HETEROCYCLES

■ Biographical Data

Yoshio Ban*

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

■ Publications

Yoshio Ban*

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

■ Yoshio Ban (1921-1994) , Ambassador for Japanese Chemistry

William G. Dauben and Masato Tanabe

*Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, U.S.A.

■ Professor Yoshio Ban (1921-1994)

Yuichi Kanaoka and Tohru Hino

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

■ Sysnthesis and DNA Photo-cleaving Activity of Novel Heterocyciclic N-oxide - Acridine Hybrid Molecules

Magoichi Sako, Yoshifumi Takeda, Kosaku Hirota, and Yoshifumi Maki

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

Abstract

The novel DNA photo-cleaver consisting of the heterocyclic N-oxide, which is an efficient photochemical generator of hydroxyl radicals, an acridine intercalator, and an amide-type methylene linker was designed and synthesized. The preliminary DNA strand-breakage study of the hybrid compounds demonsfrated that the DNA photo-cleaving activity of the parent heterocyclic N-oxide increased by linking with the acridine intercalator.

■ Beckmann Rearrangement of 4,5,6-Trisubstituted 3-Acetylpyridin-2-one Oximes

Yutaka Yamamoto and Yoshitaka Ogawa

*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

Beckmann rearrangement of 4,5,6-trisubstituted 3-acetylpyridin-2-one oximes took place, involving equilibrium between the methyl-syn and -anti forms, to give exclusively 4,5,6-trisubstituted 3-acetylaminopyridin-2-ones in satisfactory yields.

■ An Asymmetric Synthesis of the Ant Venom Alkaloid (3S,5S,8aR)-3-Butyl-5-(4-pentenyl)indolizidine via the Sharpless Asymmetric Dihydroxylation

Hiroki Takahata, Hiroshi Bandoh, and Takefumi Momose

*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan

Abstract

The first asymmetric synthesis of the ant venom alkaloid (3S,5S,8aR)-3-butyl-5-(4-pentenyl)indolizidine (1) has been performed by starting with the Sharpless asymmetric dihydroxylation of N-alkenylcarbamate (3) followed by reductive annulation (5-exotetrahedral).

■ Theoretical Calculation-based Reproduction of Thermodynamic, Kinetic Behaviors and Cytotoxicity Azasteganes

Kiyoshi Tomioka, Motomu Kanai, and Nobuo Ikota

*The Institute of Scientific and Industrial Research, Osaka University, 8-1. Mihogaoka, Ibaraki, Osaka 567-0047, Japan

Abstract

Theoretical calculation of azasteganes indicates that the thermodynamic control is operative in the isomerization of the pivotal biphenyl bond of 1 and 2 and kinetic control in epimerization at the sp³ center of 3 and 4. The calculated structures qualitatively reproduce the structure-cytotoxicity relationships of azasteganes.

■ Preparation of Novel Cyclic Hypervalent Idoine(III) Compounds Having Azido, Cyano, and Nitrato Ligands

Shuji Akai, Takayuki Okuno, Masahiro Egi, Takeshi Takada, Hirofumi Tohma, and Yasuyuki Kita

*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan

Abstract

The title cyclic hypervalent iodine compounds (4-8) were prepared in good yields by the ligand exchange reaction of the acetoxy cyclic iodinanes (1-3) with trimethylsilyl compounds and of the chloro cyclic iodinane (9) with silver nitrate, and were found to be air-stable at room temperature.

■ Synthesis of Polycyclic Nitrogen-containing Heterocycles: One Pot Formation of 1,6-Naphthyridine Ring System by Reaction of Amino-cycano-methylyhio-heterocycles with Dialkyl Acetylenedicarboxylates

Yoshinori Tominaga and Noriko Yoshioka

*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

The reaction of 5-amino-6-cyano-1,3-dimethyl-7-methylthiopyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (1c) with dimethyl acetylenedicarboxylate (DMAD) in the presence of potassium carbonate in dimethyl sulfoxide gave tetramethyl 8,9,10,11-tetrahydro-8,10-dimethyl-9,10-dioxo-4H-pyrimido[4’,5’:5,6]pyrido[2,3,4-cb] [1,6]naphthyridine-2,3,5,6-tetracarboxylate (2c). The reaction of other heterocycles bearing amino, cyano, and methylthio groups with DMAD or DEAD under the same reaction conditions gave the corresponding tetracyclic heterocycles containing the fundamental 1,6-naphthyridine ring system.

■ Synthesis of N⁶,2’,3’,5’-Tetrabenzoyl-β-D-adenosine Catalyzed by Metal Iodides

Masashi Nagai, Takafumi Matsutani, and Teruaki Mukaiyama

*Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan

Abstract

N-Glycosylation of N⁶-benzoyl-N⁶,N⁶-bis(trimethylsilyl)adenine with methyl 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl carbonate was effectively promoted by several metal iodides and a desired coupling product, N⁶, 2’, 3’,5’-tetrabenzoyl-β-D-adenosine (3), was obtained in high yield when SbI₃ or TeI₄ was used as a catalyst. In the case of using SnI₂ as a catalyst, nearly equal amounts of 3 and 2’,3’,5‘-tribenzoyl-β-D-adenosine (4), a N⁶-debenzoylated product of 3, were produced in acetonitrile whereas 3 was obtained as a major product in other nitrile solvents.

■ An Enantioconvergent Construction of the Key Intermediate of (+)-Vincamine

Takahiro Yamane, Michiyo Ishizaki, Mahito Suzuki, Michiyasu Takahashi, Kou Hiroya, Seiichi Takano, and Kunio Ogasawara

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

Abstract

A key intermediate for the synthesis of (+)-vincamine, the major alkaloid of Vinca minor and an important cerebral vasodilatory agent, has been synthesized in an enantioconvergent way from either (R)- or (S)-enantiomer of 2-carbethoxy-2-cyclopenten-1-ol obtained by lipase-mediated resolution.

■ Highly Diastereoselective Oxidation of 1-Alkylsulfinyl-9-(alkylthio)dibenzothiophene with MCPBA in the Presence of Trifluoroboran Etherate

Takeshi Kimura, Hidetaka Nakayama, and Naomichi Furukawa

*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan

Abstract

1-Alkylsulfinyl-9-(alkylthio)dibenzothiophene was oxidized readily by mCPBA/Et₂O·BF₃ in CH₂Cl₂ at -78°C to give one diastereomeric isomer of 1,9-bis(alkylsulfinyl)dibenzothiophene in high yield.

■ Reaction of Lithium Trimethlsilydiazomethane with N,N-Dialkylamides of α-Keto Acids and N,N-Disubstituted α-Amino Ketones

Hideki Ogawa, Toyohiko Aoyama, and Takayuki Shioiri

*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

Abstract

Lithium trimethylsilyldiazomerhane smoothly reacted with N ,N -dialkylamides of α-keto acids and N ,N -disubstituted α-amino ketones to give 2-oxo-3-pyrrolines and 3-pyrrolines, respectively, in good to moderate yields.

■ Synthetic Studies of 1,2,3,4-Tetrahydro-1,3,4-trioxo-β-carboline Alkaloids I

Hideharu Suzuki, Kayoko Shinpo, Towako Yamazaki, Sachiko Niwa, Yuusaku Yokoyama, and Yasuoki Murakami

*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

A simple and efficient total synthesis of 1,2,3,4-tetrahydro-1,3,4-trioxo-β-carboline (1) was accomplished via C₃-selective acylation of indole-2-carboxylate (5). On the course of this study, we found that the cyclization of N-(2-indolecarbonyl)glycine (8a) with PPA gave only an N-cyclized 6-membered ring (10a), whereas N-(2-indolecarbonyl)-β-alanine (8b) gave a C₃-cyclized 7-membered ring (9b) as a main product.

■ Stereochemical Assignment of Pseudoindoxyl Alkaloids

Hiromitsu Takayama, Mika Kurihara, Sanan Subhadhirasakul, Mariko Kitajima, Norio Aimi, and Shin-ichiro Sakai

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

Abstract

The stereochemistries of the C2 and C3 positions in three pseudoindoxyl alkaloids, i.e., mitragynine pseudoindoxyl, yohimbine pseudoindoxyl, and β-yohimbine pseudoindoxyl, were elucidated by spectroscopic analyses. The CD spectra of these compounds and that of fluorocarpamine showed the antipodal-like curves in the long wavelength region.

■ Importance of the Hydroxymethyl-quinuclidine Fragment in the Catalytic Asymmetric Aldol Reactions Utilizing Quaternary Ammonium Fluorides Derived from Cinchona Alkaloids

Takayuki Shioiri, Akemi Bohsako, and Akira Ando

*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

Abstract

The hydroxymethyl-quinuclidine fragment in quaternary ammonium fluorides derived from cinchona alkaloids proved to play an important role on the stereochemical course in the fluoride ion catalyzed aldol reactions.

■ Synthetic Studies of Halichondrin B, an Antitumor Polyether Macrolide Isolated from a Marine Sponge 5. A Highly Concise and Efficient Synthesis of the C₃₇~C₅₄ Tricyclic JKL-Ring Part

Kiyoshi Horita, Shun-ichiro Hachiya, Kazuhito Ogihara, Yutaka Yoshida, Masaaki Nagasawa, and Osamu Yonemitsu

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

Abstract

A concise and efficient synthesis of C₃₇~C₅₄ tricyclic JKL-ring unit (2) of halichondrin B (1) utilizing C₂-symmetric spiroketal derivative (5) as a synthetic key intermediate, easily provided from dimethyl L-(+)-tartrate, is reported.

■ Halogen-Magnesium Exchange Reaction of Iodoindole Derivatives

Yoshinori Kondo, Akihiro Yoshida, Shuichiro Sato, and Takao Sakamoto

*Faculty of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan

Abstract

Halogen-magnesium exchange reaction of iodoindoles with ethylmagnesium bromide in THF undergoes smoothly to give indolylmagnesium bromides which react with various electrophiles.

■ Chiral Synthesis of Phosphodiesterase Inhibitor, (R)-(-)-Rolipram, by Means of Enantioselective Deprotonation Strategy

Toshio Honda, Fumihiro Ishikawa, Kazuo Kanai, Shigeki Sato, Daishiro Kato, and Hideo Tominaga

*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Enantioselective synthesis of the antidepressant (R)-(-)-rolipram (1) has been achieved by using an enantioselective deprotonation of the cyclobutanone derivative as a key step.

■ Short Step Synthesis of 4-Substituted Indoles Using Palladium-catalyzed C-C Bond Forming Reaction

Kazuyuki Doi and Miwako Mori

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

Abstract

Enol triflate of N-tosyl-4-oxo-tetrahydroindole (2) was a good precursor for a synthesis of 4-substituted indoles. Various functional groups were introduced to form corresponding indoles using palladium-catalyzed carbonylation and a cross-coupling reaction followed by dehydrogenation by palladium on charcoal.

■ Intramolecular Photoreaction of Thiobarbiturates with an Alkenyl Group in Their N-Side Chain. Regioselective Synthesis of Fused Pyrimidine Derivatives through Photocycloaddition of Mono- and Dithiobarbiturates¹

Haruko Takechi and Minoru Machida

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

Upon irradiation, thiobarbiturates (1 and 2) with an alkenyl group in their N-side chain give bi- and tri-cyclic fused pyrimidine derivatives through regioselective [2+2] photocycloaddition.

■ Photoreaction of Thiobenzamide with 2-Vinylfuran Analogues. Facile Synthesis of Tetracyclic Indole System

Kazuaki Oda, Hisao Tsujita, Masayuki Sakai and Minoru Machida

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

Photoreaction of thiobenzamide (1) with 2-vinylfuran analogues (2) in benzene solution gives 1H-benzo[g]furo[2,3-e]indole derivatives (3,5).

■ (S)-2-Methyl-1,5-bis(1,3-dimethyl-6-lumazinyl)-1,5-pentanedione from the Marine Polychaete, Odontosyllis undecimdonta

Hideo Tanino, Hiroyuki Takakura, Hisae Kakoi, Kunisuke Okada, and Shoji Inoue

*Faculty of Pharmacy, Meijo University, 150 Yagoto, Tempaku-ku, Nagoya, Aichi 468-8503, Japan

Abstract

(S)-2-Methyl-1,5-bis(1,3-dimethyl-6-lumazinyl)-1,5-pentanedione (3), a new metabolite of the dimeric form of 1,3-dimethyl-6-acyllumazine derivatives, was isolated from the swimming polychaete, Odontosyllis undecimdonta.

■ High Pressure Mediated Asymmetric Diels-Alder Reaction of Chiral Sulfinylacrylate Derivatives with Furan and 2-Methoxyfuran

Yoko Nakajima Yamakoshi, Wei-Ying Ge, Jun Sugita, Kazuya Okayama, Tamiko Takahashi, and Toru Koizumi

*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan

Abstract

Asymmetric Diels-Alder reaction of chid sulfinylacrylate derivatives (1 and 2) with furan (3) and 2-methoxyfuran (4) proceeded under high pressure (1.2 GPa) conditions to give endo cycloadducts (6c-f). The absolute configuration of adduct (6) was confirmed by conversion of 6e to (-)-COTC (9).

■ A New Synthesis of (-)-Mesembrine Employing Sharpless AD Reaction and New Radical-initiated Reaction

Takehiko Yoshimitsu and Kunio Ogasawara

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

Abstract

Sharpless asymmetric dihydroxylation (AD reaction) of σ-symmetric ethyl α,α-di[(E)-2-butenyl](3,4-dimethoxyphenyl)acetate allows an asymmetric construction of a quaternary carbon center by diastereoselective formation of the γ-lactone in moderate optical yields when double dihydroxylation occurs. The lactone generated is transformed into a Sceletium alkaloid (-)-mesembrine by discovery of the unprecedented radical-initiated cleavage reaction.

■ A Novel Cyclization of Electron Deficient N-Benzenesulfonyl-β-phenethylamines Using Ethyl Chloro(methylthio)acetate. Synthesis of Ethyl 1,2,3,4-Tetrahydroisoquinoline-1-carboxylates

Harumichi Kohno and Yasuo Sekine

*Lead Optimization Research Laboratory, Tanabe Seiyaku Co.Ltd., 2-2-50, Kawagishi, Toddda, Saitama 335-8505, Japan

Abstract

The reaction of electron deficient N-benzenesufonyl-β-phenethylamines (2) with ethyl chloro(methylthio)acetate (1) gave ethyl 2-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-1-carboxylates (3) in high yields. We examined the effects of a substituent on the benzene ring and several Lewis acids in this cyclization.

■ Chiral Lactams as Templates for Enzyme Inhibitors: A Simplified Route to the Expanded Pool

Ramaswamy Shankar and A. Ian Scott

*Center for Biological NMR, Department of Chemistry, Texas A & M University, College Station, Texas 77843-3255, U.S.A.

Abstract

A new class of dipeptide lactam templates first prepared using glycine phosphonates is now expanded to contain other amino acids and primary amine derivatives in a simplified general approach.

■ Nucleosides and Nucleotides. 138. Synthesis of 3-Halo-3-deazainosines: Conformational Lock with the Halogen at the 3-Position of the 3-Deazainosine in anti-Conformation

Noriaki Minakawa, Naoshi Kojima, and Akira Matsuda

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

Abstract

Synthesis of 3-chloro-, bromo-, and iodo-3-deazainosines (6-8) can be done by treatment of the 3-deazainosine derivative (2) with N-halosuccinimides. Treatment of the 5-formylimidazole derivative (11) with vinylmagnesium bromide gave 5-(1-hydroxy-2-propenyl)imidazole derivative (12), followed by fluorination and appropriate manipulations to cyclize, affording 3-fluoro-3-deazainosine (18). Although free rotation around the glycosyl linkage in 3-deazainosine (1) and 18 was observed, those of 6, 7, and 8 were rather fixed in the anti-conformation as analyzed by nOe experiments.

■ Synthesis of Tricyclic Nitrogen-containing Heterocycles by Palladium-catalyzed Cyclization of 2-Alkenyl-N-(o-iodobenzoyl)- and 2-Alkenyl-N-(o-iodophenylacetyl)pyrrolidines

Masazumi Ikeda, Susumu Akamatsu, Yasuhiro Kugo, and Tatsunori Sato

*Kyoto Pharmaceutical University, Misasagi-Shichonocho, Yamashina, Kyorto 607-8414, Japan

Abstract

The palladium-catalyzed cyclization of the 2-alkenyl-N-(o-iodobenzoyl)-and 2-alkenyl-N-(o-iodophenylacetyl)pyrrolidines gave the tricyclic nitrogencontaining heterocycles.