HETEROCYCLES

■ Academic Studies by Professor Tetsuji Kametani

Keiichiro Fukumoto*

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

■ Papers of Professor Tetsuji Kametani

Tetsuji Kametani*

*Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

■ Synthesis of Stable 7-Phosphanorbornadiene P-Oxides

Kiyoshi Matsumoto,* Shiro Hashimoto, and Takane Uchida

*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Nonbenzo-annelated stable 7-phosphanorbornadiene P-oxides have been prepared for the first time by the high pressure Diels-Alder reaction of 1,2,3,4,5-pentaphenylphosphole oxide with diaroylacetylenes. The P-oxides decompose around 100°C to give the 1,2-diaroyl-3,4,5,6-tetraphenylbenzenes.

■ A New Bisbenzylisoquinoline Alkaloid from Phaenthus vietnamensis and Its Antibacterial Activity

Petr Sedmera, Nguyen Thi Nghia, Ivo Válka, André Cavé, Diego Cortés, and Vilím Simánek*

*Institute of Medical Chemistry, Palacky University, 3, Hnevotínská, 775 15 Olomouc, Czech Republic

Abstract

A new bisbenzylisoquinoline alkaloid (-)-(1S,1’R)-O,O’-dimethylgrisabine (1) was isolated the leaves of Phaeanthus vietnamensis Ban. Its structure was determined on the basis of the extensive 2-D and 1-D nmr long-range heteronuclear correlations. Its antibacterial activity is also described.

■ Synthesis of Nucleosides and Their Related Compounds. 15. Dimethyl rel-(1S,2S,3R,4R)-2-(2,3-Epoxy-4-hydroxymethylcyclopent-1-yl)Malonate as a Novel Building Block for Carbocyclic Arabinosyl Nucleosides

Nobuya Katagiri, Masahiro Nomura, and Chikara Kaneko

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Dimethyl 3-acetoxy-5,6-exo-epoxybicyclo[2.2.1]heptane-2,2-dicarboxylate (1) has been synthesized by epoxidation of the Diels-Alder adduct of dimethyl acetoxymethylenemalonate with cyclopentadiene and on reductive retrograde aldol reaction afforded dimethl rel-(1S,2S,3R,4R)-2-(2,3-epoxy-4-hydroxymethylcyclopent-1-yl)malonate (2), which serves as the direct precursor of carbocyclic arabinosyl nucleosides. Synthesis of the related bicyclo-epoxides and their reactions are also described.

■ Synthesis of 1,3-Dioxin-4-ones and Their Use in Synthesis. 21. Intramolecular Photo[2+2]cycloaddition Reactions of Chiral Spirocyclic Dioxinones Having ω-Alkenyl Groups at 3-Position

Masayuki Sato,* Yoshito Abe, Chikara Kaneko,* Toshio Furuya, and Noriyoshi Inukai

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Chiral spirocyclic dioxinones having an ω-alkenyl group at 3-position were synthesized and their intramolecular photo[2+2]cycloaddition reactions were examined. The results not only provide enantioselective synthetic route to 2S-acetonylcyclohexanecarboxylic acids but also clarify the reason why these dioxinones exhibit remarkable diastereofacial selectivities in both intra- and intermolecular photo[2+2]cycloaddtion reactions.

■ 4,5,6,7-Tetrahydroisobenzofuran-5-one as a Versatile Building Block Leading to the Basic Skeleton of Naturally Occurring Fused Furans

Yasuchika Yamaguchi, Noriaki Tatsuta, Seizo Soejima, Kenji Hayakawa, and Ken Kanematsu*

*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

Abstract

4,5,6,7-Tetrahydroisobenzofuran-5-one as a building block has been prepared via the furan ring transfer (FRT) reactions utilizing an allene intramolecular Diels-Alder reaction, which provides a single route to the construction of the tricyclic furans.

■ Pyrano[3,2-c]azepine, a New Heterocyclic System. A New Approach to Pyrido[3,2-c]azepines

Marijan Kocevar,* Slovenko Polanc, Miha Tisler, and Bojan Vercek

*Department of Chemistry and Chemical Technology, E. Kardelj University, Murnikova 6, 61000 Ljubljana, Slovenia

Abstract

3-Benzoylamino-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydrocoumarin (1a) was used as a synthon in the preparation of the first derivatives of the pyrano[3,2-c]azepine system 2 and in two approaches to pyrido[3,2-c]azepines 4.

■ Syntheses of Pyrido[2,3-d]pyrimidine Nucleosides via 6-Allylaminouridines from 6,5’-Anhydroridine Derivative and Allyamines

Tsuneo Itoh,* Ichiro Ishikawa, Yasuo Tomii, Yoshihisa Mizuno, Haruo Ogura, and Norio Kawahara

*School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan

Abstract

Pyrido[2,3-d]pyrimidine nucleosides were readily synthesized by treatment of 2’,3’-O-isopropylidene-6-allylaminouridines, which were derived from 6,5’-anhydro-2’,3’-O-isopropylidene-6-hydroxyuridine and allylamines with palladium(II) acetate.

■ Synthesis of Novel Carbo- and Heteropolycycles. 17. Intramolecular 1,3-Dipolar Cycloaddition Reaction of 3-endo-Azidobicyclo[3.3.1]non-6-ene. A Facile Route to 5-Azaprotoadamant-4-ene

Shoji Eguchi,* Takanori Suzuki, Nao Toi, and Tadashi Sasaki

*Faculty of Engineering, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan

Abstract

The intramolecular 1,3-dipolar cycloaddition of 3-endo-azidobicyclo[3.3.1]non-6-ene 1 proceeded on heating in toluene under reflux to afford regioselectively very unstable 1,2,3-triazoline derivative 2, which decomposed spontaneously in MeOH to give exclusively 5-azaprotoadamant-4-ene 6.

■ Investigation of Stereochemical Control for Steroid Side Chain by Kinetic Protonation of Tetronate Derivatives

Toshio Honda,* Hironao Takada, Tadashi Katoh, and Masayoshi Tsubuki

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Stereochemical control for construction of steroidal side chains by kinetic protonation of tetronate derivatives is described. Kinetic protonation of the (22R)-tetronates (4 and 11) proceeded with the inversion of the stereochemistry at the C-22 position to afford the corresponding (22S)-tetronates (3 and 12), whereas the same treatment of 9a and 9b gave only a mixture of stereoisomers. Furthermore, isomerization of the double bond of 7a and 7b led to the formation of (20E)-olefin (8a) and (20Z)-olefin (8b) (84:16) with moderate stereoselectivity.

■ Synthesis of Amphikuemin and Analogs: A Synomone That Mediates Partner-Recognition between Anemonefish and Sea Anemone

Katsuhiro Konno,* Guo-wei Qin, Koji Nakanishi, Michio Murata, and Yoko Naya

*The Institute of Food Chemistry, 1-1-1, Wakayamadai, Shimamotocho, Mishimagun, Osaka 618-0024, Japan

Abstract

Amphikuemin (1), a compound that is responsible for partner-recognition at the first encounter between anemonefish and sea anemones, has been synthesized to confirm its structure and to supply material for further biological studies. Synthesis of amphikuemin analogs (11-15) is also described.

■ Alkoxide-mediated Oxidative Ring Expansion of Benzocyclobutenes. A New Route to 3,4-Dihydroisocoumarines

Kozo Shishido, Kou Hiroya, Akitake Yamashita, Yuji Tokunaga, and Keiichiro Fukumoto*

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Sequential treatment of the dianion of 6 with a variety of esters (10) and MoO₅·pyridine·HMPA complex provided the rearranged 2-hydroxy-1-indanones (7) along with the 1-acylbenzocyclobutenes (8), which were easily converted to 7. Transformation of 7 to the 3,4-dihydroisocoumarines (9) was achieved by oxidative cleavage followed by reduction and acid treatment.

■ Synthesis of an Optically Active Tricyclic Intermediate for Manzamines

Karel M. J. Brands and Upendra K. Pandit*

*Organic Chemistry Department, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands

Abstract

L-Serine has been converted into a chiral pyrrolo[2,3-i]isoquinoline derivative which can serve as a potential intermediate for manzamines.

■ Diastereoselective Synthesis of 2,6-Disubstituted 3-Hydroxypiperidine, 2-(α-Hydroxyalkyl)-3-hydroxypiperidine and 2-(α-Hydroxyalkyl)-3-hydroxypyrrolidine Derivatives

Shinzo Kano,* Yoko Yuasa, Naoki Mochizuki, and Shiroshi Shibuya

*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

Reduction of 5-substituted 5,8a-trans-oxazolo[3,4-a]pyridin-8-ones (7a,b), obtained by an application of α-acylamino radical cyclization at the initial stage, with NaBH₄ and K-Selectride was found to proceed with complete stereocontrol in all cases. Reduction of 1-substituted 1,8a-trans-oxazolo[3,4-a]pyridin-8-one (7c) and pyrrolidine analogue (10) with NaBH₄ and K-Selectride was also found to proceed with high diastereoselectivity.

■ R-(+)- and S-(—)-Tetrahydroharmine: Preparation of Optically Pure Alkaloids and Acid-Catalyzed Racemization

Linda A. Chrisey and Arnold Brossi*

*Section of Medicinal Chemistry, Laboratory of Bioorganic Chrmistry, NIDDK, National Institute of Health, Bethesda, MD 20892, U.S.A.

Abstract

Chemical resolution of (+)-tetrahydroharmine (2) with optically active 10-camphorsulfonic acids afforded 1R-(+)-tetrahydroharmine (3A) as well as the 1S-(-)-isomer, 3B. Hplc analysis of ureas obtained by reaction with 1R-(+)-(1-phenylethyl)isocyanate demonstrated that the bases were greater than 98% optically pure. Racemization of 3A occurred in acidic solutions.

■ The Firat Synthesis of Mutagenic Trp-P-1 via the Electrocyclic Reaction of 1-Azahexa-1,3,5-triene System

Satoshi Hibino,* Eiichi Sugino, Naoki Sgura, Yohko Shintani, and Kohichi Sato

*Graduate School of Pharmacy and Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan

Abstract

The first total synthesis of Trp-P-1 (1) has been completed by the thermal electrocyclic reaction of 1-azahexa-1,3,5-triene system (3).

■ Mechanism of BF₃·Etherate-Catalyzed Rearrangement of Fucosterol Epoxide

Yoshinori Fujimoto,* Yoji Ikuina, Yoko Kanzawa, Mitsuhiro Nagakari, Katsumi Kakinuma,* and Nobuo Ikekawa

*Department of Chemistry, Faculty of Science, Tokyo Instituteof Technology, Meguro-ku, Tokyo 152-8552, Japan

Abstract

The mechanism of the BF₃·etherate-catalyzed rearrangement of fucosterol benzoate 24,28-epoxide (1) leading to desmosterol benzoate (2) and two carbonyl compounds (3) and (4) was investigated.

■ Photochemical Oxygenation of Olefins by Heterocyclic N-Oxides: Mechanistic Characteristics in the Photochemistry of Pyrimido[5,4-g]-pteridine-10-oxide

Yoshifumi Maki,* Mogoichi Sako, Toshinobu Murase, Yukio Kitade, and Kosaku Hirota

*Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan

Abstract

A nobel heterocyclic N-oxide, pyrimido[5,4-g]pteridine-10-oxide (1), oxygenates cyclohexene (4) and norbornene (9) under the photochemical conditions to give the corresponding oxidation products, (5)-(8) and (10)-(12), respectively. Experimental results clearly indicate that the photochemical oxygenation by (1) involves a single-electron transfer from the olefins (4) and (9) to the single-excited (1) followed by oxygen-atom transfer rather than oxene mechanism.

■ Intra- and Intremolecular Palladium-Catalyzed Asymmetric Allylations of Chiral Enamines

Kunio Hiroi* and Jun Abe

*Department of Synthetic Organic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

Stereochemistry of intramolecular palladium-catalyzed asymmetric allylations of chiral enamines involving allylating species in the molecules is discussed, compared with that of intermolecular reactions. The mechanistic pathway for this asymmetric induction is proposed on the basis of the stereochemical results.

■ Asymmetirc Induction by Chiral Heterocyclic Compounds: Highly Diastereoselective Reaction of 5-Oxa-7,8a-diazaperhydroazulen-8-ones with Organometallic Reagents

Hiroshi Takahashi,* Ichiro Morimoto, and Kimio Higashiyama

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

1) New chiral heterocyclic compounds, 5-oxa-7,8a-diazaperhydroazulen-8-ones (3a-c), were synthesized from (S)-prolinol (1) and potassium cyanate, followed by the condensation with aldehydes. 2) Extremely high diastereoselective reaction of the 3a-c with diethylzinc proceeded with a facil procedure to give (2S, 1’S)-N-1’-arylpropyl-2-hydroxymethyl-1-pyrrolidinecarboxamide (4a-c). 3) The reduction of 4a-c with Red-Al gave (S)-1-aryl-N-methylpropylamines (5a-c) and (S)-prolinol (1) in good yields.

■ Constutuions of Forsythosides F and G, New Phenol Glycosides of Forsythia viridissima Stems

Katsuya Endo* and Kazuhiro Takahashi

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Two new phenol glycosides forsythoside F (1) and forsythoside G (2) have been isolated from Forsythia viridissima stems and their structures were established based on the spectroscopic data and chemical transformations. D-2-O-methylapiose was for the first time characterized in the natural product.

■ Novel Reaction of a Stable Selenanaphthalene, 1-Cyano-2-methyl-2-selenanaphthalene with Electrophiles

Mikio Hori,* Tadashi Kataoka, Hiroshi Shimizu, Kazuhiro Tsustsumi, and Mitsuhiro Yoshimatsu

*Department of Pharmacognosy, Gifu College of Pharmacy, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan

Abstract

Reactions of 1-cyano-2-methyl-2-selenanapgtharene (I) with dimethyl acetylenedicarboxylate gave benzocycloheptene derivatives, II and IV, and naphthalenedicarboxylate III, while olefinic electrophiles such as acrylonitrile, methyl acrylate, and methyl vinyl ketone reacted with I to afford the cyclopropane derivatives, XII and XIII.

■ A Novel Synthesis of Cyclohexylnorstatine Isopropyl Ester, the C-Terminal Component of a Renin Inhibitor

Yoshio Ito, Tetsuhide Kamijo, Hiromu Harada, and Shiro Terashima*

*Sagami Central Research Center, Hayakawa, Ayase, Kanagawa 252-1193, Japan

Abstract

The title compounds was produced diastereoselectively in recemic and optically active forms by employing the [2+2] cycloaddition reaction of an imine with benzyloxyketene followed by acidic alcoholysis of the formed 3,4-cis-disubstituted β-lactam with isopropanol.

■ A Convenient Synthesis od Substituted Heteroaromatic Compounds via the Palladium-Catalyzed Cross-Coupling Reaction of Organosilicon Compounds

Yasuo Hatanaka, Satoshi Fukushima, and Tamejiro Hiyama*

*Sagami Central Research Center, Hayakawa, Ayase, Kanagawa 252-1193, Japan

Abstract

The silicon-based cross-coupling reaction promoted by fluoride ion and a Pd Catalyst provides us with a new entry to substituted heteroaromatic compounds.

■ Enantioselective Deprotonation of the Meso-Forms of 2,6- and 3,5-Dimethylcyclohexanones

Hee-doo Kim, Ryuichi Shirai, Hisashi Kawasaki, Makoto Nakajima, and Kenji Koga*

*Faculty of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

Kinetic deprotonation of meso-dimethylcyclohexanones (1a-c) by chiral lithium amides (2a-c) in the presence of excess trimethylsilyl chloride afforded the corresponding silyl enol ethers (3a-b) in good yields and in reasonably high enantiomeric excesses.

■ Comformational Difference between Erythrinan- and Homoerythrinan-3-ones: Total Synthesis of (±)-Schelhammeridine and (±)-3-Epischelhammeridine

Yoshisuke Tsuda,* Shinzo Hosoi, and Masami Murata

*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan

Abstract

Erythrinan- and homoerythrinan-3-ones behave differently toward hydride reductions suggesting their conformational difference: for example, Δ¹-erythrinan-3-one gives 3α-alcohol and Δ¹-domoerythrinan-3-one gives 3β-alcohol stereoselectively on reduction with NaBH₄-CeCl₃ in methanol. Based on these observations, total syntheses of homoerythrinan alkaloids, schelhammeridine and 3-epischelhammeridine, and an erythrinan alkaloid, 8-oxoerysotrine, were accomplished.

■ Electrophilic Substitution in Indoles, Part 18. Hammett Correlations of the Coupling of Aryl Diazonium Tetrafluoroborates with Indoles

Meysun I. Adbullah, Anthony H. Jackson,* Patrick P. Lynch, and Keith A. F. Record

*School of Chemistry and Applied Chemistry, College of Cardiff, University of Wales, Cardiff CF1 3TB, Wales, U.K.

Abstract

Hammett plots for the coupling of a series of substituted aryldiazonium salts with indole and 3-methylindole show linear relationships thus confirming that the reactions are typical aromatic electrophilic substitutions.

■ Stereocontrolled Synthesis of C₁₈-C₂₄ Fragments of Isolasalocid A and Lasalocid A. An application of the Acid Assisted Synthesis of Functionalized Tetrahydrofurans and Tetrahydropyrans

Kiyoshi Horita, Ichio Noda, Kazuhiro Tanaka, Tamaki Miura, and Osamu Yonemitsu*

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

The allyl alcohol (9) derived from D-glucose was easily cyclized by acid treatment and then converted to the C₁₈-C₂₄ fragment (13) of isolasalocid A (5). Similarly, the allyl alcohol (15) derived from ethyl L-lactane was converted to the C₁₈-C₂₄ fragment (20) of lasalocid A (6) via the tetrahydropyran derivative (16), which was kinetically formed by a chelation-controlled reaction.

■ Biomimetic Synthesis of Koumine by the Palladium-Catalyzed Intramolecular Coupling Reaction of 18-Hydroxytaberpsychine (18-Hydroxyanhydrovobasinediol)

Hiromitus Takayama, Mariko Kitajima, and Shin-ichiro Sakai*

*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

A principal Gelsemium alkaloid, koumine (1) was synthesized from 18-hydroxygardnutine (3) via the demethoxylation from the indole ring and the palladium-catalysed cyclization between C₇ and C₂₀ of the hypothetical biogenetic intermediate, 18-hydroxytaberpsychine (2).