HETEROCYCLES

■ Contents

■ Synthetic Routes towards Benzofuro[2,3-b]pyrroles and Benzofuro[2,3-b]indoles

Yuta Ito, Masafumi Ueda,* and Okiko Miyata*

*Department of Medicinal Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyamakitamachi, Higashinada, Kobe 658-8558, Japan

Abstract

This review provides a summary of the synthetic methods currently available for the construction of benzofuro[2,3-b]pyrroles and benzofuro[2,3-b]indoles. The latter of these two scaffolds features as a key structural element in characteristic bioactive natural products.

■ N-Ylides of 1,2,3-Triazoles and Tetrazoles – An Overview

Dietrich Moderhack*

*Institute of Medicinal and Pharmaceutical Chemistry, Technical University, Braunschweig, Beethovenstrasse 55, D-38106, Germany

Abstract

This treatise surveys the preparative chemistry of the title ylides as it developed from the beginnings in the early 1980s.

■ Efficient Installation and Elaboration of C4-C6 fused Furan Moiety in the Total Synthesis of Teucrium Clerodane Diterpenoids

Yen-Ku Wu, I-Chia Chen, Jia-Liang Zhu,* and Hsing-Jang Liu*

*Department of Chemistry, National Dong Hwa University, 1, Sec. 2, Hsueh Rd., Shou-Feng, Hualien 974, Taiwan, R.O.C.

Abstract

We previously reported the total synthesis of several Teucrium clerodane diterpenoids including teucvin (1), 12-epi-teucvin (2), montanin A (3) and teuscorolide (4) in a unified Diels-Alder approach. A full account for the tactical installation of the C4-C6 furan ring of 3 from an α,β-unsaturated lactone moiety, and the elaboration of the resulting furan unit into an α,β-unsaturated γ-hydroxyl lactone for preparing 4 is discussed herein. In addition, the transformation of 3 and its 12-epimer into 1 and 2 by the air-mediated furan oxidation reaction is described.

■ Hypervalent Iodine Mediated One-Pot C-H Functionalization at 2α- or 3α-Position of Indole Derivatives

Kazuhiro Higuchi,* Masato Inaba, Asuka Naganuma, Takako Ishizaki, Masanori Tayu, and Tomomi Kawasaki*

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

Abstract

The one-pot 2α- and 3α-functionalization of 2,3-disubstituted indoles using a hypervalent iodine reagent has been developed. The substitution at the 2α-position of indoles took place using phenyliodinebis(trifluoroacetate) with oxygen and carbon nucleophiles in moderate yields. The combination of iodosobenzene and trimethylsilyl azide afforded 3α-azide derivatives preferentially. The latter reaction was applied to other 2,3-disubstituted indoles.

■ One-Pot Preparation of 2-Arylbenzofurans from Oximes with Diaryliodonium Triflate

Kotaro Miyagi, Katsuhiko Moriyama, and Hideo Togo*

*Graduate School of Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

A variety of 2-arylbenzofurans were obtained in good yields by the O-arylation of oximes with diaryliodonium triflates, followed by the treatment with HCl in dioxane under warming conditions through the [3,3]-sigmatropic reaction. The present reaction is one-pot transition metal-free method for the preparation of various 2-arylbenzofurans from oximes, which are easily available from the reaction of alkyl aryl ketones with hydroxylamine.

■ Green Synthesis of 5-Substituted-1H-1,2,3,4-tetrazoles and 1-Sustituted-1H-1,2,3,4-tetrazoles via [3+2] Cycloaddition by Reusable Immobilized AlCl3 on γ-Al2O3

Hemmaragala Marishetty Nanjundaswamy* and Heidi Abrahamse

*Laser Research, Faculty of Health Sciences, University of Johannesburg, John Orr Building, Doornfontein Campus, 2028, South Africa

Abstract

We report the effectiveness of the surface modified γ-Al2O3 which is reusable, efficient, catalytic, safe and environmentally acceptable procedure for the conversion of both alkyl and aryl nitriles into the corresponding 5-substituted-1H-1,2,3,4-tetrazoles via [3+2] cycloaddition with sodium azide in excellent yields at mild reaction conditions (50 °C). The catalyst also afforded 1-substituted-1H-1,2,3,4-tetrazoles by the reaction of amines, sodium azide and triethyl orthoformate. The catalyst could be recycled and was reused eleven runs without losing its activity.

■ Synthesis of Heterocycles via Palladium-Catalyzed C-H Activation/Cyclization of Diazonium Salts (Part III): Phenanthridin-6-(5H)-ones

Pan Han, Jing Zhou, Cong-Cong Zhang, Ke Chen, and Zhen-Ting Du*

*College of Science, Northwest A＆F University, Yangling 712100, Shaanxi Province, China

Abstract

A series of phenanthridin-6-(5H)-ones were synthesized through a palladium-catalyzed C-H activation/cyclization strategy using diazonium salts in good yields. The best conditions included Pd(OAc)2 as the catalyst, PPh3 as the ligand, toluene as the solvent, K2CO3 as the base and 60 oC as the optimal temperature.

■ Microwave-Aided One-Pot Dehydration of the Alcohol Derived from (−)-Shikimic Acid for Efficient Synthesis of Pericosines

Koji Mizuki, Yusuke Yoneshige, Rikiya Kawahata, Hiroki Yoneyama, Shinya Harusawa, and Yoshihide Usami*

*Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

Dehydrating conditions of shikimate-derived alcohol 7, an early intermediate in the synthesis of the pericosine family of marine natural products, were examined. The triflate 8 was effectively converted to cyclohexadiene 9 with excess 4-N,N-dimethylaminopyridine (DMAP) at room temperature for 24 h. The reaction time was dramatically shortened by heating under microwave (MW) irradiation, preventing formation of the Diels–Alder type byproduct 14. Furthermore, the MW-aided one-pot dehydration of alcohol 7 with Tf2O and DMAP (2.4 eq.) to form diene 9 was realized.

■ A Simple Synthesis of 4-Hydroxy-3,4-dihydropyrido[3,4-d]pyrimidine-2(1H)-thione Derivatives by the Reaction of 3-Isothiocyanatopyridin-4-yl Ketones with Primary Amines

Kazuhiro Kobayashi,* Hiroki Inouchi, and Manami Konishi

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

Abstract

The reaction of aryl(3-isothiocyanatopyridin-4-yl)methanones, prepared easily from commercially available 3-aminopyridine, with primary amines at room temperature afforded 3-substituted 4-aryl-4-hydroxy-3,4-dihydropyrido[3,4-d]pyrimidine-2(1H)-thiones in good yields. These ketones could be converted to new tricyclic heterocyclic systems, 2,3-dihydro-5H-pyrido[3,4-d]thiazolo[3,2-a]pyrimidine and 3,4-dihydro-2H,6H-pyrido[3’,4’:4,5]pyrimido[2,1-b][1,3]thiazine, upon treatment with 2-bromoethanamine hydrobromide and 3-bromopropaneamine hydrobromide, respectively, in the presence two equivalents of triethylamine.

■ Phenyl Derivated Butyrolactones from the Fermentation Products of an Endophytic Fungus Aspergillus terreus

Yan-Qing Ye, Cong-Fang Xia, Juan-Xia Yang, Yu-Chun Yang, Xue-Mei Gao, Gang Du, Hai-Ying Yang, Xue-Mei Li,* and Qiu-Fen Hu*

*Key Laboratory of Ethnic Medicine Resource Chemistry, State Ethnic Affairs Commission & Ministry of Education, School of Chemistry and Biotechnology, Yunnan University of Nationalities, Kunming, Jingming South Road, Chenggong New District, Kunming, Yunnan 650500, China

Abstract

Two new phenyl derivated butyrolactones, terrephenols A and B (1 and 2), together with four known butyrolactones (3-6) were isolated from the fermentation products of a fungus Aspergillus terreus. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D- NMR techniques. The anti-tobacco mosaic virus (anti-TMV) activities of 1-6 were evaluated. Compounds 1 and 2 showed high anti-TMV activities with inhibition rates of 35.2% and 31.0 %, and 3-6 showed modest anti-TMV activity with inhibition rates of 15.4-24.6%, respectively. Compounds 1 and 2 were also tested for their cytotoxicities. 1 showed high cytotoxicity against A549 and MCF7 cell with IC50 values of 4.2 and 3.6 μM, and 2 showed high cytotoxicity against A549 and MCF7 cell with IC50 values of 3.9 and 4.8 μM, respectively.