HETEROCYCLES

■ Biographical Data

Yuichi Kanaoka*

*Toyama College, Toyama, Toyama-city Gankaiji, Japan

■ YUICHI KANAOKA: A Pioneer in Chemical Biology

John W. Daly

*Chief, Pharmacodynamics, Laboratory of Bioorganic Chemistry, NIDDK, NIH

■ Understanding Life Process by Chemistry
- A Tribute to the Contributions of Professor Yuichi Kanaoka in Heterocyclic Chemistry and Bioorganic Chemistry -

Minoru Machida, Kazutaka Tanizawa, Eisuke Sato, Hitoshi Nakayama, and Yasumaru Hatanaka

*,

■ Congratulatory Message

Dr. and Mrs. Bernhard Witkop

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

■ Publications

Yuichi Kanaoka*

*Toyama College, Toyama, Toyama-city Gankaiji, Japan

■ The Aggregation of 8-Formylamino-2-Carboxamidochromenone Heterocycles in Solution

Luis Simón, Jose Vicente Hernández, Ana Isabel Oliva, Francisco Muñoz Muñiz, Cruz Caballero, Francisca Sanz, and Joaquín Rodríguez Morán*

*Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos, 37008 Salamanca, Spain

Abstract

Formyl-substituted chromenone receptors have been prepared and their self-association process were studied in chloroform solutions. The structure of the aggregates depends on the configuration of the formyl group. The Z/E ratio dependence with the molar concentration and X-Ray crystallographic data is used to discuss the structure of the associates.

■ High-pressure Cycloaddition Reaction of 1,3-Diphenylisobenzofuran with 6,6-Diphenylfulvene

Kanji Kubo,* Katsuji Hirowatari, Nobuo Kato, and Akira Mori*

*Instituete of Advanced Material Study, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

Abstract

High-pressure cycloaddition reaction of 1,3-diphenylisobenzofuran with 6,6-diphenylfulvene gave exo- and endo-[4+2]π cycloadducts in 29 and 20% yields, respectively. The structures of exo- and endo-[4+2]π cycloadducts were elucidated by X-Ray crystallographic analysis, the latter of which included a benzene molecule.

■ Asymmetric Intramolecular Aza-Michael Reaction Using Enviromentally Friendly Organocatalysis

Kiyosei Takasu,* Soumen Maiti, and Masataka Ihara*

*Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University

Abstract

This communication describes enantioselective intramolecular aza-Michael reaction to prepare 1,2,3,4-tetrahydroisoquinolines by using organocatalysts. The organocatalytic reaction offers new green chemical process in heterocyclic chemistry. Additional noting, both enantiomers of the product were easily synthesized by using two types of organocatalysts prepared from the same amino acid.

■ Bowl-shaped [Tris(2,6-diphenylbenzyl)-siloxy]dimethylaluminum Catalyst for Effecting Tishchenko Reaction

Seiji Shirakawa, Jun Takai, Kouji Sasaki, Tomoya Miura, and Keiji Maruoka*

*Department of Chemistry, Gradauate Schol of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan

Abstract

High-speed Tishchenko reaction of various aldehydes can be realized by using a bowl-shaped [tris(2,6-diphenylbenzyl)siloxy]dimethylaluminum catalyst, which is readily prepared by treatment of tris(2,6-diphenylbenzyl)silanol with trimethylaluminum.

■ First Synthesis and Cycloaddition Reactions of 1-Azaazulene N-Ylide

Hiroyuki Fujii,* Kaoru Iwafuji, Yoshiyuki Sawae, Noritaka Abe, and Akikazu Kakehi*

*Department of Chemistry, Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan

Abstract

2-Substituted 1-azaazulene N-ylides were generated by the treatment of appropriate 1-trimethylsilylmethyl-1-azaazulenium triflates with CsF; the triflate salts were prepared from 1-azaazulenes and trimethylsilylmethyl triflate. The 1,3-dipolar cycloadditions of 2-chloro-1-azaazulene N-ylide, prepared in situ, with acetylenic esters gave 2a-azabenz[cd]azulene derivatives and 3a-azacyclopent[a]naphthalene derivatives. These structures were determined by X-Ray crystal structure analysis. A similar reaction of 2-piperidino-1-azaazulene N-ylide gave 3a-azacyclopent[a]azulene derivative as major product.

■ Intermolecular Photoreaction of Benzenecarbothioamide with β-Ionone

Kazuaki Oda,* Rikiji Nakagami, Michiko Haneda, Naozumi Nishizono, and Minoru Machida*

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

Abstract

Irradiation of benzenecarbothioamide with β-ionone in benzene gives 1,5,6,7,8,8a-hexahydroquinoline derivative in moderate yield.

■ The Sonogashira Reaction in Water via an Amphiphilic Resin-supported Palladium-Phosphine Complex under Copper-free Conditions

Yasuhiro Uozumi* and Yukinari Kobayashi

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

Abstract

The Sonogashira reaction of aryl halides with terminal alkynes was catalyzed by an amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin-supported palladium-phosphine complex in water to give the corresponding aryl-substituted alkynes in high yields under copper-free conditions. Reaction of o-iodophenol with terminal alkynes under Sonogashira conditions gave benzofuran derivatives in one step.

■ Synthesis of the N-Terminus of Glycopeptide Unit for Aeruginosin 205-A

Naoki Toyooka,* Akiko Nakazawa, Toshiyuki, Himiyama, and Hideo Nemoto*

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

Abstract

The N-terminus moiety of glycopeptide unit for aeruginosin 205-A has been synthesized.

■ Studies towards the Biomimetic Synthesis of Ginsenoyne L; Efficient Synthesis of 2’-epi-Ginsenoyne L

Jack E. Baldwin,* Robert M. Adlington, Peter J. Wilkinson, Rodolfo Marquez, and Mauro F. A. Adamo

*Dyson Perrins Laboratory, Oxford University, South Parks Road, Oxford OX1 3QY, U.K.

Abstract

The biomimetic synthesis of 2’-epi-gynsenyone L has been accomplished in 7 steps and in good yield through the novel use of bis-acetylenic enones as hetero Diels-Alder dienes for the mild and easy generation of dihydropyrans.

■ A Novel Route to 1,8-Dihydroxynaphthalene-derived Natural Products. Synthesis of (±)-CJ-12,372

Masayuki Inoue, Kazuyuki Nabatame, and Masahiro Hirama*

*Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan

Abstract

1,8-Dihydroxynaphthalene-derived natural products show a wide variety of biological activities, and thus have the attracted interest of both the chemical and biological communities. We report a novel and efficient approach to these natural products and its application to the total synthesis of (±)-CJ-12,372, a representative example of this class of compounds.

■ Acid-Catalyzed Intramolecular Addition of a Hydroxy Group to Vinylgermanes

Katsukiyo Miura, Tatsuyuki Takahashi, and Akira Hosomi*

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

Abstract

Vinylgermanes (1), bearing a hydroxy group, were efficiently cyclized to 2-(germylmethyl)tetrahydrofurans (2) in the presence of an acid catalyst. The intra-molecular addition of the hydroxy group proceeded in a stereospecific syn mode. The acid-catalyzed cyclization of α-alkyl-substituted vinylgermanes (8) gave 1,2-germyl-migration products (9).

■ Regiocontrol in Pd-Catalyzed Allylic Substitution with P,N-Ligand

Kazuhiro Kondo,* Kumiko Kazuta, Atsushi Saitoh, and Yasuoki Murakami*

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

Abstract

A racemic ligand, (±)-N-[2-(diphenylphosphino)naphthyl]-2-(pyrrolidinylmethyl)piperidine, has been found to exhibit better regioselectivity than the racemic Pfaltz ligand, BINAP and dppp in the palladium-catalyzed regioselective allylic substitution with the use of (E)-1-phenyl-4-alkoxy-2-butenyl acetate as the substrate.

■ Stereoselective Syntheses of 2,5-Disubstituted Hydroxyfuran Derivatives as Synthon of Polyether Antibiotics

Shinji Nagumo,* Yusuke Ishii, Shinya Kanno, and Norio Kawahara*

*Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, Otaru 047-02, Japan

Abstract

Stereoselective syntheses of optically active 2,5-dialkyltetrahydrofurans (8), (11) and (12), which correspond to a central moiety of pamamycin 607, have been achieved on the basis of lactone-ring transformation via a phenonium ion, intramolecular Friedel-Crafts reaction, oxidative decomposition of an aromatic ring and differentiation of two ester groups by a chemical or chemo-enzymatic method.

■ Toward the Assignment of Liposidomycin Stereochemistry: Synthesis of 1,4-Diazepan-3-One Analogues by Reductive Amination Approach

Noriyuki Nakajima,* Takahiro Isobe, Shiro Irisa, and Makoto Ubukata*

*Biotechnology Research Center, Toyama Parefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398

Abstract

Toward the assignment of liposidomycin stereochemistry, a stereocontrolled synthesis of the liposidomycin diazepanone ring system and two precursors, has been achieved. The NMR coupling constants of a 5-phenyl model compound closely related to the liposidomycin diazepanone degradation product.

■ A Simple One-Pot Synthesis of Benzoxazine-2,4-diones and Benzothiazine-2,4-diones

Xiaoxiang Zhu, Qian-sheng Yu, Nigel H. Greig,* Judith L. Flippen-Anderson, and Arnold Brossi

*Drug Design & Development Section, Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging Intramural Program, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825, U.S.A.

Abstract

A simple and efficient procedure has been developed for a one-pot synthesis of substituted benzoxazine-2,4-diones and benzothiazine-2,4-diones directly from salicylic acid (or thiosalicylic acid) and amines.

■ A Direct Conversion of 5,6,7,8-Tetrahydro-2H-1-benzopyran-2,5-diones into Substituted 1-Amino-5,6,7,8-tetrahydroquinoline-2,5-diones

Polonca Trebse, Slovenko Polanc, and Marijan Kočevar

*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, SLO-1000 Ljubljana, Slovenia

Abstract

A highly selective transformation of 5,6,7,8-tetrahydro-2H-1-benzopyran-2,5-diones (1a-c) with hydrazides, arylhydrazines and heterocyclic hydrazines as nitrogen-containing nucleophiles (2) into the corresponding 1-amino-5,6,7,8-tetrahydroquinoline-2,5-diones (5-17) was investi-gated. The reac-tion was carried out in the mixture of ethanol, water and triethylamine, and the corresponding quinoline-2,5-diones were obtained in 52-89% yields. The com-pounds (3) and (4) were proposed to be intermediates in this transformation.

■ The First Example of an Amide-Carbonyl Stabilized Oxiranyl Anion: Generation from Epoxysilane, Its Properties, and Trapping with Electrophiles

Tsuyoshi Satoh,* Takayuki Shimura, and Ken Sakai

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

Abstract

An epoxysilane having an amide group at the α-carbon was synthesized from phenylacetylene. An amide-carbonyl stabilized oxiranyl-ammonium was generated from the epoxysilane in THF with tetrabutylammonium fluoride (TBAF). The generated oxiranyl anion was found to have enough nucleophilicity with aldehydes to give moderate to good yields of the adducts. In some reactions, the oxiranylammonium was found to be configurationally unstable to give the epimers.

■ Synthesis of Spiro-fused Nitrogen Heterocyclic Compounds via N-Methoxy-N-acylnitrenium Ions Using Phenyliodine(III) Bis(trifluoroacetate) in Trifluoroethanol

Etsuko Miyazawa, Takeshi Sakamoto, and Yasuo Kikugawa*

*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

Spirodienones and spirodienes bearing the nitrogen atom bound to the spiro carbon have been synthesized from N-methoxy-(4-methoxyphenyl)amides and N-methoxyphenylamides, respectively, by the intramolecular ipso attack of a nitrenium ion generated with phenyliodine(III) bis(trifluoroacetate) in trifluoroethanol.

■ 3-Cyano-2-(N-cyanoimino)thiazolidine (3-cyano-NCT): An Efficient Electrophilic Cyanating Agent for Activated Methylene Compounds

Naoyoshi Maezaki, Akemi Furusawa, Shuji Uchida, and Tetsuaki Tanaka*

*Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan

Abstract

We found that 3-cyano-2-(N-cyanoimino)thiazolidine (3-cyano-NCT) is a novel electrophilic cyanating agent. Various activated methylene compounds were cyanated in moderate to good yields.

■ A Formal Total Synthesis of Securinine via an Intramolecular [4+2]Cycloaddition Reaction

Toshio Honda,* Hidenori Namiki, Mika Kudoh, Hiromasa Nagase, and Hirotake Mizutani

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

An intramolecular Diels-Alder reaction of the enol ester derived from 2-acetylpyridine and sorbic anhydride gave the cycloaddition product, stereoselectively, which was further converted into the key intermediate for the synthesis of securinine.

■ Hexafluoroacetone as Protection and Activation Reagent in Amino Acid and Peptide Chemistry Regiospecific α-Functionalization of Aspartic Acid

Klaus Burger,* Torsten Lange, and Martin Rudolph

*Department of Organic Chemistry, University of Leipzig, Johannisallee 29, D-04103 Leipzig, Germany

Abstract

A highly efficient method for regiospecific α-functionalization of aspartic acid is described. Key step is the synthesis of a N-protected and regioselectively α-carboxy-activated heterocyclic intermediate from aspartic acid and hexafluoroacetone. The new strategy offers i.a. a two step access to the sweetener Aspartame^® and to libraries of aspartame analogues.

■ Reaction of 8-Amino-3-phenyl-1-azaazulene with Chloro-, Phenyl-, and Diphenylketene

Noritaka Abe,* Akifumi Otani, Taizo Nagai, and Hiroyuki Fujii

*Department of Chemistry, Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan

Abstract

Chloroketene reacted with 8-amino-3-phenyl-1-azaazulene (1) to give 2,2a-dihydro-2a-azacyclopent[cd]azulen-2-one derivative (2a), as a cycloadduct, along with ethyl (3-phenyl-1-azaazulen-8-yl)aminocarboxylate (3a) and 8-chloroacetylamino-3-phenyl-1-azaazulene (4a). Compound (2a) was formed by the reaction of 4a with chloroketene. Formation mechanism of 2a, 3a and 4 was discussed. Phenylketene and diphenylketene reacted with 1 to give 8-phenylacetylamino- (4b) and 8-diphenylacetylamino-3-phenyl-1-azaazulene (6) as major products,respectively. Further treatment of 6 with diphenylketene gave 2-diphenylmethylene-4-phenyl-2,2a-dihydro-1,2a-diazacyclopent[cd]azulene (7).

■ Synthesis of Oligonucleotides with 6-Formyl-2’-O-Methyluridine and Thermal Stability of their Duplexes

Atsushi Kittaka,* Tetsuya Kuze, Akinori Sarai, Hiroaki Takayama, Hiromichi Tanaka, Tadashi Miyasaka, Jun-ichiro Inoue, and Shunsuke Ishii*

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

Abstract

Single 6-formyl-2’-O-methyluridine or 2’-O-methyluridine was introduced into oligonucleotides (9-23 mers), which have simple base-sequences, as a substituent for thymidine to compare the ability of duplex formation and the thermal stability of the resulting duplexes.

■ Convenient Synthesis of a Simple Coumarin from Salicylaldehyde and Wittig Reagent. IV^1a-c: Improved Synthetic Method of Substituted Coumarins

Yasuo Takeuchi,* Norihiro Ueda, Koji Uesugi, Hitoshi Abe, Hiromi Nishioka, and Takashi Harayama*

*Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

The reaction of salicylaldehydes (2) with Horner-Wadsworth-Emmons (HWE) or Ando-HWE reagents was attempted to afford intramolecular phosphonate derivatives (6). A new synthetic method for coumarins (1) was achieved by using protected 2.

■ The Preparation and Reactions of 2-Acyl-3-Phenylisomenthopyrazole

Choji Kashima,* Yohei Miwa, Takeshi Yokawa, and Saori Shibata

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

Abstract

3-Phenylisomenthopyrazole (4) was useful as a chiral auxiliary, though the diastereomeric selectivity was lower than those of 3-phenyl-l-menthopyrazole (1a). In α-acylation and the Diels-Alder cycloaddition, the absolute configuration of the predominant products was different from that of the products using 1a.