HETEROCYCLES

■ Contents

■ Recent Development in Palladium-Mediated Synthesis of Nitrogen Heterocycles

Krishna C. Majumdar,* Buddhadeb Chattopadhyay, Pradip K. Maji, Sudip K. Chattopadhyay, and Srikanta Samanta

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

Abstract

This review describes the synthesis of nitrogen heterocycles by palladium-mediated cyclization. This report covers literature published during 2003 to 2007.

■ Synthesis of Bis-Aryl Phosphates Based on Triazine Scaffold

Caroline Courme, Nohad Gresh, Christine Lenoir, Michel Vidal, Christiane Garbay, Jean-Claude Florent, and Emmanuel Bertounesque*

*Medicinal Chemistry, C.N.R.S. UMR 176, 26 rue d’Ulm, Paris 75005, France

Abstract

In view of targeting the Grb2-SH2 signaling protein, the synthesis of potential ligands based on the 1,3,5-triazine scaffold bearing two phenylphosphate groups is described. The triazine functionality was introduced using an orthogonal strategy via the sulfone chemistry.

■ N-Protected N2-Ethoxymethylenephenylglycine Hydrazides as Precursors of 1,3,4-Oxadiazole Derivatives

Agnieszka Kudelko* and Wojciech Zieliński

*Department of Chemical Organic Technology and Petrochemistry, The Silesian University of Technology, Ul. Krzywoustego 4, PL-44100 Gliwice, Poland

Abstract

New derivatives of N2-ethoxymethylene phenylglycine hydrazide protected at the amino group by acetyl and tert-butoxycarbonyl were synthesized with reactions of N-protected phenylglycine hydrazides and triethyl orthoesters. They underwent cyclization to the corresponding N-protected 2-aminomethyl-1,3,4-oxadiazoles in the presence of glacial acetic acid.

■ Gymnastatins I-K, Cancer Cell Growth Inhibitors from a Sponge-Derived Gymnascella dankaliensis

Taro Amagata,* Keiko Takigawa, Katsuhiko Minoura, and Atsushi Numata*

*Department of Chemistry and Biochemistry, San Francisco State University, 1600 Holloway Ave., San Francisco, CA 94132, U.S.A.

Abstract

The Halichondria sponge-derived fungus, Gymnascella dankaliensis, was cultured in a malt extract medium containing the bromine source. Three new metabolites, gymnastatins I (5)–K (7), have been isolated from the mycelial MeOH extract. The spectroscopic analyses using 1D and 2D NMR techniques have established the stereostructures of 5–7 in which chlorine atoms in gymnastatins A (1)–C (3) are respectively replaced by bromine atoms. All of the isolated metabolites (5–7) exhibited growth inhibition against the P388 cancer cell line. Furthermore, gymnastatins I (5) and J (6) showed appreciable growth inhibition against the human cancer cell lines.

■ New Cyanoglycosides, Hydracyanosides D, E, and F, from the Leaves of Hydrangea macrophylla

Zhibin Wang, Seikou Nakamura, Hisashi Matsuda, Lijun Wu, and Masayuki Yoshikawa*

*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Abstract

Three new cyanoglycosides named hydracyanosides D (1), E (2), and F (3) were isolated from the leaves of Hydrangea macrophylla cultivated in China together with 17 known constituents including hydracyanoside A (4). Their structures were elucidated on the basis of chemical and physicochemical evidence.

■ Synthesis and Tuberculostatic Activity of Novel 1,2,4-Triazoles Obtained from Heterocyclic Carbohydrazides

Katarzyna Gobis,* Henryk Foks, Zofia Zwolska, and Ewa Augustynowicz-Kopeć

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

Abstract

The novel 1,2,4-triazole derivatives have been synthesized by a few different pathways. Heterocyclic carbohydrazides were used to obtain monoesters of hydrazine acids (1-6), thiosemicarbazide derivatives (7-17), and finaly 1,2,4-triazole-5-thiones (18-38). Carbohydrazides were also cyclized with methyl carbamodithioates in the presence of DBU giving 1,2,4-triazole-5-thiones (18, 19, 39-47). Two of final products (39, 40) were undergone alkylation in alkaline solution to appropriate sulfides (48-53). Then methylsulfides (48, 49) were oxidized with peroxyacetic acid to sulfoxides (54, 55). The obtained compounds were tested in vitro towards Mycobacterium tuberculosis.

■ A Highly Effective One-Pot Synthesis of Quinolines from 2-Alkynylnitrobenzenes

Kentaro Okuma,* Saori Ozaki, Jun-ichi Seto, Noriyoshi Nagahora, and Kosei Shioji

*Department of Chemistry, Faculty of Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

A highly effective one-pot synthesis of poly-substituted quinolines from 2-alkynylnitrobenzenes using inexpensive reagents has been developed. Reaction of 2-alkynylnitrobenzenes with Sn/HCl in EtOH resulted in the formation of 2-aminophenyl ketones and subsequently condensed in situ with ketones to form tri-substituted quinolines in 80-97% yields.

■ The Synthesis of Some Benzimidazolium Salts and Use as Carbene Precursors in the Heck and Suzuki Reactions

Beyhan Yiğit, Murat Yiğit,* İsmail Özdemir, and Engin Çetinkaya

*Department of Chemistry, Faculty of Arts and Sciences, Adıyaman University, 20240 Adıyaman , Turkey

Abstract

Novel 1-(2-diisopropylaminoethyl)-3-alkylbenzimidazolium salts as N-heterocyclic carbene precursors 2a-g were prepared by quarternazition of 1-(2-diisopropylaminoethyl)benzimidazoles in DMF with alkyl halides. The salts were characterized spectroscopically and in situ formed complexes from Pd(OAc)2 and 2 have been tested as catalyst in homogenous Heck and Suzuki reactions.

■ A Short and Convenient Synthesis of Novel Thienopyrazolodiazepine and Thienopyrazoloxazepine Skeletons via Nitrilimine Cycloaddition

Giorgio Molteni* and Paola Del Buttero

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

Abstract

Silver carbonate treatment of 3-thenyl-substituted hydrazonoyl chloride (3) promoted the in situ generation of the corresponding nitrilimine (4) which constitute the key intermediate in the three step synthesis of both thieno[2,3-f]pyrazolo[1,5-a][1,4]diazepine and thieno[2,3-f]pyrazolo[1,5-a][1,4]oxazepine skeletons. The concurrent formation of unusual pyridazine derivatives arising from the electrophilic attack of a nitrilium cation to the carbon-carbon double bond is also discussed in some detail.

■ DDQ-Mediated Tandem Synthesis of Functionalized Pyranocoumarins from 4-Hydroxycoumarins and 1,3-Diarylallylic Compounds

Zhenxing He, Xufeng Lin,* Yuanxun Zhu, and Yanguang Wang

*Department of Chemistry, Zhejiang University , Hangzhou, 310027, China

Abstract

A simple and efficient DDQ-mediated oxidative cross-coupling between 4-hydroxycoumarin and 1,3-diarylallylic compounds was developed. The reaction furnished functionalized pyranocoumarins in a single step without using any metal catalyst. The tandem process involves an intermolecular C–C bond formation and an intramolecular C–O bond formation through double oxidative C–H activation.

■ A Novel Approach to Diindenocarbazoles via Palladium-Catalyzed Intramolecular Arylation

Lingling Rong, Qiancai Liu,* Jie Tang, and Zhenguo Chi

*Department of Chemistry, East China Normal University, 3663 Zhongshan RD(N9, Shanghai 200062, China

Abstract

The diindenocarbazole derivatives are synthesized by the reaction of 2,7-dibromo-9-hexylcarbazole with benzoyl chloride under Friedel-Crafts conditions, followed by Wolff-Kishner-Huang reduction to produce 3,6-dibenzyl-2,7-dibromo-9-hexylcarbazole, which was cyclized to form bis(indeno)-9-hexylcarbazole by palladium-catalyzed double intramolecular arylation. The diindeno-carbazole was further converted into fully alkylated compounds.

■ Peptide Mass Spectrometry by Ionic Probe Attachment Ionization Using NHS-TMpybox and Mal-TMpybox

Fumihiro Ito and Kentaro Yamaguchi*

*Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki City, Kagawa 769-2193, Japan

Abstract

The application of a new ionization method that uses metal-complex-based ionization probes containing the 2,6-bis(oxazolinyl)pyridine (pybox) ligand for bioactive peptides is presented. Bradykinin, angiotensin-I, angiotensin-II, and nociceptine as well as a couple of pentapeptides were analyzed. This method was proven to effectively ionize large complex molecules, including biomolecules.

■ 12-epi-Fragilide G, a New Briarane-Type Diterpenoid from the Gorgonian Coral Ellisella robusta

Yu-Chia Chang, Tsong-Long Hwang, Sheng-Kai Huang, Li-Won Huang, Mei-Ru Lin, and Ping-Jyun Sung*

* , National Museum of Marine Biology and Aquarium, 2 Houwan Road, Checheng, Pingtung, Taiwan 944, Taiwan, R.O.C.

Abstract

A new chlorinated briarane-type diterpenoid, 12-epi-fragilide G (1), was isolated from the gorgonian coral Ellisella robusta. The structure of 1 was elucidated by the interpretations of spectral data analysis and this compound was found to possess an s-cis diene moiety in its structure. Briarane 1 displayed inhibitory effects on elastase release by human neutrophils.

■ Photoinduced Electron Transfer-Initiated Selective Cyclization Reactions of (Z)-N-Benzoyl-α-dehydro(1-naphthyl)alaninamides into 4,5-Dihydrooxazole Derivatives

Yuhki Sato, Atsuhiko Yoshida, Tetsutaro Igarashi, and Tadamitsu Sakurai*

*Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

An investigation was undertaken to gain understanding of substituent and solvent effects on the photoreactivity of the title 1-naphthylalanine N’,N’-disubstituted amides [(Z)-1] and the (Z)-1-derived product composition. Results indicated that the photoinduced electron transfer reaction of (Z)-1 in methanol containing triethylamine (TEA) proceeds less efficiently than that of the corresponding 1-naphthylalanine alkyl esters to afford cis-4,5-dihydrooxazoles in preference to the trans-isomers and also the former isomers undergo negligible isomerization to the latter isomers in the presence of TEA. Analysis of solvent effects substantiated that both the polarity of solvent and the ability of solvent to donate proton or to accept electron are major factors for controlling the photoreactivity and product composition ratio.