HETEROCYCLES

■ Contents

■ Preparation of Chiral 5,6-trans-Disubstituted Phenanthrolines from Phenanthroline-5,6-epoxide

Elke Schoffers,* Son Duc Tran, and Kristen Mace

*Western Michigan University, Chemistry Department, 3425 Wood Hall, KalamazooMI 49008-5413, U.S.A.

Abstract

A new preparative route to chiral aminoalcohol derivatives of 5,6-dihydro-1,10-phenanthroline is described. Ring opening of 1,10-phenanthroline-5,6-epoxide (1) with a variety of nitrogen nucleophiles was accomplished using magnesium perchlorate as an effective Lewis acid and compared to reactions catalyzed by alumina.

■ [2π + 2σ] Type Cycloaddition Reactions of Naphtho[b]cyclopropene with Imine or Carbonyl Derivatives Conjugated with Heteroaromatic Ring to Form Naphtho[b]dihydropyrroles or Furans

Katsuhiro Saito,* Katsuhiko Ono, Masakazu Ohkita, Machiko Fukaya, Kotaro Ono, and Yoji Kondo

*Nagoya Institute of Technology, Department of Applied Chemistry, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan

Abstract

Imine derivatives conjugated with heteroaromatic ring such as furan, thiophene or pyrrole reacted with naphtho[b]cyclopropene in the presence of silver or ytterbium catalysts. The reactions proceeded via [2π + 2σ] type cycloaddition process to give naphtho[b]dihydropyrrole derivatives. The yields of the cycloadducts were influenced by the heteroaromatic ring, i.e. the furan derivatives gave high yields and the pyrrole derivatives gave low ones. The effects of the catalysts and the solvents were also investigated. The analogous reactions with heterocyclic aldehydes gave naphtho[b]dihydrofuran derivatives. Furthermore, a reaction with a hydrazone derivative afforded an open chain type adduct.

■ Size Selective Recognition of Anions by a Tetracationic Imidazoliophane

Kiyoshi Sato,* Tomomi Onitake, Sadao Arai, and Takamichi Yamagishi

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

Abstract

The reaction of 1:1 mixture of 1,3-bis(1-imidazolyl)propane and 1,4-bis(chloromethyl)durene gives a new tetracationic heterophane (2), which forms a 1:1 inclusion complex with halides and oxoanions in DMSO-d₆ in the order of HSO₄^- > Br^- > H₂PO₄^- > Cl^- > I^- > ClO₄^- depending on the size of anions.

■ π-Facial Selectivity in Diels-Alder Reactions of Cross-conjugated Ketones Bearing an Oxa-spiro-ring with Sterically Undemanding Dienes

Ryukichi Takagi, Wataru Miyanaga, Yukiko Tamura, Satoshi Kojima, and Katsuo Ohkata*

*Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan

Abstract

The Diels-Alder reactions of cross-conjugated ketones bearing an oxa-spiro-ring with some simple sterically undemanding dienes (cyclopentadiene, 2,3-cyclohexadiene, 2,3-dimethyl-1,3-butadiene) afforded the adduct with high π-facial selectivity under mild conditions. The π-facial selectivity can be explained in terms of Cieplak model.

■ Synthesis of Chiral 3,4-Disubstituted Pyrroles from L-Amino Acids

Jocelyn A. Hover, Charles W. Bock, and Krishna L. Bhat*

*Department of Chemistry and Biochemistry, School of Science and Health, Philadelphia University, Philadelphia, PA 19144, U.S.A.

Abstract

A general methodology for the conversion of naturally occurring amino acids to 3,4-disubstituted pyrroles is described. A suitably protected amino acid (1) was first converted to the corresponding aldehyde (2). Horner-Emmons olefination afforded a facile entry to the corresponding α,β-unsaturated ester (3). The construction of the pyrrole ring system was accomplished in a single step, using an intramolecular cyclization reaction with tosylmethyl isocyanide (TOSMIC).

■ A New Synthesis of 4-Alkyl/aryl-5,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5-diones and Molecular Rearrangement of Their 3-Bromo Derivatives to 2-Alkyl/aryl-4-oxo-4,5-dihydrofuro[3,2-c]quinoline-3-carboxylic Acids

Antonín Klásek,* Kamil Koristek, Petr Sedmera, and Petr Halada

*Department of Chemistry and Environmental Technology, Faculty of Technology, Tomas Bata University, 762 72 Zlín, Czech Republic

Abstract

The treatment of 3-acyl-4-hydroxy-1H-quinolin-2-ones (1) with ethyl (triphenylphosphoranylidene)acetate leads to 5,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5-diones (2), which were brominated to 3-bromo derivatives (4). Alkaline hydrolysis of 4 gives 2-alkyl/aryl-4-oxo-4,5-dihydrofuro[3,2-c]quinoline-3-carboxylic acids (6), which were decarboxylated to 2-alkyl/aryl-5H-furo[3,2-c]quinolin-4-ones (8). The reaction of 3-acetyl-4-hydroxy-1-methyl-1H-quinolin-2-one (1a) with ethyl (triphenylphosphoranylidene)chloroacetate proceeds not only at the acetyl but also at the amide group to give a mixture of ethyl 3,5-dimethyl-4-oxo-4,5-dihydrofuro[3,2-c]quinoline-2-carboxylate (11a) and ethyl 4,6-dimethyl-2-oxo-5,6-dihydro-2H-pyrano[3,2-c]quinolin-5-ylidene-(chloro)acetate (12a). The reaction mechanism of the molecular rearrangement of 4 to 6 is discussed.

■ Regioselective Synthesis of Demethoxyisoacronycine Involving Nucleophilic Addition to Benzyne

Mónika Rudas, Miklós Nyerges,* László Tõke, and Paul W. Groundwater

*Research Group of the Hungarian Academy of Sciences, Department of Organic Chemical Technology, Technical University of Budapest, H-1521 Budapest, P.O.B. 91, Hungary

Abstract

Demethoxyisoacronycine (12) has been prepared in seven steps using the nucleophilic addition of aniline derivative (4) to benzyne (5) as a key step.

■ Benzopyrans. Part 44. Synthesis of 3-(4-Oxo-4H-1-benzopyran-2-yl)indolizines

Chandra Kanta Ghosh,* Sumit Kumar Karak, and Amarendra Patra

*Department of Biochemistry, CalcuttaUniversity, Kolkata 700019, India

Abstract

The pyridinium methylid (5), generated from 1-(4-oxo-4H-1-benzopyran-2-yl)methylpyridinium iodide (4) in the presence of a base, undergoes [3+2] cycloaddition with dimethyl acetylenedicarboxylate and ethyl propiolate, the cycloadducts rapidly aromatising to the indolizines (8) and (9), respectively. Similar cycloaddition of 5 with ethyl acrylate and acrylonitrile is also followed by dehydrogenation giving respectively the indolizines (9) and (10).

■ Synthesis and Biological Evaluation of Triazolo[4,5-g]quinolines, Imidazo[4,5-g]quinolines and Pyrido[2,3-g]quinoxaline. Part II

Antonio Carta,* Gianpiero Boatto, Giuseppe Paglietti, Graziella Poni, Maria Giovanna Setzu, and Paolo Caredda

*Department of Medicinal and Toxicological Chemistry, University of Sassari, Via Muroni 23, 07100 Sassari, Italy

Abstract

Synthesis of triazolo[4,5-g]quinolines, imidazo[4,5-g]quinolines and pyrido[2,3-g]quinoxaline has been described. Antimycobacterial, antibacterial and antimycotic activity were also reported. Compounds (14) and (IIb) exhibited an interesting antimycobacterial activity (against M. tuberculosis and M. smegmatis).

■ Control of the Fading Properties of Photochromic 3,3-Diaryl-3H-naphtho[2,1-b]pyrans

Christopher D. Gabbutt, B. Mark Heron,* and Alicia C. Instone

*Department of Colour Chemistry, The University of Leeds, Leeds, LS2 9JT, U.K.

Abstract

The synthesis and spectroscopic properties of some novel photochromic 3H-naphtho[2,1-b]pyrans are reported. Varying the size of an ortho-substituent on one of the geminal aryl rings allows the rate of fade of the photogenerated color to be controlled.

■ Diastereoselective Synthesis and Structure of Spirooxindole Derivatives

Francesco Risitano,* Giovanni Grassi, Francesco Foti, Giuseppe Bruno, and Archimede Rotondo

*Dipartimento di Chimica Organica e Biologica, Università, Vill. S. Agata, I-98166 Messina, Italy

Abstract

Spiroindolinonisoxazolines (4 and 5h) are prepared from (E)- 1 or (Z)-3-arylidene-2-oxindoles (2) by nitrile oxide cycloaddition reactions. Only one regioisomer is detected in all cases, and the observed complete diastereoselection is established by unambigous structural assignments.

■ Synthesis of New Melatonin Analogues from Dimers of Azaindole and Indole by Use of Suzuki Homocoupling

Jérôme Guillard, Carlos Larraya, and Marie-Claude Viaud-Massuard*

*EA 3247 GRCHT Laboratoire de Chimie Organique, UFR des Sciences Pharmaceutiques, Université de Tours, 31 Avenue de Monge, 37200 Tours, France

Abstract

N-{2-[3’-(2-Acetylaminoethyl)-1H,1’H-[5,5’]biindol-3-yl]- and N-{2-[1’-(2-acetylaminoethyl)-1’H-[5,5’]biindol-1-yl]ethyl}acetamide (2,3) and their analogues in 7-azaindole series (4,5) were synthesized by palladium catalysed reaction starting from indole or 7-azaindole using [1,1’-bis(diphenylphosphino)ferrocene]dichloropalladium, as catalyst.

■ Ethyl Vinyl Ether - an Agent for Protection of the Pyrazole NH-Fragment. A Convenient Method for the Preparation of N-Unsubstituted 4-Alkynylpyrazoles

Sergei F. Vasilevsky,* SvetlanaV. Klyatskaya, Eugene V. Tretyakov, and José Elguero*

*Instituto de Química Médica, C. S. I. C., Juan de Cierva, 3, E-28006 Madrid, Spain

Abstract

N-Unsubstituted 4-iodopyrazole (1) is easily converted into 4-alkynyl derivatives (5) in moderate to good overall yields by using intermediate protection of the nitrogen atom of the pyrazole ring by ethyl vinyl ether.

■ Dopamine/Serotonin Receptor Ligands VI. Dibenz[g,j]-1-oxa-4-azacycloundecene and Dibenz[d,g]-2-azacycloundecene: Synthesis of Two New Heterocyclic Ring Systems as Potential Ligands for Dopamine Receptor Subtypes

Thomas W. Wittig, Christoph Enzensperger, and Jochen Lehmann*

*Institute of Pharmacy, Friedrich-Schiller-University of Jena, Philosophenweg 14, D-07743 Jena, Germany

Abstract

2-(2-Hydroxyethyl)-N-[2-phenoxyethyl]benzamides and 2-(2-hydroxyethyl)-N-[2-phenylpropyl]benzamides have been prepared from 2-phenoxyethyl- or 2-phenylpropylamines and isochroman-1-one. Applying Bischler-Napieralski reaction, a tetracyclic isoquinolino[2,1-d][1,4]benzoxazepine and a isoquinolino[1,2-a][2]benzazepine could be obtained. The titled compounds representing novel 11 membered heterocycles could be prepared by subsequent ring cleavage under Birch conditions after quaternisation with methyl iodide. They are considered to be ligands for dopamine receptors. NMR spectral data indicate different conformations for the two azacycloundecene derivatives.

■ A New Method for Synthesis of Crown Ether Type Pyridinophanes

Masayuki Sato,* Tsunehisa Oda, Ken-ichi Iwamoto, and Satoshi Fujii

*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan

Abstract

Bis(acylketene) (3) thermally generated from Meldrum’s acid derivative (2) underwent intramolecular [4+2] cycloaddition to produce bridged dehydroacetic acid derivative (4). Heating 4 with methylamine and ammonia afforded crown ether type pyridinophanes (5) and (6) (12-crown-4), respectively. Reaction of the ketene (3) with (ethylene glycol)s afforded macrolactones (11-13) in satisfactory yields. Molecular structures of 4 and 6 are discussed based on X-Ray crystallographic analysis.

■ Two New Constituents from the Bark of Holarrhena pubescens

Bina Shaheen Siddiqui,* Shahid Bader Usmani, Syed Tahir Ali, Sabira Begum, and Ghazala H. Rizwani

*H. E. J. Research Institute of Chemistry, International Centre for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan

Abstract

Two new compounds, norkurchamide (3,20-dioxo-11α-hydroxycona-1,4-diene) (1) and pubatriol (3-oxo-11α,19,22-trihydroxycona-1,4-diene) (2) have been isolated from the bark of Holarrhena pubescens. Their structures have been established through spectroscopic studies.

■ Nortropane Alkaloids from the Leaves of Erythoxylum moonii

Khanzadi Fatima Khattak,* Atta-ur-Rahman, and M. Iqbal Choudhary

*International Centre for Chemical Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan

Abstract

Four new nortropane alkaloids have been isolated from the leaves of Erythroxylum moonii and identified as nortropane-3α-6β-7β-triol 3-benzoate 7- (2′-hydroxy-3′-phenylpropanoate) (1), nortropane-3α-7β-diol 7-trans- cinnnamate 3-propanoate (2), nortropane-3α-7β-diol 7-benzoate 3-(2′- methylpropanoate) (3), and nortropane-3α-7β-diol 3-(2′-methylpropanoate) 7-cis- (3′′,4′′,5′′-trimethoxycinnamate) (4). Additionally, five known bases are characterized as tropane-3α-7β-diol 7-benzoate (5), tropane-3α-7β-diol 3-phenylacetate (6), tropane-3α-7β-diol 3-benzoate (7), tropane-3α-6β-7β-triol 3-benzoate (8), and tropane-3α-yl 3-(3′,4′,5′-trimethoxybenzoate) (9). The structures for the compounds are proposed on the basis of spectroscopic evidences.

■ Pyrido[3,4-b]pyrazines. A New Application of 2-Chloro-3,4-diaminopyridine

Werner W. K. R. Mederski,* Dieter Kux, Markus Knoth, and Markus J. Schwarzkopf-Hofmann

*Merck KGaA, Preclinical Pharmaceutical Research, Frankfurter Str. 250, 64271 Darmstadt, Germany

Abstract

5-Chloropyrido[3,4-b]pyrazines were prepared from 1,2-dicarbonyl compounds and 2-chloro-3,4-diaminopyridine. Condensation of unsymmetrical glyoxals provided a mixture of two regiosiomers with 2-substituted pyrido[3,4-b]pyrazines as the major product. The regiochemistry was unambiguously assigned by 2D-NMR experiments. C-C- and C-N coupling reactions of 5-chloro or 5-oxo intermediates afforded the corresponding C-5 or N-6 substituted derivatives.

■ Ent-Kaurane Diterpenoids from Isodon rubescens var. lushiensis

Quanbin Han, Shenghong Li, Liyan Peng, and Handong Sun*

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

Abstract

Three new 6,7-seco-6,19:6,20-diepoxy-1α,7-olide-ent-kaurane diterpenoids, ludongnins C-E (1-3), along with six known analogs, macrocalyxoformins A (4) and B (5), sculponeatins A (6) and B (7), and ludongnins A (8) and B (9), were isolated from Isodon rubescens var. lushiensis. The structures of the new compounds were determined on the basis of the spectroscopic evidences. Compound (5) exhibited significant inhibitory activities against the Bcap37 and K562 cell lines with IC₅₀ = 0.82 and 0.62 μg/mL, respectively.

■ Convenient Synthesis of Furopyranopyrandione Derivatives by the CAN-mediated Furan Ring Formation

Kazuhiro Kobayashi,* Katsunori Nagase, Osamu Morikawa, and Hisatoshi Konishi

*Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

4H,9H-Furo[3,2-c]pyrano[3,4-e]pyran-4,9-dione (8) and (10) and 4H,5H-furo[2,3-b]pyrano[3,4-e]pyran-4,5-dione derivatives (9) were prepared in one step by treating 4-hydroxy-2H,5H-pyrano[4,3-b]pyran-2,5-diones (6) and alkenes (7) (or phenylacetylene) in acetonitrile with 2 equivalents of cerium(IV) ammonium nitrate (CAN).

■ C-Alkylated Coumarin and Coumarin Glycoside from Daphne oleoides

Abdul Malik,* Muhammad Riaz, Erum Akbar, Muhammad Rafique, and Nighat Afza

*H. E. J. Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan

Abstract

New C-alkylated coumarin (1) and coumarin glucoside (2) have been isolated from the roots of Daphne oleoides. The structures of 1 and 2 were established through spectroscopic and chemical studies.

■ Improved Oxidation of Active Methyl Group of N-Heteroaromatic Compounds by Selenium Dioxide in the Presence of tert-Butyl Hydroperoxide

Yoshinobu Tagawa, Katsuya Yamashita, Yoshitaka Higuchi, and Yoshinobu Goto*

*Faculty of Pharmaceutical Sciences, Fukuoka University, Nakamura, Jonan-ku, Fukuoka, 814-0180, Japan

Abstract

The oxidation of active methyl group of N-heteroaromatic compounds including both of bicyclic and monocyclic compounds using SeO₂ was considerably improved in the presence of tert-butyl hydroperoxde in dioxane to give the corresponding aldehyde or carboxylic acid in the moderate to good yields. The present oxidation proceeds more mildly and more selectively to form aldehyde rather than carboxylic acid, compared with conventional SeO₂ oxidation without tert-butyl hydroperoxide.

■ 3-Phenyl-l-menthopyrazole [(4R,7S)-7-isopropyl-4-methyl-3-phenyl-4,5,6,7-tetrahydroindazole]: A New Type of Chiral Auxiliary

Choji Kashima

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

Abstract

The preparation and the utility of 3-phenyl-l-menthopyrazole [(4R,7S)-7-isopropyl-4-methyl-3-phenyl-4,5,6,7-tetrahydroindazole] as a new type of chiral auxiliary are outlined.