HETEROCYCLES

■ Contents

■ A Facile Method for Conversion of Phenolic Tetrahydroisoquinolines to Benzylamines with Ring Cleavage

Takashi Nakata, Naho Komatsu, Mamiko Yamanaka, Hae Joo Lee, Yutaka Matsuoka, Kiyoshi Nishitani, Miyuki Ishizaki, and Hiroshi Hara*

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

Abstract

The reaction of N-cyanomethyl-6- and -8-hydroxytetrahydroiso-quinolinium methiodide with various amines afforded the corresponding benzylamines via the formation of p- or o-quinone methide in moderate to high yields.

■ Synthesis and Antitumor Activity of 2-Aryl-7-fluoro-6-(4-methyl-1-piperazinyl)-4(3H)-quinazolinones

Raid J. Abdel-Jalil,* Hani M. Aldoqum, Mikdad T. Ayoub, and Wolfgang Voelter*

*Abteilung für Physikalische Biochemie, Physiologisch-chemisches Institut, Universität Tübingen, Hoppe-Seyler-Sraβe 4, D-72076 Tübingen, Germany

Abstract

A series of new 2-aryl-7-fluoro-6-(4-methyl-1-piperazinyl)-4(3H)-quinazolinones were prepared by the oxidative cyclization of the corresponding 2-arylidineamino-4-fluoro-5-(4-methyl-1-piperazinyl)benzamides. The new quinazolinones were evaluated for their antitumor activity.

■ Nucleophilic Substitution Reaction of Amines with 3-Bromo-4-nitropyridine (and 2-Nitropyridine): A New Nitro-group Migration

Jiangchao Yao,* Paul R. Blake, and Ji Yang

*Computational, Combinatorial, and Medicinal Chemistry Department, Discovery Research, Purdue Pharma L.P., 6 Cedar Brook Drive, Cranbury, NJ 08512, U.S.A.

Abstract

On the reaction 3-bromo-4-nitropyridine with amine, three in stead of two expected products are separated. 2D NMR spectral data indicate the major product was an unexpected nitro-group migration product. To explore the rearrangement mechanism, a systematic study with various solvents and bases was undertaken. Results obtained indicate that nitro-group migration occurs in polar aprotic solvents; while expected nucleophilic substitution took place under all tested conditions.

■ Briviolides, New Briarane Diterpenes from a Gorgonian Briareum Sp.

Tetsuo Iwagawa,* Kazutaka Babazono, Hiroaki Okamura, Munehiro Nakatani, Matsumi Doe, Yoshiki Morimoto, Motoo Shiro, and Kaoru Takemura

*Department of Chemistry and Bioscience, Faculty of Science, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan

Abstract

Further investigation of a gorgonian Briareum sp., collected in the area of Bonotsu, Kagoshima Prefecture, afforded thirteen new briarane diterpenes. Their structural elucidation and cytotoxicity tests toward Vero and MDCK cells were performed.

■ Facile Synthesis of 3-Substituted and 1,3-Disubstituted Quinolin-2(1H)-ones from 2-Nitrobenzaldehydes

Kwanghee Koh Park* and Jin Young Jung

*Department of Chemistry, Chungnam National University, Yusung, Daejon 305-764, Korea

Abstract

2-Nitrobenzaldehydes were reduced with iron powder to 2-aminobenzaldehydes, which were reacted immediately with acyl chlorides to provide 2-carboxamidobenzaldehydes (1) with overall yields of 71-90 %. Reaction of 1 with base provided 3-substituted quinolin-2(1H)-ones with 63-97 % yields. Treatment of 1 with methyl iodide and base gave 1-methyl-3-substituted quinolin-2(1H)-ones with 82-95 % yields, whereas the treatment with isopropyl iodide gave 1-isopropyl-3-substituted quinolin-2(1H)-ones with 7-42 % yields.

■ Synthesis of 1-Deoxymaxacalcitol

Tsuyoshi Yamauchi,* Masahiro Kato, Tetsuhiro Mikami, and Yasuo Fujimura

*Pre-Clinical Research Department I, Fuji-gotemba Research Laboratories, Chugai Pharmaceutical Company, Ltd., 135, 1-Chome Komakado, Gotemba City, Shizuoka 412-8513, Japan

Abstract

1-Deoxymaxacalcitol, the 1-deoxygenated derivative of maxacalcitol practically used for the treatment of secondary hyperparathyroidism and psoriasis, has been synthesized for the biological evaluation. Although purification of the key intermediate containing 1,3-cyclohexadiene moiety was extremely difficult owing to inseparable contaminants, treatment of the mixture with the heterocyclic dienophile 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) formed the readily separable Diels-Alder adduct from which the target 1-deoxymaxacalcitol could be obtained in a pure state.

■ One-Pot Synthesis of 2-Aryl- and 2-Alkylbenzothiazoles under Microwave Irradiation

Sukanta Kamila, Hongming Zhang, and Edward R. Biehl*

*Chemistry Department, Southern Methodist University, Dallas, TX 75275-0314, U.S.A.

Abstract

Eco-friendly direct solvent-free reactions of o-aminothiophenol and aromatic or aliphatic β-keto esters with microwave irradiation produced 2-substituted benzothiazoles in excellent yield. Experiments that compared microwave irradiation to conventional heating methods showed that the former gives the 2-substituted benzothiazoles faster and in higher yields. The formation of the titled compounds probably involves the nucleophilic addition of the thiol group to the keto group of the β-keto ester with subsequent elimination of ethyl acetate from the resulting adduct. The adduct then undergoes an intramolecular addition of the o-amino group to the carbonyl group to give an adduct from which water is eliminated to afford the 2- substituted benzothiazoles.

■ Chemoenzymatic Synthesis of Naturally Occurring (Z)-3-Hexenyl 6-O-Glycosyl-β-D-glucopyranosides

Masashi Kishida, Mikio Fujii, Yoshiteru Ida, and Hiroyuki Akita*

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

Abstract

Direct β-glucosidation between cis-3-hexen-1-ol and D-glucose (5) using the immobilized β-glucosidase from almonds with the synthetic prepolymer ENTP-4000 gave (Z)-3-hexenyl β-D-glucoside (1) in 17% yield. The coupling of the (Z)-3-hexenyl O-β-D-glucopyranoside congener (7) with 2,3,4-tri-O-benzoyl-α-D-xylopyranosylÅ@bromide (8) gave the coupled product (11). Similarly the coupling of 7 with 2,3,4-tri-O-benzoyl-α-L-arabinopyranosyl bromide (9), and that of 7 with 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl bromide (10) afforded the coupled products (12 and 13), respectively. Deprotection of the products (11, 12, and 13) afforded (Z)-3-hexenyl O-β-D-xylopyranosyl-(1Å®6)-β-D-glucopyranoside (2), (Z)-3-hexenyl O-α-L-arabinopyranosyl-(1Å®6)-β-D-glucopyranoside (3), and (Z)-3-hexenyl O-α-L-rhamnopyranosyl- (1Å®6)-β-D-glucopyranoside (4), respectively.

■ Acid Catalyzed Cyclization Reaction of 3-Hydrazono-1,1,1-trifluoro-2-alkanones to 6-Trifluoromethyl-3,6-dihydro-2H-[1,3,4]oxadiazines

Yasuhiro Kamitori* and Tomoko Sekiyama

*Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

Mechanisms for the acid catalyzed cyclization reaction of 3- dialkylhydrazono-1,1,1-trifluoro-2-alkanones (1) to 6-trifluoromethyl-3,6-dihydro-2H- [1,3,4]oxadiazines (2) are discussed. The results indicate 1,5-sigmatropic shift of hydrogen atom from N-methyl group to carbonyl carbon center on protonated 1 to be a key step for this cyclization reaction.

■ Sulfur Ylides in Reactions with 5-X-Adamantan-2-ones. Stereochemistry and Reactivity

Giada Catanoso, Barbara Di Credico, and Elisabetta Vecchi*

*Department of Chemistry, C. N. R. Institute of Biomolecular Chemistry - Roma Section, University “La Sapienza”, Piazzale Aldo Moro 5, I-00185 Roma, Box 34 Roma 62, Italy

Abstract

This work describes the stereochemistry and the relative rates of epoxidation reactions of the title compounds with sulfur ylides (methylenedimethylsulfurane and methylenedimethyloxysulfurane) in DMSO and C₆H₆. The electronic perturbative effect of substituent X depends on the solvent and on the reactant. It is transmitted in opposite way in solvents of different polarity depending on the reactant. The electronegativity of the substituent scarcely affects the percentages of axial/equatorial attack. The percentage of equatorial attack with methylenedimethyloxysulfurane is markedly lower for 5-X-adamantan-2-ones than for 4-X-cyclohexanones.

■ Reaction of Some Furan-2,3-diones with Various 1,2-Phenylenediamines

Emin Saripinar,* Ertugrul Gazi Saglam, Ibrahim Öncel, Ilhan Özer Ilhan, Lale Göktas, Tevfik Riza Kök, and Yunus Akçamur

*Department of Chemistry, Arts and Sciences Faculty, Erciyes University, TR-38039 Kayseri, Turkey

Abstract

Condensation of 4-aroyl-5-aryl-2,3-furandiones (1a,b) and ethyl 4,5-dioxo-2-phenyl-4,5-dihydrofuran-3-carboxylate (1c) with various 1,2-phenylenediamines (2d-f) gave 2(1H)-quinoxalinone derivatives, 1,3-diaryl-2-(3-oxo-3,4-dihydro-2-quinoxalinyl)-1,3-propanediones (3ae,af,bd,be,bf) and ethyl 3-aryl-3-oxo-2-(2-oxo-1,2-dihydro-2-quinoxalinyl)propanoate (3cd,ce). Alkaline treatment of 1,3-propanediones (3af,bd,bf) gave corresponding 3-aroylmethyl-2(1H)-quinoxalinones (4af,bd,bf).

■ Pinene-fused Chiral N-Ethylpyridinium Room Temperature Molten Salts

Dusan Drahonovsky, Gaël Charles Labat, Juraj Sevcík, and Alex von Zelewsky*

*Department of Chemistry, University of Fribourg, 9 Ch. du Musée, CH-1700 Fribourg, Switzerland

Abstract

New chiral room temperature molten salts (ionic liquids) based on the pinene-pyridinium unit associated with triflate or trifluoroacetate anions were prepared. The thermal behavior of these salts was observed by DSC and solventless ¹H NMR spectrum, whereas the diastereomeric interactions were studied by test asymmetric reactions, GC, CD spectroscopy, and ¹⁹F NMR spectra. X-Ray structure of iodide intermediate is presented.

■ Catalytic Aromatization of Hantzsch 1,4-Dihydropyridines by Bis(salicylaldehyde-1,2-phenylenediimine) Mn(III) Chloride Using Urea Hydrogen Peroxide as Mild and Efficient Oxidant

Bahador Karami,* Morteza Montazerozohori, and Masoud Nasr-Esfahani

*Department of Chemistry, Yasouj University, Yasouj 75914-353, Iran

Abstract

A variety of Hantzsch 1,4-dihyropyridines were oxidized efficiently by a catalytic amount of bis(salcylaldehyde-1,2-phenylenediimine)Mn(III) chloride (Mn(III)-salophen I) in the presence of urea hydrogen peroxide adduct (UHP II) as convenient and mild oxidant to afford the related pyridine derivatives in high yields at room temperature.

■ Preparation of 1-Alkyl-2-aryl-1H-imidazo[4,5-b]pyridines from 2-Alkylamino-3-aminopyridines and Aromatic Aldehydes Using Air as an Oxidant

Mikhail Krasavin,* Vladimir V. Kobak, Tatiana Y. Bondarenko, and Dmitry V. Kravchenko

*Chemical Diversity Research Institute, 2a Rabochaya St., Khimki, Moscow reg., 114404, Russia

Abstract

Attempted imine formation between 2-methoxyethylamino-3-aminopyridine (an exemplary 2-alkylamino-3-aminopyridine) and an array of aromatic aldehydes in methanol and ambient atmosphere led to the predominant formation of 1-methoxyethyl-2-aryl-1H-imidazo[4,5-b]pyridines. The reaction was found to be of immediate preparative importance in the six cases studied.

■ Synthesis of New 3-Hydroxy-4(1H)-pyridinone Directly Attached to Quinoxaline and Its Fluorescence Property upon Complexation to Metal Ions

Akira Katoh,* Kenichi Ogino, and Ryota Saito

*Department of Materials and Life Science, Faculty of Science and Technology, Seikei University, Musashino-shi, Tokyo 180-8633, Japan

Abstract

A new fluorophore (3), in which the bidentate ligand, 3-hydroxy-2-methyl-4(1H)-pyridinone is directly attached to the fluorescent 2,3-dimorpholino-quinoxaline at C-6 position. The bidentate ligand (3) formed 3:1 complexes with Fe(III), Al(III), Ga(III), and Cr(III). The fluorescence was efficiently quenched by the metal complex formation via the Perrin model of static quenching, the quenching efficiency being in order of Fe(III) >> Al(III) > Ga(III) > Cr(III). The fluorescence was recoverd by removal of Fe(III) with the N-benzoyl analogue of a naturally occurring siderophore, desferrioxamine B.

■ Luotonin A: A Lead toward Anti-Cancer Agent Development

Zhongze Ma,* Yoshio Hano,* and Taro Nomura

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

Abstract

Luotonin A, a novel pyrroloquinazolinoquinoline alkaloid isolated from the aerial parts of Peganum nigellastrum Bunge, showed a cytotoxic activity against mouse leukemia cells (P-388) and an inhibitory activity against topoisomerase I and II. This review covers the isolation, structural determination, synthesis and biological activity of luotonin A and its related derivatives. A water-soluble topoisomerase I inhibitor, 14-azacamptothecin analogous to luotonin A and camptothecin, was also discussed.

■ Photochemical Addition Reactions Involving Phthalimides

Gerard McDermott, Dong Jin Yoo, and Michael Oelgemöller*

*School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland

Abstract

This review summarizes photochemical addition reactions involving the phthalimide system from the pioneering work of Y. Kanaoka in the early 1970’ies to recent developments. Photoadditions of arenes, alkenes, alcohols, ethers, amines, thioethers, carboxylates and α-trialkylsilylmethyl-substituted compounds are described.