HETEROCYCLES

■ Contents

■ Preface

Gilbert Stork

*,

■ Preface

Edward C. Taylor

*A. Barton Hepburn Professor of Organic Chemistry Emeritus, Princeton University, Princeton, New Jersey 08544

■ Preface of the Special Issue "30 Years Heterocycles"

Arnold Brossi

*School of Pharmacy, University of North Carolina at Chapel Hill
and
Scientist Emeritus, National Institutes of Health, Bethesda

■ Preface

Teruaki Mukaiyama

*,

■ Editor‘s Note

Keiichiro Fukumoto

*Editor in Chief

■ 2-Amino-5-hydroxyhexanoic Acid and Its Succinyl Derivatives as Their Lactone Forms from Kobutorisou, an Antagonizing Plant to Nematode

Tadahiro Kato,* Kenji Fujisawa, and Yuuki Shimizu

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

Abstract

Minute amounts of 2-acetylamino-5-hydroxyhexanoic acid (1) and its succinyl derivatives (2a) and (2b) as their lactones, and 2,3-diacetoxy-2-methyl- butanolide (3) were isolated from kobutorisou, an antagonizing plant to nematode, after Ac₂O-treatment of the anti-nematode fraction of extracts of kobutorisou.

■ A Total Synthesis of a New Type of Furo[3,2-h]isoquinoline Alkaloid, TMC-120B

Teppei Kumemura, Tominari Choshi, Aki Hirata, Mitsuko Sera, Yohhei Takahashi, Junko Nobuhiro, and Satoshi Hibino*

*Graduate School of Pharmacy and Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan

Abstract

A total synthesis of a new furo[3,2-h]isoquinoline alkaloid, TMC-120B (2) has been completed in sixteen steps. The key step is the synthesis of 7,8-disubstituted isoquinoline (17) based on the thermal electrocyclic reaction of 1-azahexatriene system involving the benzene 1,2-bond.

■ A Novel Ring Transformation of Nitropyrimidinone Leading to Polyfunctionalized Pyridones

Nagatoshi Nishiwaki,* Hiromi Morimura, Kazuo Matsushima, Mina Tamura, and Masahiro Ariga*

*Department of Chemistry, Osaka Kyoiku University, Asahigaoka, Kashiwara, Osaka 582-8582, Japan

Abstract

Polyfunctionalized 2-pyridones are readily prepared by the ring transformation using 3-methyl-5-nitropyrimidin-4(3H)-one with active methylene compounds in the presence of piperidine.

■ Toward a Total Synthesis of Keramamide B

Takayuki Shioiri* and (the late) Robert John Hughes

*Graduate School of Environmental and Human Sciences, Meijo University, Shiogamaguchi, Tempaku, Nagoya 468-8502, Japan

Abstract

Important building blocks, the 2-bromo-5-hydroxytryptophan-oxazole unit, the α-keto-β-amino acid unit, and the side chain units, for the preparation of keramamide B were efficiently synthesized.

■ Stilbazolium Boronic Acid/Borate - A New Stilbazolium Betaine Dye: An Optical Molecular Sensor for Monosaccharides

Kiyoshi Sato,* Akiko Sone, Sadao Arai, and Takamichi Yamagishi

*Department of Applied Chemistry, Graduate School of Engineering, Tokyo Metropolitan University, 1-1 Minami-ohsawa, Hachioji, Tokyo 192-0397, Japan

Abstract

The Knoevenagel condensation of 1,4-dimethylpyridinium and 1,4-dimethylquinolinium salts with 4-formylbenzeneboronic acid gave new stilbazolium dyes (2) and (3), respectively. The UV-VIS absorption behavior of the boronic acid-substituted stilbazolium dyes were studied in acetonitrile-aqueous buffered solutions (1:25 v/v), in the absence and in the presence of various sugars as guest species. The dyes form complexes with monosaccharides at neutral pH together with a bathochromic shift of the intramolecular charge transfer band.

■ Synthesis of Various Macrosphelides by Oxidative Derivatization of the Macrosphelide Core

Yuji Matsuya, Takanori Kawaguchi, and Hideo Nemoto*

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

Abstract

The macrosphelide core (4), simple 16-membered trilactone, was subjected to several oxidative conditions to produce various natural macrosphelide analogues, including macrosphelides A and C. This approach provided a new access to diverse macrosphelides for a study on their structure-activity relationships.

■ Useful Synthesis of the Main Central 2,3,6-Trisubstituted Pyridine Skeleton of Various Thiostrepton-Type Macrocyclic Antibiotics

Chung-gi Shin,* Hirofumi Saito, and Yasuchika Yonezawa

*Laboratory of Organic Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

A useful synthetic method for the main central 2-(2-oxazol-4-yl)-3- (4-thiazol-2-yl)-6-carboxypyridine skeleton [Fragment A] constructing various thiostrepton-type macrocyclic antibiotics is described, in which the precursor of Fragment A was derived from the authentic ethyl 2-(6-dimethoxymethyl-2-tri- fluoromethanesulfonyloxy-3-pyridyl)thiazole-4-carboxylate in 14 steps. Finally, the fragment condensation of Fragment A with the already prepared carboxy component dipeptide [Fragment B] proceeded first to give the precursor of Fragment A-B.

■ Effective Induction of β-Selectivity Using α- or β-Mannosyl 6-Nitro-2-benzothiazoate in Mannosylation

Takashi Hashihayata and Teruaki Mukaiyama*

*Center for Basic Research, The Kitasato Institute (TCI), 6-15-5, Toshima, Kita-ku, Tokyo 114-0003, Japan

Abstract

Highly β-selective mannosylations of glycosyl acceptors with an α-mannosyl 6-nitro-2-benzothiazoate donor (1α) were carried out smoothly in the presence of a catalytic amount of tetrakis(pentafluorophenyl)boric acid [HB(C₆F₅)₄] to afford the corresponding disaccharides in good to high yields: it was proved that high β-selectivity was entirely dependent on the characteristic properties of a donor (1α) and a catalyst, HB(C₆F₅)₄. Interestingly, it was observed that in situ anomerization from 1β to 1α took place rapidly when β-mannosyl donor (1β) was treated with a catalytic amount of HB(C₆F₅)₄ in CH₂Cl₂.

■ Preparation and Derivatization of the Core Compound of Macrosphelide E-G Series

Yuji Matsuya, Kentaro Ishihara, Nobutaka Funamori, Takanori Kawaguchi, and Hideo Nemoto*

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

Abstract

The macrosphelide core (2) possessing a skeleton of macrosphelide E-G series was newly prepared, and its oxidative derivatization was investigated. The compound (2) was found to be less reactive to oxidations compared to the epimeric core (1), and it was suggested that there is a considerable difference among their geometry-optimized conformations, which affected the reactivity.

■ Novel Synthesis of Azocine, Azepine, Oxocine, and Oxepine Derivatives by Palladium-catalyzed Medium-Ring Formation from Bromoallenes

Hiroaki Ohno,* Hisao Hamaguchi, Miyo Ohata, Shohei Kosaka, and Tetsuaki Tanaka*

*Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan

Abstract

Novel and efficient synthesis of medium-sized heterocycles such as azepine, oxepine, and benzo[d]azocine derivatives is described. Treatment of bromoallenes having a nucleophilic moiety with sodium alkoxide and a palladium(0) catalyst in the presence of an alcohol leads to regioselective formation of medium-sized rings at the central position of the allenic carbon.

■ Biomimetic Synthesis of 4,4’-Dimethoxycarbonyl-2,2’-bioxazole

Wieslaw Z. Antkowiak* and Izabella Kopysc-Lapinska

*Faculty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-790 Poznán, Poland

Abstract

Serine and oxalic acid were used as building blocks of natural origin to prepare 2,2’-bioxazole bearing methoxycarbonyl groups at 4,4’ positions.

■ Electrochemical Synthesis of Spiroisoxazole Derivatives and Its Application to Natural Products

Takahisa Ogamino, Yuichi Ishikawa, and Shigeru Nishiyama*

*Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan

Abstract

Efficient synthesis of the trans-spiroisoxazole (1) and its unnatural cis-isomer (2) was accomplished by employing anodic oxidation of 4, followed by Zn(BH₄)₂ reduction. This method was applied to an assembly of the carbon framework of zamamistatin (12).

■ Chemistry of Antitumor Isoquinolinequinone Alkaloids: Unexpected Oxidative Degradation of Saframycin S to Generate Simple Isoquinoline Alkaloids, Mimosamycin and Mimocin

Naoki Saito,* Yu-ichi Koizumi, Chieko Tanaka, Khanit Suwanborirux, Surattana Amnuoypol, and Akinori Kubo*

*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

Saframycin S, prepared by treating saframycin A with silver nitrate in aqueous acetonitrile, was transformed into simple isoquinolinequinones, mimosamycin and mimocin, by treatment with a catalytic amount of trifluoroacetic acid (TFA) in chloroform. The proposed mechanism for this oxidative degradation is presented.

■ Enantioselective Synthesis of the G-Ring of Brevetoxin A

Michael T. Crimmins* and Pamela A. Cleary

*Department of Chemistry, CB 3290, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, U.S.A.

Abstract

An enantioselective synthesis of the eight-membered G-ring of brevetoxin A is described. The synthesis exploits a ring-closing metathesis reaction to construct the eight-membered ether ring. The stereochemistry of the α and α’ centers of the ether linkage were established through a Sharpless kinetic resolution and an asymmetric glycolate alkylation reaction.

■ Synthesis of 2-Substituted Benzimidazoles by Reaction of o-Phenylenediamine with Aldehydes in the Presence of Sc(OTf)₃

Kazuhiro Nagata, Takashi Itoh, Hiroyuki Ishikawa, and Akio Ohsawa*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

2-Substituted benzimidazoles were synthesised under mild conditions by reaction of o-phenylenediamine with aldehydes in the presence of Sc(OTf)₃ as a Lewis acid catalyst.

■ Montmorillonite Impregnated with Bismuth Nitrate: Microwave-assisted Facile Nitration of β-Lactams

Bimal K. Banik,* Susanta Samajdar, Indrani Banik, Sze Sze Ng, and Jennie Hann

*The University of Texas, M. D. Anderson Cancer Center, Department of Molecular Pathology, Box 89, 1515 Holcombe Boulevard, Houston, Texas 77030, U.S.A.

Abstract

A facile synthesis of nitro substituted β-lactams over montmorillonite impregnated with bismuth nitrate under microwave irradiation has been accomplished in excellent yield.

■ A New Bismuth Nitrate-induced Stereospecific Glycosylation of Alcohols

Bimal K. Banik,* Dorothy Adler, Phuong Nguyen, and Neeta Srivastava

*The University of Texas, M. D. Anderson Cancer Center, Department of Molecular Pathology, Box 89, 1515 Holcombe Boulevard, Houston, Texas 77030, U.S.A.

Abstract

Bismuth nitrate-catalyzed stereospecific glycosylation of alcohol with glycal has been developed.

■ Transformation of N-(5-Acetyl-6-methyl-2-oxo-2H-pyran-3-yl)benzamide with Hydrazines in the Presence of an Acidic Catalyst

Lidija Vranicar, Slovenko Polanc, and Marijan Kočevar*

*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, SI-1000 Ljubljana, Slovenia

Abstract

2H-Pyran-2-one derivative (1) was transformed with heterocyclic hydrazines and 2,4-dinitrophenylhydrazine, under the influence of various acidic catalysts, into N-[5-(1-hydrazonoethyl)-6-methyl-2-oxo-2H-pyran-3-yl]benzamides (3) as the main products, accompanied in some cases by the corresponding (E)-α,β-didehydro-α-amino acid derivatives (4).

■ Synthesis and Bridgehead Reactions of 9-Substituted 5,6,7,8,9,10-Hexahydro-5,9-Methanopyrimido[4,5-b]azocin-4(3H)-ones

Edward C. Taylor* and Beena Bhatia

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

Abstract

The condensation of a variety of 6-amino-4(3H)-pyrimidinones with 2-cyclohexen-1-one in water, and replacement of the bridgehead 9-hydroxy group in the resulting Michael/cyclization adducts with carbon nucleophiles, are described. These reactions have been exploited for the preparation of a novel bridged tricyclic analog of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).

■ Enantiocontrolled Total Synthesis of (+)-Heliannuol D via Palladium-mediated Heterocyclization

Hidetoshi Kishuku, Tomoyuki Yoshimura, Toshiyuki Kakehashi, Mitsuru Shindo, and Kozo Shishido*

*Institute for Medicinal Resources, University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan

Abstract

An enantiocontrolled total synthesis of (+)-heliannuol D has been accomplished using a palladium-catalyzed cyclization of the seven-membered oxygen containing heterocycle as the key reaction.

■ Stereoselective Construction of Four Consecutive Stereocenters Using [2,3]-Wittig Rearrangement Reaction

Masahiro Toyota,* Masako Hirota, Takanobu Asoh, and Masataka Ihara*

*Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

A diastereoselective construction of four consecutive stereocenters has been achieved using [2,3]-Wittig rearrangement reactions of oxazoline derivatives.

■ Synthesis of Indolo[1,2-b]indazole Derivatives

Yong-ming Zhu, Kimiyoshi Kaneko, Osamu Kato, Yoshimitsu Kiryu, Noriyuki Takatsu, Kazuhiko Shiono, and Hajime Katayama*

*School of Pharmacy, Niigata University of Pharmacy and Applied Life Science, 5-13-2 Kamishin'ei-cho, Niigata city, 590-2081, Japan

Abstract

New methods to synthesize indolo[1,2-b]indazole derivatives as an extension of available methods and thiol reduction of ketone to methylene peculiar to this skeleton were presented.

■ Nucleophilic Substitution Reaction at the 1-Position of 1-Hydroxytryptamine and -tryptophan Derivatives

Fumio Yamada, Aya Goto, Wu Peng, Toshikatsu Hayashi, Yoshitomo Saga, and Masanori Somei*

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

Abstract

A novel nucleophilic substitution reaction at the 1-position of indole nucleus was discovered by reacting 1-hydroxytryptamine and -tryptophan derivatives with indoles in 85% formic acid yielding 1-(indol-3-yl)indoles. Their structures were determined by X-Ray crystallographic analysis and chemical correlations. An SN2 mechanism on the indole nitrogen (1-position) is proposed.

■ Amine-induced Rearrangement of 4-Imino-4H-3,1-benzoxazines to 4-Quinazolinones via Amidine Carboxamides

Barry B. Snider* and Hongbo Zeng

*Department of Chemistry MS 015, Brandeis University, Waltham, MA 02454-9110, U.S.A.

Abstract

Iminobenzoxazines (2) react with pyrrolidine in EtOAc at reflux to give amidine carboxamides (11), which cyclize to quinazolinones (3) on heating in 99:1 MeCN/HOAc. However, both amidines (11d) and (13d) are formed if R¹ = Ar and R² = Me. Hindered amidine (11f), R¹ = Ph, R² = i-Pr, does not cyclize to give quinazolinone (3f).