,3-dipolar cycloaddition reactions of 1-methylenesugars (1a~c) with nitrones (2 and 5) were carried out diastereoselectively under the catalysis of BF3·Et2O at low temperature and afforded the α-stereoselective spiro ketosyl isoxazolidines in good to excellent yields. The reductive isoxazolidine ring-opening of the spiro moiety with the treatment of zinc and acetic acid resulted in a new kind of C-glycosyl amino acid possessing a ketose form, providing an access to C-glycosyl amino acids. The structures of the synthesized compounds were confirmed by the spectroscopic analyses.
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■ Investigation of the Ring-opening Cross-Metathesis Reaction of 2-Azabicyclo[2.2.1]hept-5-en-3-one (ABH) with Allylsilanes
Minoru Ishikura,* Makoto Saijo, and Ayako Hino
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
An examination of the ring-opening cross-metathesis reaction of N-substituted 2-azabicyclo[2.2.1]hept-5-en-3-ones (ABH) (1) with allylsilanes (2) in the presence of ruthenium catalysts was undertaken.
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■ Synthesis and Character of New Bis(isoxazoline) Ligands
Toshio Shinohara, Kazuhiko Wakita, Midori A. Arai, Takayoshi Arai, and Hiroaki Sasai*
*The Institute of Scientific and Industrial Research, Osaka University, 8-1. Mihogaoka, Ibaraki, Osaka 567-0047, Japan
Abstract
Synthesis of two kinds of new bis(isoxazoline) ligand, achiral 2,2’-bis(isoxazolinyl)propane and (R)-2,2’-bis(isoxazolinyl)-1,1’-binaphthyl bearing an axial chirality is described. Both of the bis(isoxazoline) ligands accelerated the Pd(II)-catalyzed Wacker-type cyclization of alkenyl alcohol. The isoxazoline ligands were found to be essential to promote the cyclization.
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■ Stereoselective Synthesis of the Optically Pure AB-Ring Moiety of Trichothecene Sesquiterpene (+)-Calonectrin
Akira Iida, Kazuhide Konishi, Hironobu Matsumoto, Masafumi Kaneko, and Kiyoshi Tomioka*
*Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
The optically pure trichothecene cis-AB ring moiety (1) was synthesized starting from an optically pure butenolide (7) through the ring closing olefin metathesis for the formation of the A-ring and a Lewis acid mediated cyclization to the cis-fused tetrahedrochromane skeleton that had been converted to natural trichothecene, (+)-calonectrin.
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■ Rhodium-catalyzed Asymmetric 1,4-Addition of 3-Thiopheneboronic Acid to α,β-Unsaturated Carbonyl Compounds
Kazuhiro Yoshida and Tamio Hayashi*
*Department of Chemistry, Gradauate Schol of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Abstract
Asymmetric 1,4-addition of 3-thiopheneboronic acid to α,β-unsaturated carbonyl compounds proceeded with high enantioselectivity in the presence of 3 mol% (Rh) of [Rh(OH)((S)-binap)]2 in dioxane/H2O (10/1) at 40 °C to give the corresponding optically active β-(3-thienyl) carbonyl compounds of over 94% ee.
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■ Photochemical Identification of the Binding Region for (S)-Semotiadil on Sodium Channels: Comparison with that for (R)-Semotiadil on Skeletal Muscle Calcium Channel
Hiromi Yoshikawa, Eisuke Shimizu, Kohichi Kawahara, Akihiko Kuniyasu, Toshiro Shibano, and Hitoshi Nakayama*
*Department of Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
To clarify the recognition site of (S)-semotiadil in the Na+ channels, we employed photoaffinity labeling with (S)-[3H]-D51-4700, an azidophenyl derivative of (S)-semotiadil, to Na+ channel preparations from rat brains and porcine hearts, and the results were compared with those by (R)-enantiomer to skeletal muscle Ca2+ channel. Protease-digestion of the photolabeled Na+ channels followed by quantitative immunoprecipitation assay using a site-directed antibody, revealed that 10- and 13- kDa fargments of brain and cardiac Na+ channels, respectively, were located within the regions including IVS6. These regions are corresponding to the 8.3 kDa fragment photolabled by (R)-[3H]-D51-4700 in the skeletal muscle Ca2+ channel. Interestingly, however, the photoincorporation of (S)-[3H]-D51-4700 into the Na+ channel was 2-3 times higher than that of (R)-isomer; and visa versa in the Ca2+ channels.
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■ Synthesis of the Amide Analog of Alternariolide (AM-Toxin I), a Host Specific Phytotoxin for Apple Leaves
Mitsuru Sakai, Toshikatsu Okuno, Kimiko Hashimoto,* and Haruhisa Shirahama*
*School of Science, Kwansei Gakuin University, 1-1-155 Uegahara, Nishinomiya 662-8501, Japan
Abstract
The amide analog of alternariolide (AM-toxin I) was synthesized with high efficiency. The analog showed comparable biological activity to that of alternariolide.
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■ A New Chiral Pyrrolidine- and Pyrrolidinoneethanols for Enantioselective Addition of Diethylzinc to Arylaldehydes
Yuko Okuyama, Hiroto Nakano,* Mayumi Igarashi, Chizuko Kabuto, and Hiroshi Hongo
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
New chiral pyrrolidineethanols and unusual type of pyrrolidinoneethanol fused bicyclo[2.2.2]octane ring systems as backbones were synthesized and were used to the addition of diethylzinc to aromatic aldehydes to afford the secondary aryl alcohols leading to enantioselectivities up to 94% ee.
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■ Structures of Two New Highly Oxygenated Labdane-Type Diterpenoids and a New Cadinane-Type Sesquiterpenoid Possessing a Cyclic Ether Linkage from the Liverwort Ptychanthus striatus
Toshihiro Hashimoto, Shigeru Takaoka, Masami Tanaka, and Yoshinori Asakawa*
*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-machi, Tokushima, 770-8514, Japan
Abstract
As a part of our systematic investigation of biologically active substances of liverworts, we studied the chemical constituents of the liverwort Ptychanthus striatus belonging to the Lejeuneaceae family, and isolated two novel labdane-type diterpenoids, named ptychantins J and K, and a new cadinane-type sesquiterpene possessing a cyclic ether linkage. Their relative structures were determined by a combination of high resolution NMR spectrometry, X-Ray crystallographic analysis and chemical degradations.
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■ Nitrogen Fixation Using Titanium Complex: Reinvestigation of the Reaction Conditions
Masaya Akashi and Miwako Mori*
*Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
The amounts of Li and TMSCl of a TiX4-Li-TMSCl system for a nitrogen fixation method, previously reported by our group, were examined. As the results, the reactivity of titanium-nitrogen complexes prepared from 4 equiv. of Li and 6 equiv. of TMSCl for Ti(OPr-i)4 (1 equiv.) under an atmosphere of nitrogen was same as that of titanium-nitrogen complexes reported previously.
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■ The Photodecarboxylative Addition of Carboxylates to Phthalimides: Scope and Limitations
Michael Oelgemöller, Peter Cygon, Johann Lex, and Axel G. Griesbeck*
*Institute of Organic Chemistry, University of Cologne, Greinstrasse 4, D-50939 Köln, Germany
Abstract
Intermolecular photoinduced decarboxylative additions of a series of alkylcarboxylates to N-substituted phthalimides gave the corresponding hydroxy-phthalimidines in moderate to high yields of 39-89%. The potassium salt of 1- adamantanecarboxylic acid predominately underwent simple decarboxylation when irradiated in the presence of N-methylphthalimide. In case of phthalimides carrying suitable leaving groups within the N-side chain, decarboxylation, retro-Aldol cleavage or decarbonylation preceded the intermolecular addition step.
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■ Preparation of 7-Substituted 4,5-Dihydro-7H-Pyrano[3,4-c]isoxazole Derivatives
Koji Yamada, Fumio Yamada, and Masanori Somei*
*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
An easy approach to 7-substituted 4,5-dihydro-7H-pyrano[3,4-c]isoxazole derivatives (3a-b and 6a-d) is described by the reaction of 2-aryl substituted 1-nitro-3-oxa-6-heptynes (2, 5a and 5b) with n-BuLi, followed by treatment with acetic anhydride.