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
Satoshi Omura's Special Issues, Vol. 69, No. 1, 2006
Published online: 22nd August, 2006
■ Addition Reaction of o-Toluamides with Chiral Auxiliary Derived from 2-Amino-1,3-propanediols to Imines
Maria Chrzanowska* and Agnieszka Dreas
*Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland
Abstract
Stereoselectivity of the addition reaction of o-toluamides, incorporating 2-amino-1,3-propanediols as chiral auxiliary to imines has been studied. Addition products, diastereomerically enriched, after column chromatography separation were obtained and further transformed to (S)-(-)-or (R)-(+)-8-oxoberbines with ee up to 97%.
Published online: 10th October, 2006
■ Synthesis, Oxygen Activation, and DNA-Cleaving Property of a Histidine-Pyridine-Histidine Ligand
Masahiro Matsumoto, Yoshinori Okuno, Yukiko Ogata, Hiromasa Kurosaki, Yoshinari Okamoto, and Masami Otsuka*
*Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
Abstract
A novel metal-chelating system comprising a 4-dimethylaminopyridine and two histidine appendages was synthesized. The two histidines were introduced by different manners; one through an amide linkage and other via a secondary amino linkage. ESR spectrum suggested a distorted pentacoordinate configuration of the copper complex of the ligand. The iron complex of the ligand had oxygen-activating property as shown by ESR spin trapping and DNA-cleaving activity as evaluated by experiments using pUC19 DNA.
Published online: 18th August, 2006
■ Transformations of 4-Hydroxy-5,6,7,8-tetrafluorocoumarin Derivatives with Monoamines
Konstantin V. Shcherbakov, Yanina V. Burgart, Victor I. Saloutin,* and Oleg N. Chupakhin
*Institute of Organic Synthesis of Urals Division of Russian Academy of Sciences, 22/20, S. Kovalevskoy/Akademicheskaya Str., Ekaterinburg, GSP-147, Russia
Abstract
The 4-hydroxy-5,6,7,8-tetrafluorocoumarin reacts with the monoamines to form salts under the mild conditions or the 4-alkyl(aryl)aminocoumarins on refluxing in o-xylene. The 3-acetyl-4-hydroxy- 5,6,7,8-tetrafluorocoumarin reacts with the strong basic amines in the polar solvents to give salts that can be transformed into the 3-alkylaminoethylidene-5,6,7,8-tetrafluorobenzopyran-2,4-diones. The latter can be obtained by reaction of the 3-acetylcoumarin with different amines. The reactions of the 3-acetylcoumarin with the strong basic amines in dimethyl sulfoxide lead to the 7-alkylamino-3-alkylaminoethylidene-5,6,8- triflurobenzopyrandiones. The 3-acetimidoyl-4-hydroxy-5,6,7,8-tetrafluorocoumarin affords the 3-alkylaminoethylidenebenzopyrandiones with the monoamines, but in dimethyl sulfoxide the 7-substituted 3-acetimidoyl- 5,6,8-trifluorobenzopyrandiones or the 7-alkylamino-3-alkylaminoethylidene- 5,6,8-triflurobenzopyrandiones can be obtained.
Published online: 25th August, 2006
■ Efficient Synthesis of Optically Active 4,5-Dihydroxy-2,3,4,5-tetrahydro-1H-1-benzazepine Derivatives Utilizing Lipase-Catalyzed Transesterification
Tadaaki Ohtani,* Kazuyoshi Kitano, Jun Matsubara, Yoshikazu Kawano, Makoto Komatsu, Minoru Uchida, Fujio Tabusa, and Yoshimitsu Nagao
*Medicinal Chemistry Research Institute, Otsuka Pharmaceutical Co., Ltd., Kagasuno 463-10 Kawauchi-cho, Tokushima 771-0192, Japan
Abstract
As an efficient and enantioselective synthesis of the 4,5-dihydroxy- benzazepine compounds, the syntheses of optically active 5-O-protected trans- 4,5-dihydroxybenzazepine derivatives were accomplished. The trans-7-chloro- 4-hydroxy-5-methoxymethoxy-1-(p-toluenesulfonyl)-2,3,4,5-tetrahydro-1H-1- benzazepine [(±)-4] was kinetically resolved by lipase-catalyzed trans- esterification. The optically active 4* was isomerized into the cis compound (6*) utilizing the Mitsunobu esterification followed by hydrolysis. The chiral compounds (4* and 6*) were converted to the 4,5-bismethoxymethoxy compounds (7*-10*), which were the intermediates for the compounds (2a, b and 3a, b).
Published online: 26th September, 2006
■ Strained 1-Azabicyclo[1.1.0]butanes in the Synthesis of Azetidinethiocarboxylate Derivatives
Marta Woznicka, Katarzyna Urbaniak, Grzegorz Mloston,* and Heinz Heimgartner*
*Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Abstract
The reaction of 3-phenyl-1-azabicyclo[1.1.0]butane (1a) with chlorodithio-formates (5) at room temperature yielded 3-chloro-3-phenylazetidine-1-carbodithioates (6). The same products were obtained in a two-step procedure by treatment of 1a with thiophosgene to give azetidine-1-carbothioyl chloride (7a), followed by treatment with the corresponding sulfane. 3-Chloro-3-phenylazetidine-1-thiocarbamides (8) and the corresponding O-methyl 1-carbothioates (9) were prepared by the reaction of compounds (7) with amines and methanol, respectively. These reactions open a new access to derivatives of azetidine-1-carboxylic acid.
Published online: 10th October, 2006
■ Synthesis and Properties of Novel Bis(1,3-benzodithiolium)-Type Dications Containing a Biaryl Unit: New Redox Systems Undergoing Reversible Structural Changes by Electron Transfer
Akira Ohta,* Chihiro Ueki, Yuzuru Uchiyama, and Kunihide Fujimori*
*Department of Chemistry, Faculty of Science, Shinshu University, Asahi, Matsumoto 390-8621, Japan
Abstract
In order to develop new redox systems which undergo reversible structural changes by electron transfer, bis(1,3-benzodithiolium)-type dications (52+) containing a biaryl unit have been synthesized by hydride abstraction of the corresponding bis(1,3-benzodithiol-2-yl)biaryls (8). Reduction of 52+ with zinc gave the corresponding intramolecular cyclization products (6), which reverted to 52+ by oxidation. Cyclic voltammetry also showed the efficient interconversion between both states. X-Ray analyses revealed that the twist angle of the biaryl unit decreases largely by reductive intramolecular cyclization.
Published online: 20th October, 2006
■ Inhibition of NF-Kappa B Activation by 9-Methylstreptimidone Isolated from Streptomyces
ZhiChao Wang, Masayuki Igarashi, Yoko Ikeda, Ryouichi Horie, and Kazuo Umezawa*
*Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan
Abstract
In the course of our screening of NF-κB inhibitors from microbial secondary metabolites, we isolated a piperidine compound, 9-methylstreptimidone, from the culture filtrate of Streptomyces. 9-Methylstreptimidone inhibited LPS-induced NO production and NF-κB-induced transcriptional activity. It showed selective toxicity on adult T-cell leukemia cells in which NF-κB is constitutively activated. Unlike cycloheximide it did not inhibit protein synthesis.
Published online: 17th October, 2006
■ Catalytic, Stereoselective Glycosylation - Spiroketalization of 3,4,5-Tri-O-benzyl-β-D-fructopyranose Generating Di-D-fructopyranose- 1,2’:2,1’-dianhydride
Eisuke Kaji,* Reiko Saiga, Emiko Kurimoto, and Takashi Nishino
*School of Pharmaceutical Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan
Abstract
α-D-Fructopyranose β-D-fructopyranose-1,2’:2,1’- dianhydride has been stereoselectively synthesized by tandem catalytic glycosylation-spiroketalization of 3,4,5-tri-O-benzyl-β-D-fructo- pyranose. Of the several protic acid catalysts which exist, 0.3 molar equivalent trifluoromethane sulfonic acid in toluene was found to be most effective to afford the dianhydride in good yield.
Published online: 31st October, 2006
■ Synthesis and Biological Activities of Biscarboxymethyl Lipid A Analogues
Mikayo Kataoka, Masaya Hashimoto, Yasuo Suda, Shoichi Kusumoto, and Koichi Fukase*
*Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, Japan
Abstract
Biscarboxymethyl analogues of Escherichia coli lipid A and the biosynthetic precursor-type lipid A were synthesized in order to elucidate the role of the acidic functional groups in the biological activity. Both analogues showed respective activities similar to those of their natural counterparts, i. e., the hexaacyl E. coli lipid A analogue showed potent immunostimulating activity, whereas the tetraacylated biosynthetic precursor-type lipid A analogue showed the antagonistic activity. The present study clearly indicates that the acidic functional groups but not phosphate groups are essential for the expression of the biological activities.
Published online: 31st October, 2006
■ Hetero Diels-Alder Type Reactions Between Danishefsky’s Dienes in the Presence of Lewis Base Catalysts.
An Efficient Method for the Synthesis of Substituted 2,3-Dihydropyran-4-ones
Takayuki Kitazawa and Teruaki Mukaiyama*
*Center for Basic Research, The Kitasato Institute, 6-15-5 (TCI), Toshima, Kita-ku, Tokyo 114-0003, Japan
Abstract
Alkoxy anion such as methoxide anion works effectively as Lewis base catalyst to activate silicon-carbon bond of 1-methoxy-3-trimethylsilyloxy-1,3-butadiens (Danishefsky’s dienes) in the reaction between aldehydes and ketones. By using Lewis base as catalyst, acid sensitive substrates and Lewis basic moiety containing substrates can be used in this reaction. The hetero Diels-Alder type reaction proceeds through stepwise mechanism between silyl enolates and carbonyl compounds.
Published online: 6th July, 2006
■ Oxidative Cyclization Reaction of Dibenzylbutanolides with Combined Utilization of Synthetic Chemistry and Biotechnological Methods
Masumi Takemoto,* Yoko Hongo, Youichi Aoshima, and James Peter Kutney
*School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, 422-8526, Japan
Abstract
We reported plant cell culture (as an enzyme source)-catalyzed oxidative cyclization reaction of dibenzylbutanolides (1a, b, d, e) to cyclic product (2a, b, d, e) via a hypothetical quinone methide intermediate.
Published online: 11th July, 2006
■ Synthesis of the 37-epi-HIJ Ring System of Adriatoxin
Naoki Hiramatsu and Yuji Mori*
*Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan
Abstract
A stereoselective synthesis of the 37-epi-HIJ ring system of adriatoxin, a diarrheic shellfish toxin of mussels, was achieved. The present synthesis involves installation of the tertiary alcohol structure of the I ring via a spiro-epoxide and subsequent formation of the J ring dihydropyran followed by the stereoselective oxidation of an enolic double bond and sulfation of an anomeric hydroxy group.A stereoselective synthesis of the 37-epi-HIJ ring system of adriatoxin, a diarrheic shellfish toxin of mussels, was achieved. The present synthesis involves installation of the tertiary alcohol structure of the I ring via a spiro-epoxide and subsequent formation of the J ring dihydropyran followed by the stereoselective oxidation of an enolic double bond and sulfation of an anomeric hydroxy group.
Published online: 21st July, 2006
■ Four New Kabiramides from the Thai Sponge, Pachastrissa nux
Chutima Petchprayoon, Yumiko Asato, Tatsuo Higa, Luis F. Garcia-Fernandez, Suwigarn Pedpradab, Gerard Marriott, Khanit Suwanborirux,* and Junichi Tanaka*
*Department of Chemistry, Biology, and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan
Abstract
Four new cytotoxic kabiramides (1-4) together with the known kabiramides B, C, and D have been isolated from the sponge Pachastrissa nux collected in the Gulf of Thailand. The structures of the new entities were elucidated by spectroscopic methods. Kabiramide C derivatives (8-11) were prepared and evaluated for cytotoxicity together with the natural congeners.
Published online: 6th July, 2006
■ Synthesis of the Hemiacetal Pheromone of the Spined Citrus Bug Biprorulus bibax Utilizing an Iridium Catalyzed Oxidative Lactonization
Takeyuki Suzuki,* Kenji Morita, Hisako Ikemiyagi, Kazuhiro Watanabe, Kunio Hiroi, and Tadashi Katoh
*The Institute of Scientific and Industrial Research (ISIR), Osaka University, Mihogaoka, Ibaraki, Osaka 567-0047, Japan
Abstract
cis-3,4-bis[(E)-1-butenyl]tetrahydro-2-furanol, the pheromone of the Biprorulus bibax, was synthesized by the iridium catalyzed oxidative lactonization.
Published online: 11th August, 2006
■ Tryptophan 4-Aminocinnamamides from a Myxomycete Fuligo aurea
Takahiro Hosoya, Yui Kato, Yukinori Yamamoto, Masahiko Hayashi, Kanki Komiyama, and Masami Ishibashi*
*Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
Abstract
Two new tryptophan derivatives, cis- and trans- tryptophan 4-aminocinnamamides (1 and 2), were isolated from field-collected fruit bodies of a myxomycete Fuligo aurea, along with a hexacyclic triterpenoid, chamaecydin (3), previously known as a plant constitutent. The structures of these compounds were elucidated on the basis of spectroscopic data.
Published online: 18th August, 2006
■ Lycovatine A, a C16N-Type Quaternary Alkaloid from Lycopodium clavatum var. robustum
Takaaki Kubota, Tomoe Sunaura, Hiroshi Morita, Yuzuru Mikami, Tomohiro Hoshino, Yutaro Obara, Norimichi Nakahata, and Jun’ichi Kobayashi*
*Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
A new C16N-type quaternary alkaloid, lycovatine A (1), has been isolated from the club moss Lycopodium clavatum var. robustum, and the structure including the relative stereochemistry was elucidated on the basis of spectroscopic data.
Published online: 11th August, 2006
■ Synthesis of 2-Hydroxy-1,2,3,4-tetrahydroquinoline Derivatives by a Cyclocondensation Reaction
Giuseppe Cremonesi, Piero Dalla Croce, Francesco Fontana, and Concetta La Rosa
*Department of Organic and Industrial Chemistry, C.N.R.-I.S.T.M., Via Venezian 21, I-20133 Milano, Italy
Abstract
The reaction of enolates (2) of 1,3-dicarbonyl compounds with N-(2-bromomethylphenyl)benzenesulfonamides (1) gives N-phenylsulfonyl-2-hydroxy-1,2,3,4-tetrahydroquinoline derivatives (3) whose structure and stereochemistry were assigned on the basis of analytical and spectroscopic data. Some studies on the chemical behaviour of 3 are also reported.
Published online: 12th September, 2006
■ New Furanocoumarins Isolated from the Roots of Ferulago isaurica Pesmen Growing in Turkey
Ceyda Sibel (Erdurak) Kilic, Yoshihito Okada, Maksut Coskun, and Toru Okuyama*
*Meiji Pharmaceutical University, DepartmentÅ@ofÅ@NaturalÅ@Medicine & Phytochemistry, 2-522-1Å@Noshio, Kiyose-shi, Tokyo 204-8588, Japan
Abstract
New furanocoumarins, 4’-O-benzoyl rutaretin (1) and 4’-O-3-methyl-2-butenoyl rutaretin (2) along with five known coumarins, felamedin (3), prantschimgin (4), bergapten (5), xanthotoxin (6) and isoimperatorin (7), have been isolated from the chloroform extract of the roots of Ferulago isaurica Pesmen. These structures have been elucidated on the basis of spectral and physical methods.
Published online: 22nd August, 2006
■ Synthesis and Biological Activities of Sugar Analogs of Mycalamide A
Shunya Takahashi, Akihiro Okada, Miho Nishiwaki, and Tadashi Nakata*
*Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Abstract
Several new artificial sugar analogs (3-6) of mycalamide A (1), a potent antiviral and antitumor agent, were synthesized through a coupling reaction of glycosyl amines (10), (11), (15), and (16) with pederic acid (12), and their cytotoxity and antiviral activity were tested.
Published online: 28th July, 2006
■ Short Step Synthesis of Natural 2-Arylquinolones Based on Iridium-Catalyzed Three-Component Coupling Quinoline Synthesis
Takayuki Nakajima, Takashi Inada, and Isao Shimizu*
*Department of Applied Chemistry, Graduate School of Science and Engineering, Waseda University, Okubo 3-4-1, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
Eduline (1a), graveoline (1b), and 6-methoxy-2-(4-methoxyphenyl)-1-methylquinolone (1c) were synthesized by iridium-catalyzed three-component coupling reaction. Reaction of an aniline, an aromatic aldehyde, and acetaldehyde gave the corresponding substituted quinoline. Using 1,1-dimethoxyethane instead of acetaldehyde, the three component coupling reactions were also carried out to give the quinolines in higher yields. N-Methylation of the quinolines with methyl trifrate followed by oxidation with potassium ferricianate gave the quinolones.
Published online: 8th September, 2006
■ Design and Synthesis of Telomestatin Derivatives and Their Inhibitory Activity of Telomerase
Masayuki Tera, Yoshihiro Sohtome, Hiromichi Ishizuka, Takayuki Doi, Motoki Takagi, Kazuo Shin-ya,* and Kazuo Nagasawa*
*Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Abstract
Telomestatin derivatives of 2a-2c, which have macrocyclic bisamide structure, were designed and synthesized. One of these compounds (2a) showed inhibitory activity of telomerase with an IC50 of 2 μM.
Published online: 18th August, 2006
■ Synthesis of N1,N3-Free Pyrimidine Bridged Polycyclic Compounds via Photo-Diels-Alder Reaction of N,N-Diacetyl-5-fluorouracil with Naphthalenes
Kazue Ohkura,* Tetsuya Ishihara, Ken-ichi Nishijima, James M. Diakur, and Koh-ichi Seki*
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
UV-Irradiation of 1,3-diacetyl-5-fluorouracil and naphthalene initiated the photo-Diels-Alder reaction to give the corresponding 1,4-adduct. Removal of the acetyl groups at N1 and N3 through hydrolysis afforded N1 and N3 unprotected ethenobenzoquinazoline in fair yield.
Published online: 22nd September, 2006
■ Neurotrophic Sesterterpenes Isolated from a Marine Sponge, Spongia sp.
Takanori Tokue, Shunsuke Miura, Hikaru Kato, Hiroshi Hirota, Tomihisa Ohta, and Sachiko Tsukamoto*
*Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan
Abstract
The MeOH extract of a marine sponge of the genus Spongia showed neurotrophic activity in pheochromocytoma (PC-12) cells. Purification of the extract afforded a new sesterterpene, deacetoxyscalarin (1), along with five known sesterterpenes (2-6). Among them, 2-6 induced neurite outgrowth in PC-12 cells at the concentration of 50 μg/mL but 1 was inactive.
Published online: 10th October, 2006
■ Enantioselective Intramolecular C-H Amidation of Sulfamate Esters Catalyzed by Chiral Dirhodium(II) Carboxylates
Minoru Yamawaki, Shinji Kitagaki, Masahiro Anada, and Shunichi Hashimoto*
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
The chiral dirhodium(II) carboxylate-catalyzed enantioselective intramolecular C-H amidation reaction of sulfamate esters via in situ generated iminoiodinanes is described. The use of dirhodium(II) tetrakis[N-tetrafluorophthaloyl-(S)-tert-leucinate], Rh2(S-TFPTTL)4, as a catalyst and PhI(OAc)2 as an oxidant provides cyclic sulfamidates in up to 48% ee.
Published online: 18th August, 2006
■ Norepinephrine Reuptake Inhibitors for Depression, ADHD and Other Neuropsychiatric Disorders
Ruppa P. Kamalesh Babu and Samarendra N. Maiti*
*Naeja Pharmaceutical Inc., 4260-91A St., Edmonton, AB, CANADA T6E 5V2, Canada
Abstract
Neuropsychiatric disorders have been actively studied for several decades. Many of these disorders were treated by pharmacotherapy, certain forms of psychotherapy, and electroconvulsive therapy. Several classes of drugs with a range of binding selectivities have been discovered and used in the treatment of various central nervous system (CNS) disorders. The earlier drugs had undesired side effects because of their binding to a broad range of neurotransmitters. However, with the advancement of science, there is an increasing understanding of the role of monoamine neurotransmitters in various CNS disorders, which had resulted in the rational design of potent drugs with very selective binding properties. Yet, there are many unanswered questions, and the CNS research is being more actively pursued than ever with newer additional tools such as magnetic resonance imaging (MRI), molecular imaging by positron emission tomography (PET), single-photon emission tomography (SPECT), etc. The goal of this review is to bring together the recent discoveries on selective norepinephrine reuptake inhibitors, developments, and their uses in depression and ADHD. Some of the dual inhibitors of norepinephrine and serotonin transporters have also been included in this review, as these have very similar applications.
Published online: 12th September, 2006
■ Synthesis of Partially Fluorinated Heterocycles from 4,4-Bis(trifluoromethyl) Substituted Hetero-1,3-dienes via C-F Bond Activation and Their Application as Trifluoromethyl Substituted Building Blocks
Klaus Burger,* Lothar Hennig, Jan Spengler, and Fernando Albericio
*Department of Organic Chemistry, University of Leipzig, Johannisallee 29, 04103 Leipzig, Germany
Abstract
Bis(trifluoromethyl) substituted hetero-1,3-dienes can be transformed into partially fluorinated five-membered heterocycles by a new reductive cyclization protocol. Certain members of the new class of heterocycles represent versatile building blocks. α-Trifluoromethyl α-amino acids, trifluoromethyl substituted butenolides and α-trifluoromethyl-γ-keto acids are readily available via 5-fluoro-4-trifluoromethyloxazoles and 2-fluoro-3-trifluoromethylfurans, respectively.
Published online: 18th August, 2006
■ Fluorine-Containing 2-Functionalized 1,3-Dicarbonyl Compounds for Heterocyclic Synthesis
Yanina V. Burgart, Victor I. Saloutin,* and Oleg N. Chupakhin
*Institute of Organic Synthesis of Urals Division of Russian Academy of Sciences, 22/20, S. Kovalevskoy/Akademicheskaya Str., Ekaterinburg, GSP-147, Russia
Abstract
Data on the synthesis and chemical transformations of 2-functionalized fluoroalkyl-containing 1,3-dicarbonyl compounds are reviewed. Reactions giving fluorinated heterocycles are discussed. The heterocyclization of non-substituted fluoroalkylated 1,3-dicarbonyl compounds with the same dinucleopiles is considered for the sake of comparison.