HETEROCYCLES

■ Contents

■ Metal-Catalyzed Heterocyclization: Formation of Five- and Six-Membered Oxygen Heterocycles through Carbon-Oxygen Bond Forming Reactions

Krishna C. Majumdar,* Pradip Debnath, and Brindaban Roy

*Department of Chemistry, University of Kalyani, Kalyani 741 235, West Bengal, India

Abstract

This review describes the synthesis of five- and six-membered oxygen heterocycles through carbon-oxygen bond formation by metal catalyzed heterocyclization published during 2005 to 2008.

■ A Three-Dimensionally Oriented π-Conjugated System: Synthesis of the Porphyrins Bearing Terthiophene Pendant Strands

Toru Amaya, Koichi Mori, and Toshikazu Hirao*

*Department of Applied Chemistry, Graduate School of Science, Osaka University, 2-1 Yamadaoka, Suita, Osaka 560-0871, Japan

Abstract

The porphyrins bearing three-dimensionally oriented terthiophene pendant strands were synthesized to elucidate the conformational behaviour.

■ Chemistry of Heteroaryltriphenylphosphonium Iodides: Preparation from Iodoheteroaromatics and Elimination of the Phosphonium Iodide Group Using Basic Solvents

Akihiro Sato, Osamu Sugimoto,* and Ken-ichi Tanji*

*Laboratory of Organic Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan

Abstract

α- and γ-Iodoheteroaromatics were found to react with triphenylphosphine to give heteroaromatictriphenylphosphonium iodides in excellent yields. β-Iodoheteroaromatics, which are less reactive with triphenylphosphine compared to α- or γ-compounds, were converted into the corresponding phosphonium iodides using palladium catalysts. Treatment of heteroaryltriphenylphosphonium iodides resulted in the elimination of the phosphonium iodide group using basic solvents such as aqueous sodium hydroxide or ethanol - triethylamine.

■ A Novel Molecular Cleft Based on Dioxocin Ring, Part I: Synthesis and Conformational Analysis

Bahareh Vafakish and Parviz Rashidi-Ranjbar*

*School of Chemistry, College of Science, University of Tehran, Tehran 14155-6455, Iran

Abstract

The Molecular cleft 1 using 8-methyl-16H-dinaphtho[2,1-d:1,2-g][1,3]dioxocin-2,14-diol as a spacer was synthesized. Density functional calculations at B3LYP/6-31G level of theory indicates that 8-methyl-16H-dinaphtho[2,1-d:1,2-g][1,3]dioxocin, the central part of 1, could be populated in two stable conformations, i.e. BC and DB with difference in total energy of 0.12 kcal/mol. 1H-NMR spectroscopy, based on geminal coupling constants, shows that DB form is the most populated conformation of 1 in solution.

■ The Synthesis, Structure and Reactivity of 1-Thioxotetrahydropyridazino[1,2-a][1,2,4]triazin-4(1H)-one

Sandra Jarrett,* Ainka Brown, and Marvadeen Singh-Wilmot

*Department of Chemistry, Mona Campus, University of the West Indies, Mona, Kingston 7, Jamaica

Abstract

The synthesis of 1-thioxotetrahydropyridazino[1,2-a][1,2,4]triazin-4-(1H)-one 3 in five steps from tert-butyl carbazate and its transformation into 3-benzylidene and 1-amino derivatives are described. Its crystal structure is presented showing it to be an axially chiral molecule that exists as a racemate in the solid state.

■ Reactions of 2-(Lithiomethyl)phenyl Isocyanides with Methyl 1-Methylindole-3-carboxylate: Flaborations of the Adducts to 5H-Benz[2,3]azepino[5,6-c]indol-12-one and 2,3’-Biindolyl Derivatives

Kazuhiro Kobayashi,* Daisuke Nakai, Shuhei Fukamachi, and Hisatoshi Konishi

*Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

It has been found that when 2-(lithiomethyl)phenyl isocyanides were allowed to react with methyl 1-methylindole-3-carboxylate, the corresponding 1,4- and/or 1,2-adducts were obtained. The 1,4-adducts could be transformed into 6,11-dihydro-5H-benz[2,3]azepino[5,6-b]indol-12-ones derivatives by acid hydrolysis, followed by lactamization and subsequent dehydrogenation. The transformation of the 1,2-adducts into 2,3’-biindolyls was accomplished by a sequential treatment with hydrochloric acid and aqueous sodium hydroxide.

■ Formation Pathway of Novel Cycloadduct Obtained by Reaction of 3,5-Disubstituted 4-Oxo-4H-pyrazole 1,2-Dioxide with Dimethyl Acetylenedicarboxylate

Yasuyuki Yoshitake, Koki Yamaguchi, and Kazunobu Harano*

*Laboratory of Molecular Design, Sojo University, 4-22-1, Ikeda, Kumamoto-shi, 860-0082, Japan

Abstract

A new formation pathway via [3,3]-sigmatropic rearrangement of the 1,3-dipolar reaction product was proposed for the novel nitrogen-free compound formed from the reaction of 3,5-disubstituted 4-oxo-4H-pyrazole 1,2-dioxide with dimethyl acetylenedicarboxylate.

■ A Convenient Synthesis of Novel Spiroisoindole γ-Halobutyrolactones via Halocyclization of γ-Ethylenic Acids

Mohamed M. Rammah, Mohamed Othman,* Kabula Ciamala, Michael Knorr, Carsten Strohmann, and Mohamed B. Rammah

*Laboratory of Organic Chemistry, URCOM, EA 3221, Faculty of Sciences and Techniques, University of Le Havre, 25 Rue Philippe Lebon, BP 540, F-76058 Le Havre Cedex, France

Abstract

γ-Ethylenic carboxylic acids are cyclized to spiroisoindolone γ-halomethylbutyrolactones, in the presence of NBS or NIS and K2CO3. The corresponding haloaspirobutyrolactones were isolated in high yields (57-95%).

■ Diels-Alder Reactions between Acrolein N,N-Dimethylhydrazone and N-Benzylated Benzotriazole-, Indazole- or Indole-4,7-diones

Christelle Marminon,* Bernard Fenet, Valeria Mignosi, Raphael Terreux, and Pascal Nebois

*INSERM U 863, Laboratory of Organic Chemsitry , University of Lyon 1, ISPB, 8 avenue Rockefeller, 69373 Lyon cedex 08, France

Abstract

Diels-Alder reactions between acrolein N,N-dimethylhydrazone 4 and N-benzylated benzotriazole, indazole and indole-4,7-diones 1, 2 and 3 afforded new heterotricyclic quinones 5, 7 and 9 including from 2 to 4 intracyclic nitrogen atoms. A structural assignment of all new compounds was achieved using 2D NMR 1H-13C HMBC correlations. The single 1,8- regioisomer was isolated starting from benzotriazole or indazole quinones, while a mixture of the 1,5- and 1,8- regioisomers was obtained from an indole-4,7-dione derivative. In all cases, the observed regiochemistry was in agreement with FMO calculation.

■ Synthesis of Heteroaryl-fused Pyrazoles as P38 Kinase Inhibitors

Sarah C. Abbot, Roland J. Billedeau, Nolan J. Dewdney, Tobias Gabriel, David M. Goldstein, Kristen L. McCaleb,* Michael Soth, Teresa Alejandra Trejo-Martin, and Hasim Zecic

*Department of Medicinal Chemistry, Roche Paolo Alto LLC, 3401 Hillview Avenue, Palo Alto, CA 94304, U.S.A.

Abstract

The synthesis of pyrazolo-pyridine, pyrimidine, pyrazine and pyridazine heterocycles is described. In addition, we report the utilization of 2,4-difluorophenoxide as a leaving group, to facilitate formation of the desired pyrazole adducts.

■ Two New Sesquiterpene Glucosides from Gymnaster koraiensis

Il Kyun Lee, Ki Hyun Kim, Shi Yong Ryu, and Kang Ro Lee*

*Natural Products Laboratory, College of Pharmacy, Sungkyunkwan University, 300 Chunchun-dong, Jangan-ku, Wuwon 440-746, Korea

Abstract

Two new sesquiterpene glucosides, 1(R),4β-dihydroxy-trans-eudesm-6-ene-1-O-β-D-glucopyranoside (1) and 1(R),4β-dihydroxy-trans-eudesm-7-ene-1-O-β-D-glucopyranoside (2), together with six other known compounds, were isolated from the flowers of Gymnaster koraiensis (Nakai) Kitamura (Compositae). The identification and structural elucidation of these compounds were based on 1D- and 2D-NMR spectral data analysis. The absolute configurations of 1 and 2 were determined by a convenient Mosher ester procedure carried out in NMR tube.

■ Thieno[2,3-f]triazolo[1,5-a][1,4]diazepines and Thieno[2,3-f]triazolo[1,5-a][1,4]oxazepines from Azide Cycloaddition

Giorgio Molteni* and Paola Del Buttero

*Department of Organic and Industrial Chemistry, University of Milano, Via Golgi 19, 20133 Milano, Italy

Abstract

Intermolecular dipolar cycloadditions between 2-methoxycarbonyl- 3-thenylazide (3) and monosubstituted dipolarophiles bearing a triple carbon-carbon bond were exploited in a three step synthesis of the title compounds. The intramolecular cycloaddition of substituted thenylazide (11) was also carried out in the two-step synthesis of the thieno[2,3-f][1,2,3]triazolo[1,5-a][1,4]diazepine derivative (8).

■ Decarboxylative Bromination of Indole-2,3-dicarboxylic Acids Using Oxone® or CAN in the Presence of Lithium Bromide

Hideaki Umemoto, Misako Umemoto, Chiaki Ohta, Masashi Dohshita, Hiroki Tanaka, Syo Hattori, Hiromi Hamamoto, and Yasuyoshi Miki*

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

Abstract

The treatment of 1-methylindole-2,3-dicarboxylic acid with Oxone® and lithium bromide produced 3,3-dibromo-1-methyloxindole. However, the reaction of 1-benzenesulfonylindole-2,3-dicarboxylic acid with Oxone® and lithium bromide afforded 1-benzenesulfonyl-2,3-dibromoindole. In a similar manner, 2,3,5,6-tetrabromoindole was synthesized from 1-benzenesulfonyl-5,6-dibromoindole-2,3-dicarboxylic acid.

■ Regioselective Nitroalkylation of the 1-Methyl-2-quinolone Framework

Motoki Asahara, Masaki Ohtsutsumi, Masahiro Ariga, and Nagatoshi Nishiwaki*

*School of Science and Technology, Kochi University of Technology, Tosayamada-cho, Kochi, 782-8502, Japan

Abstract

Regioselective introduction of an (α-nitro)alkyl group to the 1-methyl-2-quinolone framework was performed upon treatment of 1-methyl-3,6,8-trinitro-2-quinolone with nitroalkanes in the presence of triethylamine, in which a nitronate anion attacks at the 4-position and the subsequent aromatization by elimination of nitrous acid lead to 4-(α-nitro)alkylated 6,8-dinitro-1-methyl-2-quinolones.

■ 13-Bromomonocillin I: A New WNT-5A Expression Inhibitor Produced by Pochonia chlamydosporia var. chlamydosporia

Hideki Shinonaga,* Noriyoshi Sakai, Yuriko Nozawa, Akiko Ikeda, Mari Aoki, and Akira Kawashima

*Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-Cho, Kita-ku, Saitama-city, Saitama 331-9530, Japan

Abstract

WNT-5A is a secretory glycoprotein related to the proliferation of dermal papilla cells. While searching for an inhibitor of WNT-5A expression, a new compound, 13-bromomonocillin I (1), was isolated from the fermentation broth of the fungus Pochonia chlamydosporia, cultured in NaBr-supplemented medium. 13-Bromomonocillin I (1) exhibited WNT-5A expression inhibitory activity with an IC50 value of 0.25 μM.