HETEROCYCLES

■ A Perspective on the Contributions to Heterocyclic Chemistry by Professor Edward C. Taylor of Princeton University

Peter A. Jacobi and Stephen F. Martin

*Department of Chemistry, Wesleyan University, Middletown, Connecicut 06459-0180, U.S.A.

■ Regioselective Synthesis of Maturone via Lewis Acid Catalyzed Deils-Alder Reaction

Mariko Aso, Akio Ojida, Guang Yang, and Ken Kanematsu*

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

Abstract

Total synthesis of maturone (1) by the regioselective Diels-Alder reaction of benzofuranquinone (7) is described. Compound (7) was easily obtained by an application of the fused furan constructing method using allenic sulfonium salt (3) and cyclic 1,3-dicarbonyl compound.

■ Diels-Alder Cycloaddition of 2(1H)-Pyridones Having Two Electron-Withdrawing Groups with Electron Deficient Dienophile

Hiroto Nakano and Hiroshi Hongo*

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

Abstract

The first examples are presented of Diels-Alder cycloadditions of 2(1H)-pyridones having two electron-withdrawing groups on the ring, with electron deficient dienophiles, and the adducts obtained may act as dienophiles leading to richly functionalized, bridged, and polycyclic azacompounds, under high pressure conditions.

■ Reaction of Lithum Trimethylsilydiazomethane with β-Amino-α,β-unsaturated Ketones

Tatsuya ito, Keiichiro Hatano, Yukihisa Kurono, Toyohiko Aoyama, and Takayuki Shioiri*

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

Abstract

Reaction of lithium trimethylsilyldiazomethane with various β-morpholino- (and piperidino)-α,β-unsaturated ketones gives 3- (or 5)-acylpyrazoles, while the reaction with β-pyrrolidino derivatives mainly affords 1,2-diazabicyclo[3.2.0]hepta-2,6-dienes.

■ A Facile Route to Tetrahydroisoquinoline Alkaloids via Sulfoxide Mediated Cyclization

Seiichi Takano,＊ Hirokazu Iida, Kohei Inomata, and Kunio Ogasawara

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

Abstract

A facile route to 1,2,3,4-tetrahydroisquinoline framework has been developed by employing the sulfoxide mediated cyclization reaction. Utilizing the reaction developed some naturally occurring isoquinoline alkaloids have been synthesized.

■ Photochemical Synthesis and Electrochemical Behavior of Triphenyleno[4,5-bcd]thiophene and Triphenyleno[4,5-bcd]selenophene Derivatives

Takeshi Kimura, Yasuhiro Ishikawa, and Naomichi Furukawa*

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

Abstract

Photolysis of 1,9-bis(arylthio)dibenzothiophene afforded triphenyleno[4,5-bcd]thiophene and tribenzo[bc,e,hi][2,7]dithiaazulene derivatives. Deuterium tracer experiment revealed that this reaction proceeded intramolecularly.

■ Synthesis of 2-Substituted Furan-annulated 3-Sulfolenes and Their Diels-Alder Reactions

Takayoshi Suzuki, Hideyuki Fuchii, and Hiroaki Takayama*

*Faculty of Pharmaceutical Sciences,Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan

Abstract

The preparation of 2-substituted 4,6-dihydrothieno[3,4-c]furan-5,5-dioxides (1b-e) and their intermolecular Diels-Alder reactions with typical dienophiles are described.

■ Regioselectivity in the 1,3-Dipolar Cycloaddition Reaction of Diazomethane to 7-Oxanorbornene Derivatives

Odón Arjona,* Cristina Manzano, and Joaquín Plumet*

*Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense de Madrid, Ciudad Universitaria, E-28040 Madrid, Spain

Abstract

The regioselectivity of the 1,3-dipolar cycloaddition reaction of diazomethane to 7-oxabicyclo[2.2.l]hept-5-ene derivatives substituted on C-2 is discussed. The observed ratio of regioisomers depends upon the nature of the substituents on C-2 and may be accounted for in terms of TS asyncrony for concerted processes.

■ Preparation and Properties of Bis[1,2,5]thiadiazolotetrathiafulvalene

Masaaki Tomura, Shoji Tanaka, and Yoshiro Yamashita*

*Institute for Molecular Science, Nishi-Gonaka 38, Myodaiji, Okazaki 444-8585, Japan

Abstract

Bis[1,2,5]thiadiazolotetrathiafulvalene (1) was prepared by desulfurization of the corresponding 1,3-dithiole-2-thione (2) with triphenylphosphine. It showed relatively high oxidation potentials due to the electron-withdrawing thiadiazole ring. The X-ray structural analysis revealed that there exist short intermolecular S---S and S---N contacts in the crystal.

■ The Lewis Acid-catalyzed Intramolecular Asymmetric Hetero Diels-Alder Reaction of Chiral α'-Sulfinyl-α,β-unsaturated Ketone. A Chiral Diene Bearing an Optically Active Sulfinylmethyl Group

Kunio Hiroi,* Masayuki Umemura, and Yoko Tomikawa

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

Abstract

This paper presents an asymmetric Diels-Alder reaction with a diene bearing a chiral sulfinyl group. The Lewis acid-catalyzed intramolecular asymmetric hetero Diels-Alder reaction of a chiral α’-sulfinyl-α,β-unsaturated ketone derived from ˙3-methylcitronellal produced optically active 4a,5,6,7,8,8a-hexahydro-1H-2-benzopyran derivatives. On the basis of the stereochemical results obtained, a plausible mechanism for the asymmetric induction is presented.

■ Novel Cyclopentadieno-1,3-dithiols

Klaus Hartke* and Carsten Timpe

*Institut für Pharmazeutische Chemie, Universität Marburg, Marbacher Weg 6, D-35032 Marburg/Lahn, Germany

Abstract

The synthesis of 5-methylcyclopentadieno-1,3-dithiol-2-thione (16) and some related reactions are described.

■ Synthetic Approaches to 11-Hydroxycephalotaxine

Masazumi Ikeda,* Keigo Kosaka, Minoru Sakakibara, and Masahiko Okano

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

Abstract

Several approaches to functionalize the cephalotaxine skeleton based on the Pummerer reaction and Moriarty oxidation are described.

■ Synthetic Studies on the Narciclasine Alkaloids. A Synthesis of (±)-Lycoricidine

Stephen F. Martin* and Hsi-Hwa Tso

*Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712-1074, U.S.A.

Abstract

The hetero Diels-Alder reaction of benzyl nitrosocarbamate with the diene (10) and the Heck cyclization of the derived amide (14) served as the key steps in a concise synthesis of (±)-lycoricidine (1).

■ Sequential C-2 Lithiation/Acylation of N-1 Functionalized Imidazoles: Synthesis of Novel Tetrahydroimidazo[1,2-a][1,4]diazepines

William J. Hoekstra* and Jeffery B. Press

*The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477, U.S.A.

Abstract

5,6,7,9-Tetrahydroimidazo[1,2-a][1,4]diazepines (4a-c) are prepared by conversion of 2-acylimidazoles (2a-c) to cyclic imines (3a-c) followed by hydride reduction. In the key step, a masked primary amine (1) is acylated in good yield employing an alkyllithium base to afford acylimidazoles (2a-c) after acid hydrolysis of the imines. This reaction avoids use of transient N-1 (im) protecting groups.

■ General Routes to 4-Oxo-4H-pyrano[2,3-b]pyridine-3-carboxylates and Related Compounds: Synthesis of the Oxygen and Sulfur Isosteres of Nalidixic Acid

Stuart W. McCombie,* Sue-Ing Lin, and Jayaram R. Tagat

*Chemical Research, Schering-Plogh Research Institute, DDF 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, U.S.A.

Abstract

lmidazolides of 2-hydroxy- and 2-mercaptonicotinic acids with LiCH₂CO₂Bu-t gave ketoesters which were cyclised with MeOCH=NMe₂⁺ MeOSO₃^- and i-Pr₂NEt or with (RCO)₂O-NEt₃-DMAP to the title 2-H or 2-R bicyclic esters; the corresponding 3-methylsulfonyl and 3-phosphonate analogs were similarly prepared. The 2-unsubstituted 4-oxopyranopyridine-3-carboxylates were unstable at physiological pH, whereas the thio analogs were stable.

■ Introduction of Nucleophiles or Ethyl Group to the Indole Nucleus through Nucleophilic Substitution and/or Radical Reactions of 1-Methoxyindole-3- and -2-carboxaldehyde

Fumio Yamada, Yashikazu Fukui, Daisuke Shinmyo, and Masanori Somei*

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

Abstract

1-Methoxyindole-3- and -2-carboxaldehyde were found to undergo nucleophilic substitution and radical reactions resulting in the introduction of nucleophiles and/or ethyl group at the 2- or 3-position.

■ Facile Synthesis of Optically Active Sulfonates of 4-tert-Butoxycarbonyl-2-hydroxynethylmorpholine

Hiroaki Yanagisawa* and Takuro Kanazaki

*Research Institute, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

Abstract

Optically active sulfonates of 4-tert-butoxycarbonyl-2-hydroxymethylmorpholine were prepared from 1,2:5,6-di-O-D-mannitol by practical procedures. These compounds are versatile intermediates for optically active isomers of a number of neuropharmacologically or gastrokinetically active agents that have a 2-morpholinylmethyl group.

■ Aspects of the Intramolecular Diels-Alder Reactions of Some 1,3,8-Trienic Esters

Masahiro Toyota, Yoshihiro Wada, and Keiichiro Fukumoto*

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

Abstract

The intramolecular cycloadditions of a number of 1,3,8-trienes containing monoester or diester function were examined. The unsaturated ester (4) gave the unexpected dimeric lactone (10) in the absence and presence of Et₂AICI. On the other hand, the thermolyses of the triene mono- and diesters (6) and (9) in the presence of Lewis acid afforded mixtures of the corresponding cycloadducts and those epimers (16) and (23) respectively.

■ Synthesis of Potential Transition State Inhibitors of Succinyl CoA: Tetrahydrodipicolinate N-Succinyltransferase

John L. Roberts,* Jack Borgese, Cecil Chan, Dennis D. Keith, and Chung-Chen Wei

*Roche Research Center, Hoffmann-La roche, Inc., 340 Kingsland Street, Nutley, New Jersey 07110, U.S.A.

Abstract

The preparation of 2-hydroxytetrahydropyran-2,6-dicarboxylic acid (6S-1), 2-hydroxytetrahydrofuran-2,5-dicarboxylic acid (17), and 3,3-difluoro-2-hydroxytetrahydropyran-2,6-dicarboxylic acid (26), three transition state analogs of hydrated tetrahydrodipicolinic acid (THDPA) and a depsipeptide derivative (11) of 6S-1 is described.

■ Preparation of a Model System for a Constrained Angiotensin II Receptor Antagonist

Diane H. Boschelli* and David T. Conner

*Department of Medical Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI 48015-2430, U.S.A.

Abstract

An imidazo[5,1-c][1,4]oxazin-8-one system, designed to be a fused ring analog of a potent angiotensin II receptor antagonist, was prepared.

■ A Novel Neuroexcitatory Amino Acid from Clitocybe acromelalga. A Possible Interamediate in the Biogenesis of Acromelic Acid A

Kimiaki Yamano, Katsuhiro Konno, and Haruhisa Shirahama*

*Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan

Abstract

A new neuroexcitatory amino acid, L-3-(6-carboxy-2-oxo-3-pyridyl)alanine (7), was isolated from the poisonous mushroom Clitocybe acromelalga and its structure was confirmed by chemical conversion. Its occurrence in this fungus supports the previously proposed biogenesis of acromelic acid A.

■ Aqueous Diels-Alder Reactions of Electron Deficient 2-Arylfurans: A Highly Stereoselective Route to 2,2,5-Trisubstituted Tetrahydrofurans towards a Novel Class of Orally Active Azole Antifungals

Anil K. Saksena,* Viyyoor M. Girijavallabhan, Yao-Tsung Chen, Edwin Jao, Russell E. Pike, Jagdish A. Desai, Dinanath Rane, and Ashit K. Ganguly

*Schering-Plogh Research Institute, DDF 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, U.S.A.

Abstract

Aqueous Diels-Alder reactions¹ of halogenated 2-arylfurans with acetylenedicarboxylates made available previously inaccessible adducts (2, 2a, 7, and 8) which were successfully elaborated in a general stereocontrolled route to the title compounds.

■ Gelsemine Model Studies: Alkoxymethylations of Decalones and Indoles

David J. Hart* and Shung C. Wu

*Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, U.S.A.

Abstract

Treatment of decalone (11) with acetone or dimethoxymethane and an appropriate acid gave tetrahydropyrans (10) (74%) and (13) (59%), respectively. Similar treatment of indole (6) with dimethoxymethane gave indoline (14) (59%). Attempts to effect similar reactions with indole (4) were unsuccessful.

■ Synthesis of Potentially Useful Intermediates for 1-Fluorocarbapenems

Masataka Ihara, Ken Satoh, Nobuaki Taniguchi, Keiichiro Fukumoto,* Yohhei Inaba, and Makoto Takemura

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

Abstract

The displacement reaction of the 4-acetoxyazetidin-2-one (6) with dimethyl fluoromalonate was readily performed in the presence of lithium hexamethyldisilazide. The product (7), quantitatively obtained, was converted into two potential synthetic intermediates (4) and (5) of 1-fluorocarbapenem derivatives.

■ A Synthetic Approach to the Marine Sponge Alkaloids Agelasimine A and Agelasimine B

Tohru Saito, Jun Chikazawa, Yuko Nakamura, and Tozo Fujii*

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

Abstract

Syntheses of 7-benzyl-N⁶,3-dimethyladenine (1b) and 7-benzyl-1,2-dihydro-1,3-dimethyladenine (2b), selected as models for the marine sponge alkaloids agelasimine A (1a) and agelasimine B (2a), respectively, have been achieved via four-step routes starting from 3-methyladenine (7). The key steps involved are regioselective methylations of 7-benzyl-3-methyladenine (9) and 7-benzyl-1,2-dihydro-3-methyladenine (11).

■ A New Hexagonal Cyclic Enol Phosphate of 6-β-Hydroxypropionyllumazines from the Marine Swimming Polychaete, Odontosyllis undecimdonta

Shoji Inoue,* Kunisuke Okada, Hideo Tanino, and Hisae Kakoi

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

Abstract

A new hexagonal cyclic enol phosphate of 6-β-hydroxypropionyllumazine and its 3-methyl and 1,3-dimethyl derivatives were isolated from Odontosyllis undecimdonta.

■ Regioselective ortho-Lithiation of Halopyridines. Syntheses of ortho-Disubstituted Pyridines and a Convenient Generations of 3,4-Pyridyne

Gordon W. Gribble* and mark G. Saulnier

*Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03775, U.S.A.

Abstract

The regioselective ortho-lithiation of 3-chloro- (4), 3-fluoro- (7), 3-bromo- (10), 2-chloro- (22), and 4-chloropyridine (25) with lithium diisopropylamide affords, after quenching with various electrophiles, the corresponding ortho-disubstituted pyridines in yields from 16-96%. Halogen-metal exchange between 4-iodo-3-chloropyridine (6a) and tert-butyllithium or n-butyllithium provides a convenient generation of 3,4-pyridyne (1), which is trapped in a Diels-Alder reaction with furan and 2,5-dimethylfuran to give 31 and 32 (24-38%).

■ Long Range Transmission of Polar Effects in Cholinergic 3-Arylideneanabaseines. Conformations Calculated by Molecular Modelling

John A. Zoltewicz,* Katalin Prokai-Tatrai, Linda B. Bloom, and William R. Kem

*Department of Chemistry, University of Florida, Gainesville, FL 32611-2046, U.S.A.

Abstract

Benzylidene products resulting from acid-catalyzed aldol condensations of aryl aldehydes and anabaseine at position 3 of the tetrahydropyridine ring have E stereochemistry. In spite of a chemical shift scale ranging only over 0.11 ppm the methylene protons (H-6) adjacent to the imino group of the tetrahydropyridine ring show an excellent Hammett correlation using σ_M and σ_P values. Methoxy and chloro groups in an ortho position require a σ_I parameter. Substrates with one or two ortho methyl groups deviate. AM1 and MM2 calculations indicate that both the phenyl and pyridyl rings are twisted out of a common plane defined by the central ring.

■ Heterocyclic Tertiary Amines as Initiators for Haloaldehyde Oligomerization

Jan Bartus, Koichi Hatada, and Otto Vogl*

*Polytechnic University, Six MetroTech Center, Brooklyn, NY 11201, U.S.A.

Abstract

Heterocyclic tertiary amines, such as pyridine, strychnine, sparteine, nicotine, cinchonine, cinchonidine, quinine and quinidine were found to be excellent initiators for the oligomerization of chloral and bromal. Treatment of the chloral oligomer mixture with acetic anhydride gave symmetrical chloral oligomer diacetates. Sparteine initiation of bromal gave bromal oligomer diacetates.

■ Synthesis and Reactions of 4-(α-Aminoarylidene)thiazetidine 1,1-Dioxides

Herbert Plagge and Hans-Hartwig Otto*

*Pharmazeutisches Institut, LS Pharmazeutische Chemie, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Str. 9 D-7800 Freiburg i.Br., Germany

Abstract

β-Sultams react as highly potent sulfonyl analogues of β-lactams with aromatic nitriles to the title compounds (2). Hydrolysis, reduction, and reactions of 2 with acylating and alkylating agents are described. Some of the compounds show a week β-lactamase inhibition.