HETEROCYCLES

■ Contents

■ Isolation and Identification of an Allelochemical Exuded from Germinating Pea (Pisum sativum) Seeds

Keiko Higashinakasu, Kosumi Yamada,* Hideyuki Shigemori, and Koji Hasegawa

*Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

Abstract

When pea seeds were cultured in a Petri dish together with cress seeds, the hypocotyl and root growth of cress was significantly inhibited, whereas the epicotyl growth of pea was promoted. These results suggest that the growth of each seeds is either inhibited or promoted with allelochemical(s) exuded from each seeds during seed germination. An allelochemical, which showed a growth-inhibiting activity against cress seeds, was isolated from the exudates of germinating pea seeds. It was identified as 6a-hydroxy-3-methoxy-8,9-methylenedioxy peterocarpan (pisatin) based on its ¹H NMR spectrum. The endogenous pisatin level (22 mg/L) in the exudates from germinating pea seeds seems to be a good agreement with the exogenous concentration (>3 mg/L) of pisatin required to inhibit the hypocotyl and root growth of cress. These results suggest that pisatin may play an important role in the allelopathy of pea seeds during germination.

■ Palladium(0)-catalyzed Amino-Heck Reaction of γ,δ-Unsaturated Ketone N,N,N-Trimethylhydrazonium Salts

Mitsuru Kitamura, Hideyuki Yanagisawa, Motoki Yamane, and Koichi Narasaka*

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

Abstract

Oxidative addition of N,N,N-trialkylhydrazonium salts takes place to a palladium(0) complex, resulting the formation of alkylideneaminopalladium(II) species. This N–N bond scission process is applied to the transformation of γ,δ-unsaturated ketone hydrazonium salts to pyrroles by amino-Heck reaction.

■ Base-induced Generation of Aryl(1,2,3-triazol-1-yl)carbenes from 1-[(N-Phenylsulfonyl)benzohydrazonoyl]-1,2,3-triazoles and Their Ring Enlargement to 3-Aryl-1,2,4-triazines

Yuumo Tanaka,* Shuji Oda, Suketaka Ito, and Akikazu Kakehi

*Department of Environmental Science and Technology, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan

Abstract

The Bamford-Stevens reactions of 1-[N-(phenylsulfonyl)benzohydrazonoyl]-1,2,3-triazoleÅ@derivatives, readily available from the 1,3-dipolar cycloadditions ofÅ@N-(phenylsulfonyl)benzohydrazonoyl azides with enamines, were examined and the transformation from aryl(1,2,3-triazol-1-yl)carbene intermediates to the corresponding 3-aryl-1,2,4-triazine derivatives was first observed.

■ The Sesquiterpenoids from Cynara scolymus

Xiaoli Li, Pingli Qian, Zeyuan Liu, Yu Zhao, Gang Xu, Deding Tao, Qinshi Zhao,* and Handong Sun

*State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Heilongtan, Kunming 650204, Yunnan, China

Abstract

Two new guaiane-type sesquiterpene lactones, cynarinins A (1) and B (2), together with seven known compounds, cynarascoloside C (3), cynaropicrin (4), aguerin B (5), grosheimin (6), dehydrocynaropicrin (7), aguerin A (8) and cynartriol (9), were isolated from aerial part of Cynara scolymus. The structures of new compounds were elucidated by means of 1D NMR, 2D NMR and HRMS spectral analysis. Cynaropicrin (4) and grosheimin (6) showed weak cytotoxicity against MCF-7 cancer cell line, and other compounds had no obvious activity against the same cell line.

■ Synthesis of the Amidite Reagent to Built Bipyridine Units into DNA Backbone

Toshihiro Ihara,* Yoshinori Shirasaka, Yoshinobu Sato, Yusuke Kitamura, Kenji Okada, Masato Tazaki, and Akinori Jyo

*Department of Applied Chemistry and Biochemistry, Faculty of Engineering, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan

Abstract

A new amidite reagent (9) containing 6,6’-bis(acylamino)-2,2’- bipyridine unit was synthesized in moderate yields by a dependable eight step procedure. The unit should work as a metal ion-directed conformational modulator when it is built into the backbone of synthetic DNAs.

■ The Structural Variation in the Incubation Products of (-)-Epigallocatechin Gallate in Neutral Solution Suggests Its Breakdown Pathways

Tsutomu Hatano,* Takayo Ohyabu, and Takashi Yoshida

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

Abstract

Three new compounds, in addition to previously reported compounds, were isolated from a product mixture obtained on incubating (-)-epigallocatechin gallate (EGCG) in neutral solution. The products were two monomeric (EGCG-MOx-M3 and EGCG-MOx-M4) and one dimeric (EGCG-MOx-D4) structure involving the flavan skeleton. Possible oxidation-reduction pathways producing drastic changes in the structure of EGCG were presented based on the structures of the breakdown products.

■ New Application of Triphosgene in a Convenient Synthesis of 3-Aryl-1,3-benzoxazine-2,4-diones from Anacardic Acids

Inês Sabioni Resck,* Maria Lucilia dos Santos, and Luiz Antonio Soares Romeiro

*Center of Biooorganic and Medicinal Chemistry, Catholic University of Brasilia, QS 07, Lote 01, Taguatinga-DF, 71966-700, Brazil

Abstract

In conjunction with a search program focused on utilization of cashew (Anacardium occidentale) nut shell liquid (CNSL) as starting material for the preparation of useful compounds, a convenient synthesis of novel series of 3-aryl-1,3-benzoxazine-2,4-diones was prepared from anacardic acids by using of the triphosgene.

■ The First Synthesis of (S)-(+)-Cacalol

Shin Tanikawa, Michiko Ono, and Hiroyuki Akita*

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

Abstract

The first synthesis of (S)-(+)-cacalol (1) was achieved by a combination of the BF₃·Et₂O–mediated reaction of (S)-4,5-epoxy-(2E)-pentenoate (7) with 3,4-dimethoxytoluene to give (S)-4-aryl-5-hydroxy-(2E)-pentenoate (5) and consecutive conversion of (S)-5 into (S)-1.

■ A Synthetic Route To Pyridazino[4,5-b]-1,8-naphthyridines, a New Tetraazaheterocyclic System

Juan Vilar, Carlos Peinador, and José M^a Quintela*

*Department of Fundamental Chemistry, Science Faculty, University of A Coruña, Campus A Zapateira, E-15071, A Coruña, Spain

Abstract

A synthesis of the substituted pyridazino[4,5-b]-1,8-naphthyridin-6(7H)-ones (6) based on the reaction of ethyl 2-(dibromomethyl)-6-cyano-7-ethoxy-5-phenyl-1,8-naphthyridine-3-carboxylate (3) with hydrazone or substituted hydrazones is described.

■ Efficient Synthesis of New Potentially Bioactive Tricyclic Pyridinones

Caroline Cstera, Maxime D. Crozet, Michel P. Crozet, and Patrice Vanelle*

*Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, CNRS UMR, University of the Méditerranée (Aix-Marseille 2), 27 Boulevard Jean Moulin, 13385 Marseille cedex 5, France

Abstract

A rapid synthetic route towards new tricyclic pyridinones, from 6-halogeno-3-nitroimidazo[1,2-a]pyridines bearing the diethyl methylenemalonate group at the 2-position or directly from 6-halogeno-3-nitroimidazo[1,2-a]pyridines bearing the diethyl methylmalonate group at the 2-position, is described.

■ Synthesis of Bitriazolyl Compounds via Huisgen Reaction

Yi Xia, Fanqi Qu, Wei Li, Qiongyon Wu, and Ling Peng*

*Département de chimie, AFMB CNRS UMR 6098, Université Aix-Marseille II, 163, avenue de Luminy, 13288 Marseille cedex 09, France

Abstract

Bitriazolyl compounds were synthesized via Huisgen 1,3-cyclcoaddition starting with an azidotriazole and various alkynes. Good yields were obtained with terminal alkynes using copper(I) as a catalyst in the THF/H₂O system.

■ Alumina-Ammonium Acetate as an Efficient Reagent for the One-Pot Synthesis of cis-2,4,5-Triarylimidazolines from Aromatic Aldehydes

Babak Kaboudin* and Fariba Saadati

*Department of Chemistry, Institute for Advanced Studies in Basic Sciences, Gava Zang, Zanjan 45195-159, Iran

Abstract

A simple, efficient, and new method has been developed for the synthesis of 2,4,5-triarylimidazolines from aldehydes through a one-pot reaction of aldehydes in the presence of alumina-ammonium acetate under solvent–free conditions using microwave irradiation. This method is easy, rapid, one-pot and good to high-yielding reaction for the synthesis of 2,4,5-triarylimidazolines.

■ Synthesis and Characterization of a New Series of 3-(4-Antipyrinyl)-2-thiohydantoin Derivatives

Chun-Ming Ma, Jian-Ping Li,* and Peng-Zhi Zheng

*College of Chemistry and Environmental Science, Henan Normal University, Xinxiang, 453007, Henan, China

Abstract

This paper reports the reaction of 4-antipyrinyl isothiocyanate with DL-amino acids affording a new heterocyclic series of 3-(4-antipyrinyl)-2-thiohydantoin derivatives in mild conditions. The reaction proves to be simple and the experiment is easy to operate with high yields (86-96%).

■ Structural Revision of Hemsleyadine and New Alkaloids Hemsleyanines A, B from Aconitum hemsleyanium var. circinacum

Feng Gao and Feng-Peng Wang*

*Department of Chemistry of Medicinal Natural Products, West China College of Pharmacy, Sichuan University, No. 17, Duan 3, Remin Nan Road, Chengdu 610041, China

Abstract

Study on the phytochemistry of Aconitum hemsleyanium var. circinacum led to isolate two new C₁₉-diterpenoid alkaloids, hemsleyanines A (6) and B (7) together with six known alkaloids, yunaconitine, talatisamine, hemsleyadine, hemsleyasine, hemsleyanidine and isohemsleyanidine. The structures of these alkaloids including new alkaloids hemsleynines A and B were established on the basis of spectral data (¹H- and ¹³C- NMR, 2D NMR, HRMS) and X-Ray analysis.

■ Electrochemical Dehydrogenation of 1,2,3,4-Tetrahydroisoquinoline to 3,4-Dihydroisoquinoline

Mitsuhiro Okimoto,* Yukio Takahashi, Kaori Numata, and Gaku Sasaki

*Department of Applied and Environmental Chemistry, Kitami Institute of Technology, Koen-cho 165, Itami, Hokkaido 090-8507, Japan

Abstract

Dehydrogenation of 1,2,3,4-tetrahydroisoquinoline to 3,4-dihydroisoquinoline was carried out using an electrochemical method in the presence of KI. In this method, the iodide ion presumably played an important role as an electron carrier.

■ Syntheses of Pyrrolo- and Furo-1,4-dihydropyridine Derivatives

Keizo Matsuo,* Masami Adachi, Tatsuko Takagi, Sachiko Ueno, Takahiko Arase, and Fumie Kuroi

*Faculty of Pharmaceutical Sciences, Kinki University, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan

Abstract

Methyl 4-aryl-1,4,5,7-tetrahydro-2,7,7-trimethyl-5-oxo-6H-pyrrolo[4,3-b]pyridine-3-carboxylates and methyl 1,4,5,7-tetrahydro-3-methyl-7-oxo-4-phenylfuro[3,4-b]pyridine-3-carboxylate were synthesized. Attempting synthesis of methyl 4-aryl-1,3,5,7a-tetrahydro-1,1,6-trimethyl-3-oxofuro[3,4-c]pyridine-7-carboxylates failed.

■ Fluorinated Heterocyclic Compounds. A Photochemical Approach to a Synthesis of Polyfluoroaryl-1,2,4-triazoles

Silvestre Buscemi,* Andrea Pace, Antonio Palumbo Piccionello, Ivana Pibiri, and Nicolò Vivona

*Dipartimento di Chimica Organica, Università digli Studi di Palermo, Viale delle Scienze, Parco d’Orleans II, 90128 Palermo, Italy

Abstract

The reaction of some fluorinated 1,2,4-oxadiazoles in the presence of methylamine or propylamine has been investigated. The irradiation in methanol or acetonitrile leads with acceptable yields to the corresponding fluorinated 1-methyl- or 1-propyl-1,2,4-triazole.

■ Synthesis of Lupinine

Meng-Yang Chang,* Huo-Mu Tai,* Ching-Han Lin, and Nein-Chen Chang

*Department of Applied Chemistry, National University of Kaohsiung, No. 700 Kaohsiung University Rd., Nan-Tzu District, Kaohsiung 811, Taiwan, R.O.C.

Abstract

A synthesis of lupinine (1a) is performed from 5-amino-1-pentanol in ten steps. The glutarimide (3) was obtained from 1-(5-hydroxypentyl)-2- (4-methylphenylsulfonyl)acetamide (5) and acrylate (4) via a formal [3+3] annulation. This formation of quinolizidine skeleton was established via a key acid-catalyzed cyclization method.

■ Practical Syntheses of the Adhesion Molecule Inhibitor ER-49890 and Its Stereoisomer

Toshihiko Kaneko,* Fumihiro Ozaki, Richard S. J. Clark, Yuki Komatsu, and Kazuo Okano

*Tsukuba Research Laboratories, Eisai Co., ltd., 1-3 Tokodai 5-chome, Tsukuba-shi, Ibaraki 300-2635, Japan

Abstract

Practical synthetic routes to anti-[3-(10H-pyrazino[2,3-b][1,4]- benzothiazin-8-ylmethyl)-3-azabicyclo[3.3.1]non-9-yl]acetic acid (ER-49890, 1) and its syn-isomer are reported. The anti-(3-azabicyclo[3.3.1]non-9-yl)acetic acid side chain (anti-12) was synthesized stereoselectively using Pd/C hydrogenation in the presence of HCl. The syn-isomer (syn-12) was concisely obtained by crystallization as its oxalic acid salt from a 1:1 mixture of anti- and syn-isomers. The 10H-pyrazino[2,3-b][1,4]benzothiazine core (7) was prepared from commercially available 4-chloro-3-nitrobenzyl alcohol (13) in four steps and good yield.

■ Some Aspects of the Willgerodt-Kindler Reaction and Connected Reactions

Giovanni Purrello

*Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy

Abstract

This review presents a discussion, in near chronological order, of the course of Willgerodt–Kindler reactions that occur under different experimental conditions. It is possible to isolate the various intermediates postulated in our initial working hypotheses of these reactions, allowing us to clarify inter alia the course of the isomerization process. Of note, we show that room temperature reactions follows the same reaction pathway as those synthesized under more severe experimental conditions, and this observation allows us to comprehend the chemism of the initial steps of the process.

■ Synthesis and Reactivity of Thioaurones over the Past One Hundred Years

Marek T. Konieczny* and Wojciech Konieczny

*Department of Organic Chemistry, Medical University of Gdansk, Al. Gen. Hallera 107, 80-416 Gdansk, Poland

Abstract

The synthesis and reactivity of 2-benzylidenebenzo[b]thiophen-3(2H)-ones (thioaurones) is comprehensively reviewed.