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
30th Anniversary's Special Issues, Vol. 61, No. 1, 2003
Published online: 24th June, 2003
■ Chemical Constituents of Pterocaulon redolens
Mayuree Kanlayavattanakul, Nijsiri Ruangrungsi,* Toshiko Watanabe, and Tsutomu Ishikawa
*Graduate School of Pharmaceutical Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Studies on the chemical constituents of the aerial parts of Pterocaulon redolens (Forst.f) F. Vill.(Asteraceae) resulted in the isolation of ten components: seven coumarins [5-methoxy-6,7-methylenedioxycoumarin (1), ayapin (2), puberulin (3), 5-methoxyscopoletin (4), 2’,3’-dihydroxypuberulin (5), isofraxidin (6), and 5-(2’,3’-dihydroxy-3’-methylbutyloxy)-6,7-methylenedioxycoumarin (7)] and three flavonoids [luteolin (8), tomentin (9), and chrysosplenol C (10)], among which 5 was firstly isolated as a natural product. The full 1H- and 13C-NMR spectral assignments for the isolated products, including revision of previous assignment in the literature are reported. Six coumarins (1-4, 6, and 7) and one flavonoid (8) displayed mild activity against Mycobacterium tuberculosis H37Ra. In addition, flavonoid (10) was firstly found to possess moderate cytotoxicity against breast cancer (BC) and human small cell lung cancer (NCI-H187) cell lines.
Published online: 24th June, 2003
■ Two New Xenicane Diterpenoids from Okinawan Soft Coral of the Genus, Xenia
Hiroaki Miyaoka, Masakazu Nakano, Kazuo Iguchi, and Yasuji Yamada*
*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Two new xenicane diterpenoids, dihydroxeniolide-A and isoxeniatriacetate, were isolated from Okinawan soft coral of the genus, Xenia. The relative configurations of two new xenicane diterpenoids were determined based on spectroscopic analysis. The absolute configuration of dihydroxeniolide-A was determined using the modified Mosher’s method. The absolute configuration of isoxeniatriacetate was determined by chemical conversion.
Published online: 4th August, 2003
■ Transformations of Alykl (5-Oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)acetates into 5-Heteroaryl-3-oxo-2-phenyl-3,5-dihydro-2H-pyrazolo[4,3-c]pyridine-7-carboxylates
David Bevk, Renata Jakse, Jurij Svete,* Amalija Golobic, Ljubo Golic, and Branko Stanovnik*
*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, 1000 Ljubljana, Slovenia
Abstract
Alkyl [(Z)-4-dimethylaminomethylidene-5-oxo-1-phenyl-4,5-dihydro- 1H-pyrazol-3-yl]acetate (4) was transformed with N- and C-nucleophiles into alkyl [4-(substituted amino)methylidene-4,5-dihydro-1H-pyrazol-3-yl]acetates (7) and alkyl (4-heteroarylmethylidene-4,5-dihydro-1H-pyrazol-3-yl)acetates (8), respectively. Compounds (7) cyclize by heating with DMFDMA in DMF into 2H- pyrazolo[4,3—c]pyridine-7-carboxylates (9).
Published online: 4th August, 2003
■ The Vilsmeier-Haack Reaction on Methyl Homologues of N-Benzyltetrahydrocarbazole (Synthetic Studies on Indoles 52)
Yasuoki Murakami,* Akira Ishii, Hidehiko Ozawa, Hiroko Okahira, Keiko Hosokawa, Tomiko Tashiro, Jin-ichi Muto, Hideharu Suzuki, Masanobu Tani, and Yuusaku Yokoyama
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
To examine the steric effect in the Vilsmeier-Haack reaction of N-benzyl-1,2,3,4-tetrahydrocarbazole (1), the reactions were carried out on three methyl homologues of 1. It was found that 1-methyl- or 4,4-dimethyl group has a large effect on reactivity due to their steric bulkiness. This result shows the importance of an initial attack at the 4a-position for the formation of these products.
Published online: 15th July, 2003
■ Generation and Reactions of 3-Phenyl-7,8-dehydro-1-azaazulene
Noritaka Abe,* Masao Yoshitsugu, Hiroyuki Fujii, and Akikazu Kakehi
*Department of Chemistry, Faculty of Science, Yamaguchi University, Yamaguchi 753-8512, Japan
Abstract
3-Phenyl-7,8-dehydro-1-azaazulenes were generated by the treatment of 8-bromo-3-phenyl-1-azaazulenes with potassium t-butoxide in DMSO or in THF in the presence of 16-crown-8-ether, and trapped with diphenylisobenzofuran as 3,7,12-triphenyl-1-aza-7,12-epoxynaphth[2,3-e]azulenes. The structure of the adduct, 2-bromo-3,7,12-triphenyl-1-aza-7,12-epoxynaphth[2,3-e]azulene, was deduced by X-Ray structure analysis. Similar treatment of 8-bromo-3-phenyl-1-azaazulene with potassium t-butoxide in the presence of furan gave 3-phenyl-1-aza-7,12-epoxynaphth[2,3-e]azulene and 7-phenyl-3H-3a,3c-dihydro-1-aza-3-oxacyclopenta[3,4]cyclobuta[1,2-e]azulene as cycloadducts.
Published online: 11th August, 2003
■ Synthesis of 3-Methylenepyrrolidines by Palladium-catalyzed [3+2] Cycloaddition of Alkylidenecyclopropanes with Imines
Byoung Ho Oh, Itaru Nakamura, Shinichi Saito, and Yoshinori Yamamoto*
*Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Abstract
Alkylidenecyclopropanes react with N-tosylimines in toluene in the presence of a catalytic amount of Pd(PPh3)4 and triphenylphosphine oxide to afford the corresponding [3+2] cycloaddition products, pyrrolidine derivatives, in good to excellent yields.
Published online: 4th August, 2003
■ Hexafluoroacetone as Protecting and Activating Reagent: An Efficient Strategy for Activation of Pyroglutamic Acid and Homologues
Ksenia Pumpor, Christoph Böttcher, Susanna Fehn, and Klaus Burger*
*Department of Organic Chemistry, University of Leipzig, Johannisallee 29, D-04103 Leipzig, Germany
Abstract
Hexafluoroacetone-protected glutamic acid on treatment with thionyl chloride is transformed into a carboxy-activated pyroglutamic acid derivative. Likewise, the reaction sequence can be applied to aminoadipic acid and homologues.
Published online: 4th August, 2003
■ Synthesis of Azulenequinones Fused with Thiophene and Furan
Hideyuki Matsuo, Kunihide Fujimori,* Akira Ohta, Akikazu Kakehi, Masafumi Yasunami, and the late Tetsuo Nozoe
*Department of Chemistry, Faculty of Science, Shinshu University, Matsumoto 390-8621, Japan
Abstract
1,5- And 1,7-azulenequinones fused with a thiophene or furan ring have been synthesized by bromine oxidation of azuleno[1,2-b]thiophenes, azuleno[2,1-b]thiophene, and azuleno[1,2-b]furan in aqueous THF.
Published online: 25th August, 2003
■ Reactions of Naphtho[b]cyclopropene with Isothiocyanate Derivatives to Give [2π + 2σ] Type Cycloadducts Using the Thiocarbonyl Moieties as 2π Components
Katsuhiro Saito,* Satoshi Hagari, Naoko Ito, Tomoko Kuriyama, Katsuhiko Ono, and Masakazu Ohkita
*Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Abstract
Thermal reactions of naphtho[b]cyclopropene with isothiocyanate derivatives afforded [2π + 2σ] type cycloadducts using the thiocarbonyl moieties as 2π components in moderate yields. The product yields were promoted by the use of a catalytic amount of Yb(fod)3. The structures of the products were determined by a single crystal X-Ray analysis.
Published online: 11th August, 2003
■ Synthetic Studies of Proanthocyanidins. Part 4. The Synthesis of Procyanidin B1 and B4: TMSOTf-catalyzed Cyclization of Catechin and Epicatechin Condensation
Akiko Saito, Noriyuki Nakajima,* Akira Tanaka, and Makoto Ubukata
*Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398
Abstract
Highly stereoselective synthesis of 3,4-trans series of (+)-catechin and (-)-epicatechin dimers under intramolecular condensation is described. Intramolecular condensation achieved an equimolar amount of coupling with 3,4-trans stereoselectivity and we succeeded in the synthesis of two 3,4-trans natural procyanidins, procyanidin-B1and B4.
Published online: 6th October, 2003
■ Asymmetric Synthesis of 1-Substituted 1,2,3,4-Tetrahydroisoquinolines by Asymmetric Electrophilic α-Amidoalkylation Reactions
Matthias Ludwig,* K. Polborn, and Klaus T. Wanner*
*Department Pharmazie, Zentrum für Pharmaforschung, LMU München, Butenandtstr. 5-13 D-81377 München, Germany
Abstract
An efficient method for the asymmetric synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via chiral N-acyliminium ions is presented. The N-acyl-1,2-dihydroisoquinolines (8) and (9) underwent smooth oxidation reactions with Ph3C+BF4- to give the chiral N-acylisoquinolinium ions (10) and (13), respectively. Stereoselective addition of organomagnesium and organozinc compounds to intermediates (10) and (13) provided the corresponding 1-substituted N-acyl-1,2-dihydroisoquinolines (11/12) and (14/15) in good yields. The diastereoselectivity of these reactions appeared to be dependent on the structure of the N-acyliminium ion intermediates (10) and (13) and on the nature of the trapping reagent with the zinc reagents in general leading to markedly improved stereoselectivities. Pure diastereomers were obtained by preparative HPLC and readily transformed into enantiopure 1-substituted 1,2,3,4-tetrahydroisoquinolines by catalytic hydrogenation and reductive removal of the chiral auxiliary.
Published online: 11th August, 2003
■ Synthesis of A-Ring Synthon of 2α-Substituted Vitamin D3 Analogues Utilizing Grignard Reaction towards Methyl 2,3-Anhydro-4,6-O-benzylidene-α-D-mannopyranoside
Shinobu Honzawa, Yasuhiro Yamamoto, Koshiro Hirasaka, Hiroaki Takayama, and Atsushi Kittaka*
*Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
Abstract
A concise route to the Trost A-ring precursor enyne for synthesizing 2α-substituted 1α,25-dihydroxyvitamin D3 (1) is described, in which the 2α-substituents could be introduced via addition reaction of Grignard reagent towards the sugar epoxide, easily obtained from D-glucose. In the reaction, the solvent effect was remarkable and the use of toluene gave higher chemical yield and chemical reactivity as compared with ethereal solvents.
Published online: 7th August, 2003
■ Synthesis of Azulenylheterocyclic Compounds Using 2-(2-Azulenyl)ethynyltriphenylphosphonium Bromide
Shunji Ito, Shiro Moriyama, Masashi Nakashima, Masataka Watanabe, Takahiro Kubo, Masafumi Yasunami, Kunihide Fujimori, and Noboru Morita*
*Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Abstract
2-(2-Azulenyl)ethynyltriphenylphosphonium bromide was prepared from 2-formylazulene. Its NMR spectroscopic property was made clear. Furthermore, its reactivity with o-substituted aniline was examined. We found that 2-(2-azulenyl)ethynyltriphenylphosphonium bromide reacted with o-substituted aniline to give corresponding 2-(2-azulenyl)benzoazoles.
Published online: 22nd September, 2003
■ Synthesis and the Extractability of Aminobenzocrown Ether Derivatives Connected by an Azulenequinone: Azulene-bis(aminobenzo-15-crown-5) Framework as a Useful Potassium Cation Capture
Ohki Sato,* Koichi Kaneko, Tsuyoshi Okano, and Josuke Tsunetsugu*
*Department of Chemistry, Faculty of Science, Saitama University, Saitama, Saitama 338-8570, Japan
Abstract
Bis(aminobenzocrown ether)s connecting with azulenequinones (6 – 9) were prepared by the nucleophilic substitution reaction of the corresponding dibromo-azulenequinones (5) with 4’-aminobenzo-15-crown-5 or -18-crown-6 and the high extractability of 3,7(5)-bis(aminobenzo-15-crown-5)-azulenequinones (8) for potassium cation was revealed and explained by a plausible 2/1 sandwich-type complex formation.
Published online: 16th September, 2003
■ Effect of Pyridine on Polymorphic Crystallization of 1,3-Di(9-anthryl)propan-2-ol. Does It Affect π/π Interaction or Hydrogen Bonding?
Naoto Hayashi,* Takashi Mori, Kumiko Yamaguchi, Naoki Tsukamoto, and Kiyoshi Matsumoto*
*Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan
Abstract
Effect of pyridine on polymorphic crystallization of 1,3-di(9-anthryl)propan-2-ol (1) is investigated by X-Ray analyses. 1 generally crystallizes in α-form, whereas the 1:1 solvate (γ-form) was obtained from pyridine solution, in which pyridine was shown to serve largely as a hydrogen-bond acceptor preventing hydrogen bonding between molecules of 1 in crystallization process.
Published online: 2nd October, 2003
■ Synthesis and Reaction of Bromoallylsilane: A Short Access to β,γ-Disubstituted α-Methylene-γ-butyrolactone
Jun’ichi Uenishi* and Masashi Ohmi
*Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
Abstract
(Z)-β-Bromoallylsilanes (1a-c) were prepared by a stereoselective Ni-catalyzed cross-coupling reaction of 1,1-dibromo-4-phenylbutene (4) with silylmethylmagnesium halide. Sakurai-Hosomi reaction of 1a with aldehyde gave syn-3-alkyl-2-bromo-4-hydroxyalkene (2a, 2c, and 2e) and that with acetal gave syn-4-alkoxy-3-alkyl-2-bromoalkene (2b and 2d) stereoselectively. The products with formyl function reacted with a Ni-carbonyl complex to give β,γ-disubstituted α-methylene-γ-butyrolactones (3) in good yields. Pd-catalyzed cross-coupling reaction of 1a-c or 4 with silylmethylmagnesium halide gave 1,1-bis(silylmethyl)-1-alkenes (1d-i), which reacted with dimethyl acetal to generate more functionalized allylsilane (6).
Published online: 9th October, 2003
■ Facil Synthesis of 4a-Fluoro-5,10-ethenobenzo[f]quinazolines through 1,4-Photocycloaddition of 5-Fluoro-1,3-dimethyluracil with Substituted Naphthalenes
Kazue Ohkura, Tatsuyuki Sugaoi, Tetsuya Ishihara, Kazuya Aizawa, Ken-ichi Nishijima, Yuji Kuge, and Koh-ichi Seki*
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
UV-irradiation of 6-chloro-1,3-dimethyluracil with naphthalenes underwent 1,2-cycloaddition to give naphthocyclobutapyrimidines consisting of a cyclobutene ring, The same reaction of an aprotic solution of 5-fluoro-1,3-dimethyluracil and naphthalenes bearing various substituents underwent 1,4-cycloaddition mode-selectively to give the corresponding ethenobenzoquinazoline derivatives with H and F atoms remaining intact on the newly constructed barrelene moiety. In protic solvents, the reaction preferentially proceeded by way of a substitution reaction to afford 5-(1-naphthyl)uracil.
Published online: 6th October, 2003
■ Synthesis and Evaluation of Novel Dirhodium(II) Carboxylate Catalysts with Atropisomeric Biaryl Backbone
Ken Hikichi, Shinji Kitagaki, Masahiro Anada, Seiichi Nakamura, Makoto Nakajima, Motoo Shiro, and Shunichi Hashimoto*
*Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Hokkaido
Abstract
Three new dirhodium(II) carboxylate catalysts containing an axially dissymmetric biphenyl or binaphthyl skeleton have been synthesized and characterized. The X-Ray structure of the dirhodium(II) complex incorporating (R)-2'-methoxycarbonyl-6,6'-dimethyl-[1,1'-biphenyl]-2-carboxylate as bridging ligands demonstrates that the four carboxylate ligands are arranged in a C2-symmetry-like conformation. These catalysts have been shown to provide a reasonable level of asymmetric induction in intramolecular C—H insertion of α-methoxycarbonyl-α-diazoacetamide.
Published online: 20th October, 2003
■ Synthesis and Conformational Studies of 3’-(2’-Aminoborane-2’-deoxyuridyl)-5’-thymidilyl Hydrogen Phosphate to be Used in the Construction of Oligonucleotide Sequences
Luigi Piero Stasi, Claudia Mugnaini, Stefano Alcaro, Federico Corelli,* and Maurizio Botta*
*Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via A. Moro, snc 53100 Siena, Italy
Abstract
The synthesis of the boronated dinucleotide (2) starting from commercially available building blocks was accomplished according to the phosphoramidite approach. The dimer, which can be used in the construction of oligonucleotide sequences, is itself interesting for its potential applications in Boron Neutron Capture Therapy and as a possible inhibitor of HIV-1 integrase. Computational studies were also performed showing its preferential C3’-endo (RNA-like) conformation.
Published online: 14th October, 2003
■ Syntheses and Spectroscopic Properties of Methylbenzoate Derivatives of Tetrabenzoporphyrin, Application to Circular Dichroism Studies
Maryline Giraud-Roux, Gloria Proni, Koji Nakanishi,* and Nina Berova*
*Department of Chemistry, Columbia University, New York, New York 10027, U.S.A.
Abstract
The syntheses, UV-VIS and fluorescence data of two methylbenzoate derivatives of tetrabenzoporphyrins, i.e., 5-p-methoxycarbonylphenyl-tetrabenzoporphyrin (TBPPhCO2Me), 5-p-methoxycarbonylphenyl-10,15,20-triphenyltetrabenzoporphyrin (TPTBPCO2Me), and their zinc and magnesium complexes are described. The latter was tested as a bis(zinc-porphyrin) host in the CD-based molecular recognition studies because of its expanded surface compared to the conventional porphyrin rings and its red shifted Soret band with a large extinction coefficient.
Published online: 2nd October, 2003
■ A New Synthesis of Functional Dyes from 2-Acenaphtho[1,2-c]pyrrole
Noboru Ono,* Takanori Yamamoto, Naomi Shimada, Kenji Kuroki, Mitsuo Wada, Ryouhei Utsunomiya, Tomoko Yano, Hidemitsu Uno, and Takashi Murashima
*Departmnt of Chemistry, Faculty of Science, Ehime University, Matsuyama 790-8577, Japan
Abstract
Incorporation of acenaphtho[1,2-c]pyrrole units into the π-conjugated systems is very effective to get the narrow HOMO-LUMO gap materials, and the absorption spectra of π-conjugated polymers, porphyrins, and boron dipyrromethene dyes fused with acenaphthene rings are extensively red-shifted.
Published online: 27th October, 2003
■ A New Convenient Method for Synthesis of 3-(2-Oxoethylidene)isoindolin-1-ones Employing Palladium(II) Acetate and DDQ
Akiharu Ueki, Satoru Tanaka, Masunori Kumazawa, Takashi Ooi, Shigeki Sano, and Yoshimitsu Nagao*
*Faculty of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Abstract
Treatment of 2-alkyl-3-hydroxy-3-vinylisoindolin-1-ones with 10 mol % of Pd(OAc)2 and 1 mol eq. of DDQ in THF under reflux gave 3-(2-oxoethylidene)isoindolin-1-ones in 65-80% yields.
Published online: 4th November, 2003
■ Stereospecific Access to β-Mannosides from Glucose-derived 1,2-Orthoesters as Glycosyl Donors
Eisuke Kaji,* Yugo Hosokawa, Yusuke Watanabe, Mina Kobayashi, and Mayumi Yamakawa
*School of Pharmaceutical Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan
Abstract
A new, stereospecific synthesis of β-mannosides from glucose-derived 1,2-orthoesters has been developed by a simple four step procedure, comprising β-specific glycosidation of the 1,2-orthoesters, 2’-O-deacetylation, 2’-O-triflation, and SN 2 type inversion of the triflyl group providing β-D-Man-(1→6)-D-Gal, and β-D-Man-(1→4)-D-Glc derivatives in reasonable yield.
Published online: 20th October, 2003
■ New Chiral Phosphinooxathiolane Ligands for Palladium-catalyzed Asymmetric Allylations
Hiroto Nakano,* Yuko Okuyama, Ryo-suke Takahashi, and Reiko Fujita
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
A new chiral phosphinooxathiolane ligands were synthesized and their abilities as chiral catalysts were examined in palladium-catalyzed allylic alkylation and amination.
Published online: 20th October, 2003
■ Synthesis of Both Enantiomers of Brevioxime and Determination of Its Absolute Configuration
Yutaka Nishimura, Ken Ishigami, and Takeshi Kitahara*
*Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Abstract
Brevioxime is an inhibitor of juvenile hormone biosynthesis, isolated from Penicillium brevicompactum. We synthesized both enantiomers of brevioxime and determined the absolute configuration of natural product as S.
Published online: 20th October, 2003
■ [4+2] Cycloaddition Reactions of Neutral 2-Azadienes with Electron-deficient Dienophiles
Francisco Palacios,* Concepción Alonso, Gloria Rubiales, Cristina Tobillas, and José María Ezpeleta
*Departamento de Química Orgánica, Facultad de Farmacia, Universidad del País Vasco, Apartado 450, 01080 Vitoria, Spain
Abstract
A method for the preparation of functionalized tetrahydropyridine and triazine derivatives is described, based on aza Diels-Alder reaction of neutral 2-aza-1,3-dienes with electron-poor dienophiles as tetracyanoethylene and N-phenyl-1,2,4-triazoline-3,5-dione.
Published online: 19th May, 2003
■ Copper-catalyzed N-Arylation of 2-Oxazolidinones. An Expeditious Route to Toloxatone
Sandro Cacchi,* Giancarlo Fabrizi, and Antonella Goggiamani
*Department of Chemistry and Technology of Biologically Active Substances, University of Rome “La Sapienza”, P.le A. Moro 5, 00185 Rome
Abstract
3-Aryl-2-oxazolidinones are obtained in excellent yields through the copper-catalyzed N-arylation of 2-oxazolidinones with a variety of aryl iodides. With aryl halides containing both iodo and bromo substituents, a high C-I/C-Br selectivity can be achieved. The procedure has been successfully applied to the preparation of a key intermediate in the synthesis of linezolid and to develop an expeditious route to toloxatone.
Published online: 13th May, 2003
■ Synthetic Studies on Pyrrolophenanthridone Skeleton from 1-Benzoyl-7-iododihydroindole Derivatives Using Palladium-assisted Biaryl Coupling Reactions
Takashi Harayama,* Hiroko Toko, Akihiro Hori, Taeko Miyagoe, Tomonori Sato, Hiromi Nishioka, Hitoshi Abe, and Yasuo Takeuchi
*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
The biaryl coupling reaction of 1-benzoyl-7-iododihydroindole derivatives using Pd reagent was examined. 1-[(1,3-Benzodioxol-5-yl)carbonyl]-7-iodo-2,3-dihydroindole gave 4,5-dihydro-7H-[1,3]dioxolo[4,5-k]pyrrolo[3,2,1-de]phenanthridin-7-one, which was formed by connection to a more hindered carbon, as a major product. 1-(3,4-Dimethoxybenzoyl)-7-iodo-2,3-dihydroindole gave oxoassoanine and 10,11-dimethoxy-4,5-dihydropyrrolo[3,2,1-de]phenanthridin-7-one in an almost equal ratio.
Published online: 10th June, 2003
■ An Attempt for Biaryl Coupling Reaction of Benzyl Benzoate Derivatives under Ullmann Conditions
Hitoshi Abe,* Shigemitsu Takeda, Yasuo Takeuchi, and Takashi Harayama*
*Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan
Abstract
The biaryl coupling reaction of benzyl benzoate derivatives (3) and (4) was examined with copper(0) reagent. A dimerized product (9) was mainly obtained whereas the desired intramolecularly coupled product (11) was not detected when 3 was employed as the substrate. On the other hand, the reaction of 4 afforded a small amount of the desired lactone (14) although the main product was the dimerized 12.
Published online: 4th July, 2003
■ Racemic N1-Norphenserine and Its Enantiomers: Unpredicted Inhibition of Human Acetyl- and Butyrylcholinesterase and β-Amyloid Precursor Protein in vitro
Qian-sheng Yu, Weiming Luo, Harold W. Holloway, Tada Utsuki, Tracy Ann Perry, Debomoy K. Lahiri, Nigel H. Greig,* and Arnold Brossi
*Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825, U.S.A.
Abstract
The optically pure enantiomers of N1-norphenserine (15, 16) were synthesized and its racemate 17 was prepared by mixing equal parts of each enantiomer. (-)-N1-Norphenserine (15) was prepared by partial synthesis initiated from the natural product, (-)-physostigmine (1). (+)-N1-Norphenserine (16) was prepared by total synthesis using the Julian oxindole route, with modifications. The in vitro inhibitory activities of 15-17 were quantified against human erythrocyte AChE and plasma BChE as well as against human neuroblastoma cell β-amyloid precursor protein secretion in cell culture. All were active. Racemic compound (17) with a high AChE and β—amyloid precursor protein inhibitory action may warrant further assessment in Alzheimer’s disease models.