HETEROCYCLES

■ Preface

Sankichi Takei

*,

■ Profile of Professor Dr. Adolf Butenandt

Peter Karlson

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

■ A Novel Ring Transformation of Benzothiazoline Sulfoxides

Mikio Hori,* Tadashi Kataoka, Hiroshi Shimizu, and Yutaka Imai

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

Abstract

Reaction of 3-acetylbenzothiazoline sulfoxides with acetic anhydride gave novel ring expansion products, benzothiazine derivatives.

■ Oxidation of 1-Substituted 3-tert -Butyl- and 3-Isopropylpyridinium Salts by Ferricyanide Ion

Tozo Fujii,* Takashi Hiraga, Sigeyuki Yoshifuji, Masashi Ohba, and Kiyoshi Yoshida

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

Abstract

In the alkaline ferricyanide oxidation at 32 °C of 3-substituted 1-methylpyridinium ions (type IV), the isopropyl and the tert-butyl groups at the 3-position have been found to orient the oxidation to both the 2- (type V) and the 6-position (type VI) in ratios of 71 : 29 and 14 : 86. In the oxidation of the 3-tert-butyl derivative (IVi), replacement of the N-methyl group by the 3,4-dimethoxyphenethyl group resulted in the exclusive oxidation at the 6-position, suggesting the highest degree of steric hindrance to the approach of bulky ferricyanide ion to the 2-position.

■ Volatile Components of Ledum palustre var. nipponicum et yesoense

Yoko Naya,* Yoko Nagahama, and the late Munio Kotake

*The Institute of Food Chemistry, The Institute of Food Chemistry

Abstract

Volatile components of Ledum polustre var. nipponicum et yesoesre Nakai were investigated and found to consist of more than fifty compounds. The major compound was found to be ascaridol, which is well known to exhibit antibiotic properties.

■ O-Phenylation 6-Amino-5-nitroso-1,3-dimethyluracil with Diphenyliodonium Chloride. A New Route to Lumazines

Edward C. Taylor* and Muthiah Inbasekaran

*Department of Chemistry, Princeton University , Princeton, New Jersey 08544, U.S.A.

Abstract

Treatment of 6-amino-5-nitroso-l,3-dimethyluracil (1, R = H) with diphenyliodonium chloride resulted in O-phenylation to give a quantitative yield of 6-imino-5-phenoxy-1,3-dimethyluracil (5, whose structure was established by both spectral and chemical means. Reaction of 5 with 1-morpholino-1-cyclohexene gave 1,3-dimethyl-2,4(1H,3H)-cyclohexa(g)pteridinedione (9), while reaction with 1-morpholino-1-butene gave 6-ethyl-1,3-dimethyllumazine (10).

■ Base-catalyzed Ring Contraction of 6-Imino-5-pheoxyimino-1,3-dimethyluracil to 4,5-Diimino-1,3-dimethylimidazolidin-2(1H)-one. A New Synthesis of Imidazopyrazines

Edward C. Taylor* and Muthiah Inbasekaran

*Department of Chemistry, Princeton University , Princeton, New Jersey 08544, U.S.A.

Abstract

Treatment of 6-imino-5-phenoxyimino-1,3-dimethyluracil either with morpholine or with aqueous base resulted in smooth ring contraction to give 4,5-diimino-1,3-dimethylimidazolidin-2(1H)-one (3). Condensation of 3 with o-phenylenediamine, 2,3-diaminopyridine, 5,6-diamino-1,3-dimethyluracil, and 2,4,5,6-tetraaminopyrimidine gave the condensed imidazopyrazine derivatives 4, 8, 9, and 10 respectively.

■ Sudachiin A, a New Flavone Glucoside from Sudachi

Tokunaru Horie,* Mitsuru Nakayama, Shuichi Hayashi, Masao Tsukayama, and Mitsuo Masumura

*Faculty of Engineering, University of Tokushima, Minamijosanjima-cho, Tokushima 770-8506, Japan

Abstract

Sudachiin A was isolated from the green peels of Citrus sudachi Hort. ex SHIRAI. This structure was deduced to be sudachitin 4’-β-D-glucoside by spectra and degradation, and confirmed by synthesis.

■ Preparation of Benzoxazoles from N-Alkylidene-2-hydroxyanilines and Silver Oxide

Masaaki Yoshifujii, Rihei Nagase, Takayuki Kawashima, and Naoki Inamoto*

*Department of Chemistry, School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

Oxidation of N-alkylidene-2-hydroxyanilines with silver oxide gave 2-alkyl- or 2-arylbenzoxazoles in good yields under mild reaction conditions.

■ Synthesis (±)-Mesembrine

Osamu Hoshino, Shohei Sawaki, Naomi Shimamura, Akira Onodera, and Bunsuke Umezawa*

*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

The base-catalyzed reaction of 2-(3’,4’-methylenedioxyphenyl)cyclohexanone (1a) and 5,5-ethylenedioxy-2-(3’,4’-dimethoxyphenyl)cyclohexanone (2a) with allyl bromide in the presence of 18-crown-6 afforded the 2-allyl-2-arylcyclohexanones (1b and 2b) in good yields, which was applied to the synthesis of (±)-mesembrine (3).

■ The Chemical Transformation of Reserpine to Deserpidine

Shin-ichiro Sakai* and Masaki Ogawa

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

Abstract

The partial synthesis of deserpidine 10b was achieved by the chemical transformation from reserpine 1. As a consequence of this investigation, a simple procedure for the preparation of deserpidine derivative having substituent group on the indole part has been discovered.

■ Preparation and Stereochemistry of Some Indole Alkaloid N-Oxides

Norio Aimi,* Etsuji Yamanaka, Masaki Ogawa, Teruo Kohmoto, Kin’ichi Mogi and Sin-ichiro Sakai

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

Abstract

Two N-oxides were obtained from yohimbine (1) on m-chloroperbenzoic acid oxidation. The major isomer (3) was shown to possess the stable trans-quinolizidine ring system through a chemical correla- tion with pseudoyohimbine N-oxide (5). A similar result was obtained for N-oxidation of dihydrocorynantheine (10). A possible reaction mechanism is proposed for the conversion of 3 to 3-hydroxy-yohimhine N-oxide (7).

■ Studies in the (+)-Morphinan Series VI. Dimers of Natural (—)- and Unnatural (+)-Sinomenine

Jun-ichi Minamikawa, Ikuo Iijima and Arnold Brossi*

*National Institute of Health, 9000 Rockville Pike, Bethesda, MD 20892-0815, U.S.A.

Abstract

Thermal equilibration of either (+)-disinomenine or (+)-ψ-disinomenine, obtained by chemical oxidation of natural (-)-sinommine, affords a 1:l mixture of the two readily separable dimers. Synthesis of the (-)-enantiomers of the two dimers was accomplished from unnatural (+)-sinomenine. Physical data collected with both enantiomeric pairs show that they are chemically and optically pure. These crystalline dimers contain tightly bound solvents of crystallization and are not suited for X-ray analysis.

■ Amorphaquinone, a New Isoflavan-quinone from Amorpha fruticosa L

Hisao Sibata and Sumio Simizu*

*Department of Chemistry, Faculty of Agriculture, Shinshu University, 8304 Minamiminowa-mura, Kamiina-gun, Nagano 399-4598, Japan

Abstract

From the root of Amorpha fruticosa L. (Leguminosae), a novel isoflavanquinone, amorphaquinone, was isolated whose structure was shown to be I on the basis of spectral data.

■ Facile Syntheses of Perillene and Dendrolasin

Shigeo Katsumura, Akio Ohsuka* and the late Munio Kotake

*Department of Chemistry, Faculty of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan

Abstract

A synthesis of perillene (Ia) was accomplished using the regioselective oxidation of the dienolate anion generated from methyl geraniate (IIa). Dendrolasin (Ib) was also synthesized from methyl farnesoate (IIb).

■ Reduction of Some Substituted 1,2,4-Triazines with Sodium Borohydride

Tadashi Sasaki,* Katsumaro Minamoto, and Katsuhiko Harada

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

Abstract

The structures of dihydro-1,2,4-triazines (2a-b) derived from 3-methoxy- (1a) and 3-methylthio-5,6-diphenyl-l,2,4-triazine (1b) were determined on the hasis of the ¹³C NMR spectra of the cyclo-adducts of the mono-methylated derivatives (3a-b) of 2a-b.

■ Synthetic Studies on β-Lactam Antibiotics 9. Trans-formations of Penicillin to 3’-Substituted Cephalosporins

Shoichiro Uyeo,* Tsutomu Aoki, Hikaru Itani, Teruji Tsuji and Wataru Nagata

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

Abstract

An important antibiotic cephalothin 4b was prepared from 2β-acetoxymethyl penicillin α-sulfoxide 1a which was derived from penicillin.

■ A General Method for the Preparation of 2-Substituted and 2,3-Disubstituted Furans. A New Synthesis of Sesquirose Furan

Hiroshi Kotake,* Katsuhiko Inomata, Hideki Kinoshita, Shin-ichi Aoyama, and Yasuko Sakamoto

*Department of Chemistry, Faculty of Siencce, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

Various 2-substituted and 2,3-disubstituted furans were prepared starting from 3-tosylpropanal ethylene acetal in two and three steps, respectively. Sesquirose furan was readily synthesized by the present method.

■ Synthesis of Optically Active 2-Ethyl-1,6-dioxaspiro[4.4]nonane(Chalcogran), the Principal Aggrega-tion Pheromone of Pityogenes Chalcographus (L.)

Kenji Mori,* Mitsuru Sasaki, Shigeharu Tamada, Toshio Suguro, and Satoru Masuda

*Department of Agricultural Chemistry, Faculty of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

Abstract

(2R,5RS)- and (2S, 5RS)-ethyl-1,6-dioxaspiro[4.4]nonanes (chalcograns) were synthesized in a simple manner by applying the recent technique of dianion chemistry.

■ Euponin: A New Epoxy Sesquiterpene Lactone Inhibiting Insect Development from Eupatorium japonicum

Shuhei Nakajima and Kazuyoshi Kawazu*

*Department of Chemistry, Depatment of Agricultural, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

Euponin, a new naturally occurring guaianolide inhibiting insect development, was isolated from the leaves of Eupatorium japonicum Thunb. (Compositae). Its structure was elucidated on the basis of chemical transformations and full spectral analysis.

■ New Congeners of Cytotoxic Nor-diterpenoid Dilactones in Podocarpus nagi : C₁₉ Lactones of an α-Pyrone Type and a 7:8,9:11-Dienolide Type

Yuji Hayashi,* Takeshi Matsumoto, and Takeo Sakan

*Faculty of Pharmaceutical Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan

Abstract

Two new members of the cytotoxic nor-diterpenoid dilactones were obtained from root bark of Podocarpus nagi and the structures were established by the correlation with the known lactones.

■ Synthesis of β-Hydroxy-α-amino Acids by Substitution Reactions of Thiazoline and Imidazoline Compounds

Tetsuo Shiba,* Kozo Sawada, and Yoshihiro Hirotsu

*Department of Chemistry, Faculty of Science, Osaka University, Toyonaka, Osaka 560-8531, Japan

Abstract

β-Hydroxy-α-amino acids were newly synthesized by the aldol condensation of 2-benzyloxycarbonylaminomethyl-2-thiazoline (II) or -2-imidazoline (VI) with aldehydes followed by acid hydrolysis.

■ Identification of cis-Zeatin-D-riboside from the Top of Tobacco Plant

Takeshi Hashizume,* Kazumasa Kimura, and Tamiji Sugiyama

*Department of Agricultural Chemistry, Faculty of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

Abstract

One of the cytokinin-active ribonucleosides, cis-zeatin-D-riboside has been purified and identified from the top of tobacco plant (Nicotiana tabacum L. cv. Shiroenshu) by means of gas chromatography-mass spectrometry of the purified extract. The level of the endogenous cytokinin in the top of tobacco plant was estimated to be the order of 10 ug/kg. Furthermore, relatively simple techniques employed in this study are also discussed.

■ The Stereospecificity of Diazomethane Cycloadditions

Werner Bihlmaier, Jochen Geittner, Rolf Huisgen,* and Hans-Ulrich Reissig

*Institut für Organische Chemie der Universitat, Karlstraße 23, D - 8000 München 2, Germany

Abstract

The 1,3-dipolor cycloadditions of diazomethane to methyl angelate and methyl tiglate proceed with >99.94 % and >99.997 % retention of dipolarophile configuration. The unconsumed dipolorophiles show < 0.008 and <0.0006 % cis, trans isomerizotion. The mechanistic implications are discussed.

■ Cycloaddition Rates of Diazomethane and Diphenyldiazomethane

Lubor Fisera, Jochen Geittner, Rolf Huisgen,* and Hans-Ulrich Reissig

*Institut für Organische Chemie der Universitat, Karlstraße 23, D - 8000 München 2, Germany

Abstract

Reactivity sequences of dipolarophiles are 1,3-dipole specific. Electron-attracting substituents increase the rate constants of alkenes and alkynes towards diazomethane and diphenyldiazomethane in DMF, whereas electron-releasing substituents decelerate; this is in accordance with a predominant HO(diazoalkane) - LU(dipolarophile) control. The cycloadditions of diazomethane are generally faster and more selective than those of diphenyldiazomethane. Similarly substituted ethylenes and acetylenes do not differ much in their dipolarophilic activity.

■ Biogenetic Type Synthesis of Blepharismone, a Conjugation Inducing Gamone in Ciliate Bleparisma

Takashi Tokoroyama,* Yoshinori Kawasaki, Miwako Nakatani and Kozo Shibata

*Faculty of Pharmaceutical Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan

Abstract

Blepharismone 1 was synthesized by oxidation of benzyl 5-benzyloxyindolyllactate 5 followed by deprotection, which was prepared by the reaction of 5-benzyloxyindolylmagnesium iodide 9 with benzyl glycidate 7.

■ Synthesis of 2-(1-Methyl-3-indolyl)-3-alkyl- or aryl-1,4-dioxenes

Hideshi Nakamura and Toshio Goto*

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

Abstract

The title dioxenes were synthesized by short steps from indole.

■ Synthesis of 2-Acylmethylpyrimidines from 2-Chloro-4,6-dimethylpyrimidine

Setsuko Niitsuma, Takao Sakamoto, and Hiroshi Yamanaka*

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

Abstract

The substitution of 2-chloro-4,6-dimethylpyrimidine with dimethylsulfoxonium methylide gave rise to dimethylsulfoxonium 4,6-dimethyl-2-pyrimidinylmethylide. The pyrimidinyl-sulfur ylide was acylated with acetic anhydride, benzoyl chloride, and ethoxycarbonyl chloride to afford the respective monoacyl derivatives, which were desulfurized to 2-acetonyl-, 2-phenacyl-, and 2-ethoxycarbonylmethyl-4,6-dimethylpyrimidines in good yields.

■ The Conversion of Furanoeremophilanes to Epieremophilenolides

Keizo Naya,* Takashi Matsuura, Masao Makiyama, and Minoru Tsumura

*School of Science, Kwansei Gakuin University, Gakuen, Sanda-shi 669-1337, Japan

Abstract

Various nonnatural eremophilane-type lactones (epieremophilenolides) were synthesized stereoselectively from furanofukinol (VI) by a photosensitized oxygenation procedure, and also by lactone cleavage and reformation. Their physical properties showed excellent agreement with those expected from a classification procedure proposed by us in earlier papers.

■ Neighboring Group Participation in Peptide Synthesis by the Use of Arylsulfonates of N-Hydroxyazoles and Related Compounds — Tautomeric Effect

Kusuo Horiki* and (in part) Atsuko Murakami

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

Abstract

The present paper deals with some attempt of the mechanistic elucidation an peptide bond formation using several arylsulfonates of N-hydroxy compounds and describes the important role of neighboring group involved in the N-hydroxy compounds in peptide synthesis.