HETEROCYCLES

■ Contents

■ Synthesis of 2(3H)-Benzoxazolone Derivatives as Potential Melatonin Receptor Ligands

Christophe Mésangeau, Jacques H. Poupaert, Pascal Carato,* and Saïd Yous

*Laboratoire de Chimie Thérapeutique, Faculté des Sciences Pharmaceutiques et Biologiques de Lille, Université de Lille 2, 3, rue du Professeur Laguesse, BP 83, F-59006 Lille, France

Abstract

This article reports the synthesis of new 2(3H)-benzoxazolone-based ligands for the melatonin receptors in which an acetamidopropyl side-chain was incorporated. Construction of the acetamidopropyl moiety was achieved via a Wadsworth-Emmons approach. Although these compounds can be seen as derivatives of N-[3-(3-methoxyphenyl)propyl]acetamide (MPPA), which is the exact analogue of melatonin in which the 1,2-indole nitrogen atoms are deleted, they exhibit lower affinities for the melatonin receptors probably due to an unfavourable steric bulk and hydrophilic interactions

■ One Pot Syntheses of Substituted Naphthyridines and 2H-Pyrano[3,2-g]quinolin-2-ones in Water

Noé Rosas,* Pankaj Sharma, Armando Cabrera, Guillermo Pénieres, José L. García, and Luis A. Maldonado

*Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitatria, Coyoacán 04510, Mexico

Abstract

One pot catalytic syntheses of substituted 1,8-naphthyridines and 2H-pyrano[3,2-g]quinolin-2-ones by the reaction of α-ketoalkynes with 6-aminonicotinamide and 7-amino-4-methylcoumarin respectively in water, using a homogeneous nickel catalyst at very mild reaction conditions are described. In the absence of this catalytic system very low yields are obtained even after long reaction time.

■ Stereoselective Intramolecular Azide 1,3-Dipolar Cycloaddition

Theodoros Markidis, Emmanuel Mikros, and George Kokotos*

*Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Athens 15771, Greece

Abstract

Ethyl (E)-7-azido-6-[bis(tert-butoxycarbonyl)amino]-2-heptenoate undergoes a stereoselective intramolecular azide 1,3-dipolar cycloaddition leading to a stable triazoline. The configuration and the conformation of the triazoline obtained were determined by spectroscopic data and confirmed by molecular mechanics calculations.

■ Synthesis and X-Ray Analysis of New 1,5-Benzodiazepinium Picrates

Andreas Schmidt,* Abbas Gholipour Shilabin, and Martin Nieger

*Institut für Organische Chemie, Technische Universität Clausthal, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany

Abstract

1,2-Diaminobenzenes react with pentane-2,4-dione in ethanol in the presence of picric acid to give 1,5-benzodiazepinium picrates. In the single crystal, the benzodiazepinium molecules form layers with overlapped 7-membered rings in head-to-tail arrangement. Hydrogen bonds to the picrate connect the 1,5-benzodiazepinium molecules of two layers.

■ Selective Nucleophilic Substitutions on Tetrazines

Zoltán Novák, Beatrix Bostai, Márton Csékei, Krisztián Lörincz, and András Kotschy*

*Department of General and Inorganic Chemistry, Eötvös Loránd University, Pázmány Péter s. 1/A, H-1117 Budapest, Hungary

Abstract

A series of tetrazine derivatives bearing a leaving group were reacted with different nucleophiles to undergo either the expected substitution reaction or an unexpected exchange of the other substituent of the tetrazine ring selectively. The influence of the choice of nucleophile as well as the substituents on the tetrazine was examined in detail and the interpretation of the results was also supported by quantum chemical calculations.

■ A New Tetracyclic Ring System of Biological Interest. Indolo[3,2-e][1,2,3]triazolo[1,5-a]pyrimidines through Domino Reactions of 2-Azidoindole

Antonino Lauria, Chiara Patella, Patrizia Diana, Paola Barraja, Alessandra Montalbano, Girolamo Cirrincione, Gaetano Dattolo, and Anna Maria Almerico*

*Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy

Abstract

Derivatives of the new ring system indolo[3,2-e][1,2,3]triazolo[1,5-a]pyrimidine were easily prepared from 2-azidoindole (7) and substituted acetonitriles. Such a cycliczation represents the first example of an anionic domino reaction in the indole series. The tetracycle of type (10) presents suitable requirements to interact with DNA.

■ Synthesis of 2H-1,2,3-Triazolo[4,5-d]pyrimidine-5,7-diones from Uracils Using Cyclization Reaction of β-Azo-α,β-unsaturated Sulfilimines

Nobuaki Matsumoto and Masahiko Takahashi*

*Department of Materials Sciences, Faculty of Engineering, Ibaraki University, 4-12-1 Nakanarusawamachi, Hitachi, Ibaraki 316-8511, Japan

Abstract

N-(Uracil-6-yl)-S,S-diphenylsulfilimine (1) prepared from uracils reacted with aryldiazonium salts to give N-(5-arylazouracil-6-yl)-S,S-diphenylsulfilimines (2), β-azo-α,β-unsaturated sulfilimines, in good yields. The azo sulfilimines (2) were converted on thermolysis into the corresponding 2H-1,2,3-triazolo[4,5-d]pyrimidine-5,7-diones (3) in good yields.

■ Nuclear Magnetic Resonance Spectroscopical Studies of 2-Carbonyl Derivatives of Five-membered Monoheterocycles and Determination of Aromaticity Indices

Kyu Ok Jeon, Ji Sook Yu, and Chang Kiu Lee*

*Department of Chemistry, Kangwon National University, Chuncheon 200-701, Korea

Abstract

¹H And ¹³C chemical shifts of formyl, acetyl, benzoyl, and methoxycarbonyl derivatives of benzene, thiophene, pyrrole and furan in chloroform-d, methanol-d₄, and DMSO-d₆ are examined. Deviation of the signals of the ring protons and carbonyl carbons provide bases for estimating the indices of aromaticity of the heterocycles. The exceptionally large carbonyl stretching vibration of furan derivatives and correlations of the stretching frequencies with the reactivities of the carbonyl groups are discussed.

■ Enantioselective Synthesis of the Tetrahydrobenzylisoquinoline Alkaloid (-)-Norarmepavine Using Polymer Supported Reagents

Ian R. Baxendale, Thomas D. Davidson, Steven V. Ley, and Remedios H. Perni*

*Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, U.K.

Abstract

We describe, in full, the enantioselective synthesis of the tetrahydrobenzylisoquinoline alkaloid (-)-norarmepavine (1) in 77% e.e. This compound was prepared using solid-supported reagents and scavengers in multi-step sequences of reactions to give materials that required no conventional purification at the individual steps.

■ Catalytic Hydrogenation of 8-Acyloxy-1-cyanoisoquinoline and Synthesis of 9-Methoxy-9-deethoxycribrostatin 6

Shinsuke Nakahara* and Akinori Kubo

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

Abstract

Catalytic hydrogenation of 8-acyloxy-1-cyanoisoquinolines (6)Å`(9) in the presence of 10% Pd-C and synthesis of 9-methoxy isomer (10) of cribrostatin 6 utilizing the compound (26) obtained by this reaction are described.

■ Synthesis of Pyridopyrrolo[2,1-a]isoindoles by Palladium-catalyzed Annulation

Song Su Kang, Eul Kgun Yum,* and Nack-Do Sung

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

Abstract

Diverse pyridopyrrolo[2,1-a]isoindoles were prepared by palladium-catalyzed annulation of benzylidene(4-iodopyridin-3-yl)amines and aromatic substituted internal alkynes under Pd(OAc)₂, n-Bu₄NCl, and Et₃N at 110 °C.

■ Preparation of 2’-3’-Epimino-carbocyclic Nucleosides Based on 2-Azabicyclo[2.2.1]hept-5-en-3-one

Minoru Ishikura,* Kota Matsumoto, Miyako Hasunuma, and Nobuya Katagiri

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

Abstract

The thermal reaction of N-substituted 2-azabicyclo[2.2.1]hept-5-en-3-one (ABH) (1) with tosyl azide, which allowed the stereoselective introduction of an aziridine moiety into ABH (1), led to the facile construction of 6-azabicyclo[3.1.0]hexane (3). Successful conversion of 3 to the hitherto unknown 2’,3’-epimino-carbocyclic nucleosides (8) could be attained through a series of steps.

■ New Chiral Synthesis of Methyl and Allyl Disubstituted Butyro Lactone: A Formal Synthesis of (-)-Ngaione

Katsufumi Suzuki, Kohei Inomata,* and Yasuyuki Endo

*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

A new chiral synthesis of butyrolactone [(-)-7] bearing methyl and allyl substituents at the γ-position has been established via diastereoselective continuous nucleophilic addition to the chiral tricyclic lactone [(-)-1] as the key step. In practice, continuous nucleophilic addition to the tricyclic lactone [(-)-1] by using the combination of methyllithium and allylmagnesium bromide proceeded to yield the corresponding diol (8) diastereoselectively. After oxidation of 8, enantiopure methyl and allyl disubstituted butenolide (10) was obtained via retro-Diels-Alder reaction. Selective 1,4-reduction of 10 afforded the corresponding butyrolactone [(-)-7], which is the key intermediate for (-)-ngaione synthesis.

■ Synthesis of 1,4,6-Trisubstituted 2[1H]-Pyrimidineselenones

Alicja Zylewska,* Waldemar Tejchman, Maria J. Korohoda, and Marek Zylewski

*Department of Chemistry, Pedagogical University, Podchorazych St. 2, PL-30084 Kraków, Poland

Abstract

1,6-Diaryl-4-methyl-2[1H]-pyrimidineselenones and 1,4-diaryl-6-methyl-2[1H]-pyrimidineselenones were synthesised by treatment of appropriate pyrimidinethiones with gaseous H₂Se. 2D NMR spectroscopic studies were conducted to obtain conformations of the newly synthesised derivatives

■ Synthesis of 5-Substituted Indole Derivatives, Part 5. A Synthesis of 5-Formyl-1H-indole-2-carboxylates: The CH₂SO₃H Functionality as a Masked Formyl Group

Béla Pete,* Gyula Parlagh, and László Töke

*Department of Organic Chemical Technology, Technical University of Budapest, H-1521 Budapest, Gellért tér 4, Hungary

Abstract

New synthetic intermediates, ethyl 5-formyl-1H-indole-2-carboxylates (4) were prepared from 2-ethoxycarbonyl-1H-indole-5-methanesulfonic acids (1). The transformation of the sulfomethyl group to formyl function was accomplished through elimination of SO₂ to yield ethyl 5-chloromethyl-1H-indole-2-carboxylates (2), hydrolysed to ethyl 5-hydroxymethyl-1H-indole-2-carboxylates (3), then oxidized to aldehydes (4).

■ Four New Isoflavonoids and a New 2-Arylbenzofuran from the Roots of Erythrina variegata

Hitoshi Tanaka,* Miyuki Hirata, Hideo Etoh, Magoichi Sako, Masaru Sato, Jin Murata, Hiroko Murata, Dedy Darnaedi, and Toshio Fukai

*Faculty of Pharmacy, Meijo University, 150 Yagoto, Tempaku-ku, Nagoya, Aichi 468-8503, Japan

Abstract

Four new isoflavonoids, eryvarins H-K, and a new 2-arylbenzofuran, eryvarin L, together with five known compounds, were isolated from the roots of Erythrina variegata. Their structures were established on the basis of spectroscopic analysis. Eryvarins H and I are rare naturally-occurring isoflav-3-enes. The antibacterial activity of these five new compounds against 13 strains of methicillin-resistant Staphylococcus aureus (MRSA) was examined.

■ Improved, Rapid and Efficient Synthesis of Polymethoxyflavones under Microwave Irradiation and Their Inhibitory Effects on Melanogenesis

Masao Tsukayama,* Yasuhiko Kawamura, Takaaki Ishizuka, Shinji Hayashi, and Fumihito Torii

*Department of Chemical Science and Technology, Faculty of Engineering, University of Tokushima, Minamijosanjima-cho, Tokushima 770-8506, Japan

Abstract

The microwave-assisted methylation of 2,5-dihydroxy-1,3-dimethoxybenzeneÅ@with (CH₃O)₂SO₂ for 5 min gave easily 1,2,3,5-tetramethoxybenzene, which was converted into pentamethoxybenzene. The microwave-assisted Friedel-Crafts acylation of pentamethoxybenzene in the presence of In(CF₃SO₃)₃ gave pentamethoxyacetophenone for 15 min under solvent-free conditions in high yield. The microwave-assisted cyclization reaction of the diketones, which were synthesized from the acetophenone via three steps under microwave irradiation, gave the desired polymethoxyflavones for 1.5-3 min in high yields. The polymethoxyflavones showed inhibitory effects on melanogenesis in a human melanoma.