HETEROCYCLES

■ A Novel Synthesis of Isoquinoline Derivatives

Hideki Kato, Reiko Fujita, Hiroshi Hongo, and Hiroshi Tomisawa*

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

Abstract

Reaction of 4-cyano-1-methyl-2(1H)-pyridone (Ia) wlth 2,3-dimethyl-1,3-butadiene (II) at 170° gave cis-4a-cyano-4a,5,8,8a-tetrahydro-2,6,7-trimethyl-1(2H)-isoquinolone (IIIa) in a good yield and at 190° gave IIIa, trans-4a-cyano-4a,5,8,8a-tetrahydro-2,6,7-trimethyl-1(2H)-isoquinolone (IVa), and 2,6,7-trimethyl-1(2H)-isoquinolone (V). Heating of 4-methoxycarbonyl-1-methyl-2(1H)-pyridone (Ib) with II gave cis-4a,5,8,8a-tetrahydro-4a-methoxycarbonyl-2,6,7-trimethyl-1(2H)-isoquinolone (IIIb) in a high yield.

■ 1,3-Dipolar Cycloreversions of Isoxazolidines and Pyrazolidines

Remo Gandolfi,* Lucio Toma, and Carlo De Micheli

*Dipartamento di Chimica Organica, Università di Pavia, V. le Taramelli 10, 27100 Pavia, Italy

Abstract

1,3-Dipolar cycloreversion reactions of the adducts of 3,4-dihydroisoquinoline-N-oxide and of 3,4-dihydroisoquinoline-N-phenylimine with cyclic α,β-unsaturated ketones and their ethylene ketals were investigated. The easier fragmentation of the adducts with α,β-unsaturated ketones compared with that of the corresponding ketals can be explained on the basis of conjugation gain in the cycloreversion transition state of the former compounds.

■ Benzophenanthridinium Salt Equilibria

Mary A. Caolo and Frank R. Stermitz*

*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.

Abstract

The iminium ion alkanolamine equilibrium position has been determined in various ethanol-buffer mixtures for a number of biologically-active benzophenanthridinium salts. Iminium ion concentration of antitumor active compounds is 90% or higher in 50% EtOH-buffer but much lower (usually 10% or less) for most antitumor inactive compounds.

■ Optical Properties of C_α Oxy-substituted δ-Lactones

Zoltan Djarmati* and Miroslav Gasic

*Institute of Technology and Agriculture of IPK “Servo Mihalj”
, 23000 Zrenjanin, Serbia and Montenegro

Abstract

The CD curves of steroidal and terpenoid δ-lactones, deoxyandrololactone, and its C-16 epimeric acetoxy and hydroxy derivatives, and ambreinolide and its C-12 epimeric acetoxy derivatives, have been measured by conventional technique. The spectra are analyzed in terms of earlier investigations in the steroid and terpene series using empirical correlations.

■ Photochemical Cyanation of Quinolines and Isoquinolines. Participation of Enhanced Basicity in Excited Singlet States

Naganori Numao and Osamu Yonemitsu*

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

Abstract

When 7-methoxyquinoline and excess NaCN in aqueous MeCN was irradiated with a 100 W high pressure mercury lamp under bubbling O₂ for 3.5 hr to give 8-cyano-7-methoxyquinoline in 39% yield, whereas quinoline was recovered unchanged under similar conditions. 6-Methoxyquinoline was more reactive and gave 5-cyano-6- methoxyquinoline in 48% yield after irradiation for 1.5 hr. Isoquinoline gave 3-cyanoisoquinoline only in 11% yield, while 6- and 7-methoxyisoquinolines gave 5-cyano-6-methoxyisoquinoline (12%) and 8-cyano-7-methoxyisoquinoline (38%), respectively. The mechanism involving the participation of excited singlet state pKa was elucidated on the basis of quantum yield measurements for disappearance of 6- and 7-methoxyquinolines and for formation of the products and their pH dependence.

■ Synthesis of 9-Deoxy-9-ethoxycarbonyl-9-azaprostaglandin E₂ Ethyl Ester

Gerard P. Rozing, Johannes Kip, Willem Edam, Henk de Koning,* and Henderikus O. Huisman

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

Abstract

9-Deoxy-9-ethoxycarbonyl-9-azaprostaglandin E₂ ethyl ester 1 and its C₁₅-epimer 2 were synthesized from the readily available protected triol 3 by selective deprotection of successive hydroxyl functions and subsequent side chain construction.

■ Bicyclo[3.3.1]nonanes as Synthetic Intermediates VI. An Oxaadamantanol Intermediate which Functions in the Highly Chemoselective Ring-enlargement of Bicyclo[3.3.1]nonane-3,7-dione by Diazomethane

Takefumi Momose,* Isamu Muraoka, and Shohgo Atarashi

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

Abstract

The chemoselective synthesis of bicyclo[4.3.1]decane-3,8-dione (3) and 8-hydroxytricyclo [4.3.1.0^3,8]decan-4-one (4) from bicyclo[3.3.1]nonane-3,7-dione (1) is described. Formation of an oxaadamantanol intermediate was shown to conduct the reaction and to realize its high chemoselectivity, because the monoketone bicyclo[3.3.1]nonan-3-one (5) failed to react with diazomethane.

■ Site-specificity in the Baeyer-Villiger Oxidation of 2-Alkyl-9-azabicyclo[3.3.1]nonane-3,7-diones: Exclusive Cleavage of the Alkylated Half of the Twin-piperidinone System

Takefumi Momose,* Shohgo Atarashi, and Conrad Hans Eugster

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

Abstract

The Baeyer-Villiger oxidation of 2-alkyl-N-methoxycarbonyl-9-azabicyclo[3.3.1]nonane-3,7-diones (9a and 9b) proceeded site-specifically to afford the keto lactones (11a and 11b) which were transformed into the cis-2.6-disubstituted piperidines related to palustramic acid.

■ An Unusual Synthetic Route to Mesoionic Pyrimidines

Frank Mercer, Louis Hernandez, Jr., and Harold W. Moore*

*Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616-5295, U.S.A.

Abstract

A new and novel synthetic route to the rare mesoionic pyrimidines is described. This involves the cycloaddition of formimidates to 1,4-dipolar zwitterions. The zwitterions themselves are generated from three independent pathways, i.e., 1) the thermolysis of 4-azido-2-pyrrolinones, 2) the thermolysis of 3-cyano-2-azetidinones, and 3) from the cycloaddition of chlorocyanoketene to formimidates.

■ Reactions of α- and γ-Alkyl Groups in Pyrylium Salts and Some Transformations Reaction Products

Valery Vladimirovich Mezheritskii,* Anna L‘vovna Wasserman, and Gennady Nikolaevich Dorofeenko

*Institute of Physical Organic Chemistry, Restov-on-Don State University, Restov-on-Don, U. S. S. R.

Abstract

Pyrylium salts having π-electronic sextet and delocalized positive charge represent the particular class of aromatic compounds showing high reactivity. They are widely applied in organic syntheses and, on the other hand, are the naturally occurring plant compounds. This is why the chemistry of pyrylium salts has received a great deal of attention. This review will be generally confined to a discussion of certain reactions of pyrylium salts.

■ Dimensional Probes of Enzyme Binding Sites: Synthesis and Biological Activity

Nelson J. Leonard*

*Roger Adams Laboratory, School of Chemical Sciences, University of Illinois, 1209 West California Street, Urbana, IL 61801-3731, U.S.A.

■ Reactions of Singlet Oxygen with Heterocyclic Systems

Harry H. Wasserman*

*Department of Chemistry, Yale University, P.O. Box 6666, New Haven, Connecticut 06511, U.S.A.

■ Selective Ozonation of N-Substituted Aziridines

Yoshikatsu Ito,* Hisao Ida, Hiroaki Yokoya, and Teruo Matsuura

*Department of Synthetic Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

■ Formation of Six-membered Rings by Thermal Isomerization of 2H-Azirines: Formation of Enamines and Their Reactions

Kazuaki Isomura,* Tatsuyoshi Tanaka, Shin-ichi Noguchi, Masumi Saruwatari, and Hiroshi Taniguchi

*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

■ Reactions of 1,2-Diaryl-1-azaspiro[2.2]pentanes and 2-Phenyl-1-azaspiro[2.2]pent-1-ene with Nitrilimines

Hiroyuki Watanabe, Yoko Kiryu, and Otohiko Tsuge*

*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

■ A Synthetic Application of β-Lactam to Heterocyclic Compounds

Shinzo Kano,* Tsutomu Ebata, and Shiroshi Shibuya

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

■ Cyclization Reactions of Phenol- and Enolacetylene Compounds

Makoto Yamamoto*

*Department of Chemistry, Faculty of Science and Engineering, Saga University, Honjo 1, Saga, Saga 840-8502, Japan

■ The Structure of New Lignan, Lappaols

Akitami Ichihara,* Kengo Oda, Yoshiaki Numata, Yoshihiko Terayama, Seiji Kanai, Yasuji Nakamura, Hirokazu Kawagishi, and Sadao Sakamura

*Department of Agricultural Chemistry, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

■ Total Synthesis and Some Chemical Reactions of Bikaverin

Tetsuzo Kato,* Masayuki Sato, Nobuya Katagiri, Toshikazu Awaji, and Jun Nakano

*Abel Distinguished Service Professor, Department of Pharmacology and Molecular Sciences, Johns Hopkins University, 725 North Wolfe Street, Baltimore, MD 21205, U.S.A.

■ Total Synthesis of 16-Oxa-D-homoestrogens and Determination of the Ring Stereochemistry

Tadao Terasawa* and Toshihiko Okada

*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan

■ Fischer Indolization of Phenylhydrazones Having a Various Substituent at the Ortho Position

Hisashi Ishii, Hideko Atoda (Née Tatsuno), Toshiaki Tojo, Yoko Kondo, and Yasuoki Murakami*

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

■ A Facile and Convenient Synthetic Route to 4-Substituted Indoles

Masanori Somei,* Kazuhiko Hashiba, Fumio Yamada, and Chikara Kaneko

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

■ Synthesis and Reactions of Cyclic Tautomers of Tryptamines and Tryptohans. Behaviour of Indoles in Acidic Media

Tohru Hino,* Mikio Taniguchi, and Akinori Gonsho

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

■ Syntheses of Heterocycles by the Use of Cyclopropenium Ion as a Starting Material

Shigeo Yoneda, Hideo Hirai, Toshihisa Kato, Akihide Onoda, Yoshio Katsuro, and Zen-ichi Yoshida*

*Faculty of Engineering, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

■ Heterocycle Synthesis Using o-Methylphenyl Isocyanide

Yoshihiko Ito,* Kazuhiro Kobayashi, and Takeo Saegusa

*Department of Synthetic Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

■ Synthesis of Polycyclic Indoles by Intramolecular Ring-closure of 1- and 3-Benzoylindoles by Palladium Acetate

Toshio Itahara* and Tsutomu Sakakibara

*Department of Bioengineering, Faculty of Engineering, Kagoshima University, Korimoto, Kagoshima 890-0065, Japan

■ Syntheses of Heterocyclic Compounds via Intramolecular Benzyne Reaction and Photolysis of N-Substituted Enaminones

Yoshifumi Yuasa,* Chihiro Kibayashi, and Hideo Iida

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

■ Reactions of Aminoquinones, Synthetic Approaches to Mitomycins

Mitsuo Akiba,* Yoshiyuki Kosugi, and Toyozo Takada

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

■ New Synthetic Studies on Mitomycins

Takeshi Ohnuma,* Yasuo Sekine, and Yoshio Ban

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

■ Transformation of Indole Alkaloids: Partial Synthesis of Aricine, Reserpinine and Deserpidine

Shin-ichiro Sakai,* Norio Aimi, Junji Endo, Masato Shimizu, Etsuji Yamanaka, Masaki Ogawa, Kiyoaki Katano, Mari Kashiwazaki, Morio Fujiu, and Yoshikuni Yamamoto

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