HETEROCYCLES

■ Preface

Shigehiko Sugasawa

*Medical Faculty, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan

■ Preface

Derek H. R. Barton

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

■ Profile and Scientific Contributions of Professor Tetsuji Kametani

Ken’ichi Takeda

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

■ Scientific Contributions of Professor Tetsuji Kametani

Keiichiro Fukumoto

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

■ Papers of Professor Tetsuji Kametani

Keiichiro Fukumoto*

*The Japan Institute of Heterocyclic Chemistry, 1-7-17, Motoakasaka, Minato-ku, Tokyo 107-0051, Japan

■ Recent Progress toward the Synthesis of Mitosenes

Julius Rebek, Jr.* and Steven Shaber

*Department of Chemistry, University of Pittsburgh, Parkman Avenue & University Drive, Pittsburgh, PA 15260 , U.S.A.

Abstract

The tricyclic ketone 1 has been converted to the mitosene 7 in nine steps. The methods described appear to offer access to mitosenes derived from natural products.

■ Novel Condensing Agents for Bischler-Napieralski Type Cyclodehydration

Sreeramulu Nagubandi* and G. Fodor

*Mayo Clinic and Mayo Foundation, Rochester, Minesota 55901, U.S.A.

Abstract

Trifluoroaceticanhydride and trifluoromethyl sulfonyl anhydride are used in Bischler-Napieralski type cyclization. Starting from the appropriate amides, the dihydroisoquinolines are formed in excellent yields.

■ Modified Crown Ether Catalysts. 4. Cleavage of Macrocyclic Ethers by Eaton’s Reagent (Methanesulfonic Acid / Phosphorous Pentoxide)

Paul E. Stott, Jerald S. Bradshaw,* and W. Wesley Parish

*Department of Chemistry, Brigham Young University, Provo, UT 84602, U.S.A.

Abstract

Eaton’s reagent (methanesulfonic acid/phosphorous pentoxide) is a superior media for the acylation of benzo crown ether compounds. Benzo-15-crown-5 was cleaved in Eaton’s reagent to form methansulfonate esters of the glycol cleavage products. A comparison of the NMR spectrum of the cleavage products with those of some of the possible products showed that the aliphatic glycols formed the major portion of the cleavage products.

■ Heterocycles IX. Asymmetric Epoxidation of a Quinone and Syntheses of Chiral Lactones

Yoshihiro Harigaya, Hiroko Yamaguchi, and Masayuki Onda*

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

Abstract

The epoxy diketone (2) is obtained in optically active form by the phase-transfer chiral epoxidation of the quinone (1). The transformation of 2 to the lactones (5) and (6) is carried out without the loss of optical activity.

■ Cyclic Tautomers of Tryptophans and Tryptamines. III. Selective 5-Hydroxylation of Tryptophan and Tryptamine Derivatives

Tohru Hino,* Mikio Taniguchi, and Masako Nakagawa

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

Abstract

The oxidation of the cyclic tautomer (5) of tryptophan derivatives with Fremy’s salt or lead tetraacetate gave p-quinoneimine derivative (6) selectively which was readily converted to 5-hydroxytryptophan derivatives on the reduction and the ring-opening.

■ Chitraline and 1-O- Methylpakistanine, Two Aporphine-Benzyliso-quinoline Alkaloids

S. Fazal Hussain, Lajber Khan and Maurice Shamma*

*Department of Chemistry, The Pennsylvania State University, York Campus, P1031 Edgecomb Avenue, York, Pennsylvania 17403, U.S.A.

Abstract

Berberis orthobotrys has yielded the new alkaloid chitraline (2) which is the first known naturally occurring analog of pakistanine (1). Another alkaloid present is 1-O-methylpakistanine (4) which had been previously derived in vitro from pakistanamine (5) through an acid catalyzed dienone-phenol rearrangement. Known alkaloids also present in the plant are pakistanamine (5) and pakistanine (1).

■ Reversible Ring Opening of 3,9-Disubstituted Adenines : Effect of Substituents

Tozo Fujii,* Tohru Saito, and Tsuyoshi Nakasaka

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

Abstract

The equilibrium constants and the rates of ring opening and cyclization for equilibria between the 3,9-disubstituted adenines IVa-1 and the N-alkylformamidoimidazoles Va-1 in H₂O at pH 8.98 and 25°C have been measured. It has been found that a bulky substituent at the 3-position of IV retards the ring opening to give V, whereas an electron-withdrawing group at the 3- or the 9-position accelerates it. A bulky alkyl group on the formamido nitrogen of V markedly retards the cyclization leading to IV, favoring the ring-opened form in the equilibrated mixture.

■ Total Synthesis of (±)-Eburnamonine and (±)-Epieburnamonine

Kunihiko Irie and Yoshio Ban*

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

Abstract

Anodic oxidation of N-carbomethoxy-3-ethylpiperidine-3-acetic acid (11) provided the corresponding lactone (12) in good yield, from which were synthesized (±)-eburnamonine and (±)-epieburnamonine by the modified procedure.

■ Reactions and Synthetic Applications of β-Keto Sulfoxides IX. Synthesis of 5-Methylthio and 5-Methoxy Analogs of Ellipticine

Yuji Oikawa, Masahide Tanaka, Hitoshi Hirasawa, and Osamu Yonemitsu*

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

Abstract

A β-keto sulfoxide (9) derived from ethyl indole-butyrate (8) and FAMSO was cyclized to a 2-keto-1,2,3,4-tetrahydrocarbazole derivative (10). After introduction of an acetic ester at the carbonyl group to give 11, its aromatization gave a 1-methylthiocarbazole (12), followed by construction of a pyridine ring to yield efficiently 5-methylthioellipticine (6). Compound 11 was quite easily hydrolyzed to a 1-keto derivative (18), which was aromatized and then converted to 5-methoxyellipticine (7).

■ Synthesis and Deuteration of Some Halogenoquinolizinium Bromides

Georgine M. Sanders,* Marinus van Dijk and Henk C. van der Plas

*Laboratory of Organic Chemistry, Agricultural University, De Dreijen 5, 6703 BC Wageningen, The Netherlands

Abstract

Syntheses and ¹H-nmr spectra are reported for the hitherto unknown 1-bromo-, 3-bromo-, 4-bromo-, 2-chloro-, 4-chloro-, 1,2-dibromo-, 3,4-dibromo- and 2,7-dibromoquinolizinium bromide. These compounds, quinolizinium bromide, 1-hydroxy-, 2-hydroxy-, 3-hydroxy-, 2-piperidino- and 2-diethylaminoquinolizinium bromide and 2- and 4-quinolizone were deuterated by heating with D₂O (Table I).

■ A Facile Synthesis of 4-Phenylthio-2(5H )-furanone Derivatives. Synthesis of Sesquirose Furan and Bullatenone

Yasuhiro Takahashi, Hisahiro Hagiwara, Hisashi Uda,* and Hiroshi Kosugi

*Chemical Research Institute of Non-Aqueous Solutions, Tohoku University, Katahira, Aoba-ku, Sendai 980-8577, Japan

Abstract

Condensation of the dianions derived from E-3-(phenylthio)-prop-2-enoic acid and its 2-methyl homologue with aldehydes and ketones provides a facile one step synthesis of 5-substituted 4-phenylthio-2(5H)-furanone derivatives. The application to the synthesis of sesquirose furan and bullatenone is described.

■ Reaction of B-(1-Alkenyl)-dialkyboranes with Isocyanates

Bakthan Singaram, Gary A. Molander and Herbert C. Brown*

*Wetherill Laboratory, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

9-(1-Alkenyl )-9-borabicyclo[3.3.1]nonanes [9-(1-alkenyl)-9-BBN], easily prepared by hydroboration of the corresponding alkynes with 9-borabicyclo[3.3.1]nonane (9-BBN), undergo remarkably facile reaction with two equivalents of isocyanates to give the intermediates (6), which on hydrolysis, provide in excellent yield N,N’-disubstituted N-(2-alkenoyl)-ureas. B-(1-Octenyl)-dicyclohexylborane reacts with aliphatic and aromatic isocyanates to furnish the novel heterocycle (11), which on hydrolysis yields N,N’-disubstituted N-(3-cyclohexylnonanyl)-ureas. B-(1-Alkenyl)disiamylboranes are inert towards isocyanates.

■ A Facile Synthesis of a Nuphar Alkaloid, Nupharolutine

Mitsutaka Natsume* and Masashi Ogawa

*Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158, Japan

Abstract

A regio- and stereoselective synthesis of (±)-nupharolutine (2) was achieved starting from 3-methylpyridine by utilizing the SnCl₂-effected reaction of endoperoxide of a 1,2-dihydropyridine derivative 5.

■ Mallotucin C and D, Two Diterpenic Lactones from Mallotus repandus

Tetsuo Nakatsu , Sho Ito,* and Takeshi Kawashima

*Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Investigation on the constituents of the titled plant collected in June resulted in the isolation of mallotucin B and mallotucins C and D (as acetates). Mallotucin A (≡teucvin), which is the only diterpenic constituent in the plant collected in December, was not detected. Structures of mallotucins C and D were elucidated on the basis of their chemical correlation with mallotucin A and the detailed spectral analyses of their acetates. Mallotucin A is suggested to be biosynthesized from chettaphane-type precursors, mallotucins B, C and/or D.

■ Preparation of 15-Oxo-16-methoxycarbonyl-15, 20-dihydrocleavamine and Coupling Reaction with Vindoline

Ratremaniaina Z. Andriamialisoa, Nicole Langlois and Yves Langlois

*Substances Naturelles du C. N. R. S, Institut de Chimie des, 91190 - Gif-sur-Yvette, France

Abstract

Several derivatives of 16-methoxycarbonyl cleavamines oxygenated in position 15 have been prepared and the coupling reaction of 15-oxo 16S-methoxycarbonyl 15,20-dihydro cleavamine with vindoline has been studied.

■ Synthesis of Adamantane Derivatives. 51. Synthesis of 2,4-Diazabridged-noradamantane, -protoadamantane, and -adamantane Derivatives via Intramolecular 1,3-Dipolar Cycloadditions

Tadashi Sasaki,* Shoji Eguchi, and Takanori Suzuki

*Department of Applied Chemistry, Faculty of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan

Abstract

N-Acyl-N’-methyl-2,4-diaza-bridged noradamantane (4), -protoadamantane (7), and -adamantane derivatives (10a,b) were obtained via intramolecular 1,3-dipolar cycloadditions of the corresponding C-bicycloalkenylazomethine imines (3, 6, 9a and 9b).

■ The C(16’) Configuration of Vincaleukoblastine-like Natural and Synthetic Substances

Ernest Wenkert,* Edward W. Hagaman, Nai-yi Wang, Gerald E. Gutowski and Jean C. Miller

*Department of Chemistry, Rice University, Houston, Texas 77251, U.S.A.

Abstract

Comparison of the ¹³C NMR spectra of a vincaleukoblastine derivative and a synthetic C(16’) epimer system yields carbon shift parameters diagnostic of the stereochemistry of the site of attachment between the indole and indoline portions of vincaleukoblastine-like substances.

■ Reductive Methylation of ω -Carbinollactams via Anomalous Witting Reaction

J. J. J. de Boer and W. N. Speckamp*

*Rothmsted Experimental Station, Harpenden, Herts, U.K.

Abstract

Methylene phosphorane reacts with carbinollactams 4 with unexpected formation of 5-Me-substituted lactams 5. Reaction of phosphorane homologs with 4 afforded the γ,δ-alkenylamides 6.

■ A New Synthesis of 3(2H )-Furanones from Ketones

Tamejiro Hiyama,* Masaki Shinoda, Hiroyuki Saimoto, and Hitosi Nozaki

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

Abstract

Ketones are allowed to react with the lithium salt of propynal diethyl acetal and the resulting adducts are treated with sulfuric acid-methanol (1:1) to give the title compounds.

■ Ring Transformations of 6H-Cyclopropa[5a,6a]pyrazolo[1,5-a]pyrimidine

Takushi Kurihara,* Tsutomu Tani, and Keiko Nasu

*Faculty of Pharmaceutical Science, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

The ring transformations of 5a-acetyl-6a-carbethoxy-5a,6a-dihydro-6H-cyclopropa[5a,6a]pyrazolo[1,5-a]pyrimidine-3-carbonitrile (2) and the corresponding 5-methyl derivative (3) into pyrazolylpyrroles (7 and 8), pyrazolopyrimidine (10), and pyrazolylpyridone (12) under the basic, acidic, and neutral condition are described.

■ Synthesis and X-Ray Crystal Structure of A (C₂)-Dioxatrisecododecahedrane

Leo A. Paquette,* Douglas Balogh, and Peter Engel*

*Evans Chemical Laboratories, The Ohio State University, 120 W. 18th Avenue, Columbus, Ohio 43210, U.S.A.

Abstract

A trisecododecahedrane in which two oxygen atoms have replaced a pair of methylene groups at sites of high steric congestion has been prepared with crystalline features suitable for x-ray analysis. The complete structure of the molecule which reveals its topology is reported.

■ Reaction of 1-Methyl-2-(methylthio)-quinolinium lodide with Active Methylene Compounds

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

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

Abstract

1-Methyl-2-(methylthio)quinolinium iodide (I) reacted with active methylene compounds (IIa-f) in the presence of sodium hydride to give 1,2-dihydro-1-methyl-2-(substitutedmethylene)-quinolines (IIIa-f) in almost quantitative yields.

■ The Remarkably Facile Rearrangement of a 2,3,5,6-Tetraketopiperazine to 4,5-Dioxoimidazolidine-2-carboxylic Acid Derivatives and Its Reversal

John H. Hoare and Peter Yates*

*Biochemical Institute, University of Ghent, Ledeganckstraat, Ghent, Belgium

Abstract

Reaction of N,N’-dibenzyl-2,3,5,6-piperazinetetraone (1) with boiling ethanol gives ethyl N,N’-dibenzyl-4,5-dioxoimidazolidine-2-carboxylate (2a). Analogous rearrangement products are formed with methyl, n-propyl, n-butyl, and isopropyl alcohols, and ethylene glycol. In the last case the cleavage product N,N’-dibenzyloxamide is also formed. Thermolysis of 2a results in loss of ethanol and regeneration of 1.

■ A New Synthesis of Fervenulins and Alloxazines. Thermolysis and Photolysis of 6-Azido-1,3-dimethyluracil with Tetrazoles and Benzotriazoles

Kosaku Hirota, Kazuo Maruhashi, Tetsuji Asao, and Shigeo Senda*

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

Abstract

Thermolysis of 6-azido-1,3-dimethyluracil (1) in the presence of 5-substituted tetrazoles (2) gave 3-substituted fervenulins (4), which were also synthesized from the intermediates (3) prepared by photolysis of (1) with (2). Irradiation of (1) with benzotriazoles (6) in tetrahydrofuran gave 6-(benzotriazol-1-yl)uracils (7), which were irradiated in methanol to afford alloxazines (8).

■ Cycloaddition Reaction of 5-Formyl-1,3,6-trimethyluracil with Aldehydes. New Synthetic Approach to Pyrano[4,3-d ]pyeimidines

Kosaku Hirota, Tetsuji Asao, Isao Sugiyama, and Shigeo Senda*

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

Abstract

A new synthetic approach to pyrano[4,3-d]pyrimidine derivatives is described. Reaction of 5-formyl-1,3,6-trimethyluracil with aldehydes in the presence of lithium diisopropylamide affords pyrano[4,3-d]pyrimidines via a dienol intermediate.