HETEROCYCLES

■ Contents

■ Synthetic Approaches for Heteroannulated Chromones Fused Various Heterocyclic Systems

Salsabeel H. Hashiem, Magdy A. Ibrahim, Al-Shimaa Badran,* Nasser M. El-Gohary, and Hassan A. Allimony

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy 11711, Cairo, Egypt

Abstract

The main focus of this review summarized the different methods utilized for the synthesis of chromone annulated with different heterocyclic rings such as pyrroles, furans, pyrazole, imidazole, benzene, naphthalene, quinolone……and others.

■ Systematic Search for Transition States in Complex Molecules: Computational Analyses of Regio- and Stereoselective Interflavan Bond Formation in Flavan-3-ols

Daisuke Urabe* and Keisuke Fukaya

*Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan

Abstract

This review describes our recent work on a systematic search for transition states in transformations of complex molecules. The method features a combination of a conformational search method using constrained models to create a large library of transition-state candidates, and subsequent density functional theory (DTF)-based transition state calculations for the candidates. The method is applicable to calculation of transition states for inter- and intramolecular interflavan bond formation in flavan-3-ols to reproduce experimental results for highly regio- and stereoselective C-C bond formation. The specific roles of van der Waals interactions in the transition states can be visualized by NCIPLOT mapping to show the importance of weak but attractive interactions for selective interflavan bond formation.

■ Acylative Desymmetrization of Glycerol Derivatives by Chiral DMAP Derivatives

Hiroki Mandai,* Kosuke Ashihara, Koichi Mitsudo, and Seiji Suga*

*Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science, 4-3-3 Nijigaoka, Kani, Gifu, 509-0293

Abstract

An efficient enantioselective acylative desymmetrization of glycerol was developed by using a chiral DMAP derivatives 1e having a 1,1ʹ-binaphthyl unit. The reactions required only 0.1 mol% of the catalyst and showed moderate to good enantioselectivity (up to 94:6 er). Control experiments revealed that the first acylation of a glycerol derivative proceeded selectively rather than the second acylation to give diacylate.

■ Facile Preparation of 2-Aryl-3-iodopyrroles with N-Tosyl 4-Aryl-3-butyn-1-ylamines, I2, and tBuOK

Kaho Shibasaki, Hiroki Naruto, and Hideo Togo*

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

Abstract

Treatment of N-tosyl 4-aryl-3-butyn-1-ylamines with I2 and K2CO3, followed by the reaction with tBuOK under mild conditions gave 2-aryl-3-iodopyrroles in good yields. The present approach is a one-pot method for the preparation of 2-aryl-3-iodopyrroles from N-tosyl 4-aryl-3-butyn-1-ylamines, which could be easily prepared from aryl iodides, N-(3-butyn-1-yl)phthalimides, and p-toluenesulfonyl chloride.

■ Synthesis and Biological Activities of Some New Phosphorus Compounds Containing Pyranopyrazole Moiety

Tarik E. Ali,* Mohammed A. Assiri, Hafez M. El-Shaaer, Somaia M. Abed-Kariem, Wafaa R. Abdel-Monem, Somaya M. El-Edfawy, Noha M. Hassanin, Ali A. Shati, Mohammad Y. Alfaifi, and Serag Eldin I. Elbehairi

*Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia.

Abstract

A simple method for construction of functionalized pyranopyrazoles containing phosphoramide and phosphonate groups via one-pot reaction was achieved. The methodology depended on the reaction of 6-amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (3) with triethyl phosphite and hexaethylphosphoramide and so with diethyl phosphite in the presence of chloroacetyl chloride or carbon disulfide. The products were screened for their antimicrobial, antioxidant and antiproliferative properties. Compound 7 displayed promising antimicrobial and antioxidative properties. Also, compound 8 showed potent cytotoxic effects against MCF-7, HepG-2 and HCT-116 cancer cells with IC50 values in range 5.3 ± 0.9 to 7.5 ± 0.6 μg/mL. Acridine orange and ethidium bromide were used for the detection of viable, apoptotic, and necrotic cells. The early apoptotic cell death was observed by the compounds in all types of the treated cells. Compounds 5, 7 and 8 induced high percentage of necrosis towards all treated cells. The late apoptosis was recorded as a high rate after treatment with compound 3 in HepG-2 cells.

■ Metal-Free sp3 C-H Bond Oxidation and Functionalization of α-Bromoketones to Quinoxalinone, Benzoxazinone, and Benzothiazinone Heterocyclic Compounds

Tianlong Wei, Haiying Tian, Fang Guo,* Hongxue Qi, and Xiuling Chen*

*School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, China

Abstract

A series of heterocyclic compounds (benzothiazinones, benzoxazinones and quinoxalinones) were efficiently synthesized in excellent yields via α-bromoketones with o-substituted aniline (2-aminothiophenol, aryl-1,2-diamines and 2-aminophenol). This protocol accomplishes sp3 C-H bond oxidation and functionalization in one-pot without any metal catalyst.

■ Three-Component Reaction of Arynes, Quinolines, and Chloroform: Two-Step Synthesis of 2-Quinolinones from Quinolines

Kentaro Okuma,* Shiho Inomata, Yuxuan Qu, and Noriyoshi Nagahora

*Faculty of Science, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

Reaction of quinoline with benzyne prepared from benzenediazonium-2-carboxylate and chloroform gave 1-phenyl-2-trichloromethyl-1,2-dihydroquinoline in 79% yield. Basic hydrolysis of dihydroquinoline by KOH resulted in the formation of 2-quinolinone in 85% yield.

■ An Efficient SeO2/FeCl3 Promoted Acylation:Intramolecular Friedel-Crafts Reaction Leading to a One-Pot Synthesis of Wrightiadione and Its Derivatives

Huan Zhang, Qi Wang, Lu Huang, Ziye Tian, Shunguang Zhang,* and Youlai Zhang*

*Tianjin Key Laboratory of Drug Targeting and Bioimaging, School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, P.R. China.

Abstract

Wrightiadione has been shown to exhibit a broad range of biological activities. An efficient and straightforward synthetic method for generating wrightiadione and its derivatives which contain a unique tetracyclic isoflavone moiety was developed. This unprecedented one-pot route utilizes a wide spread of substrates through three-step tandem Riley oxidation/Friedel-Crafts reaction/oxidation with SeO2/FeCl3 in moderate yield.

■ Anti-Tobacco Mosaic Virus Isoindolin-1-ones from the Stems of Nicotiana tabacum

Jian-Duo Zhang, Xin Liu, Li Xu, Jia-Rui Jiang, Le-Le Deng, Wen-Wu Yang, Xue-Mei Li, Guang-Yu Yang, Tao Zhou,* and Feng-Xian Yang*

*Technology Center, China Tobacco Yunnan Industrial Co., Ltd., Kunming, Yunnan 650231, China

Abstract

Three new (1-3) and three known (4-6) isoindolin-1-ones were isolated from the stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-3 were tested for their anti-tobacco mosaic virus (anti-TMV) activitiy. The results showed that compounds 1-3 showed high anti-TMV activity with inhibition rates of 42.6, 46.7 and 38.5% at the concentration of 20 μM, respectively. These rates are higher than that of ningnanmycin, a positive control.

■ Recyclable Heterogeneous Nanocrystal Promoted Cascade Reaction in Water: An Access to Green Synthesis of Highly Functionalized 4H-Pyrans Containing Phosphonate Motif

Yong-Hong Cai, Ya-Sa Xie, Ran Li, Ming-Mei Fan, Jing-Jing Li, Chuan-Bao Zhang,* and Jin-Fang Yuan*

*College of Chemistry and Chemical Engineering, Henan University, Kaifeng, 475004, China.

Abstract

A green and environmentally friendly cascade reaction of diethyl (2-phenylacetyl)phosphonate with benzylidenemalononitrile promoted by Zr-Ce-SBA-15-NH2 in water was developed, and a wide range of highly functionalized 4H-pyrans containing phosphonate motif were obtained in up to 89% yield. Moreover, SBA-15-NH2 also showed good catalytic activity for this transformation in acetonitrile.

■ Facile Access to Highly-Substituted Dihydrofurans Using Resonated Vinylpentanedione Radicals Generated by Mn(III)-Based Oxidation

Sousuke Oka, Shintaro Hashimoto, Kazuki Hisano, and Hiroshi Nishino*

*Department of Chemistry, Graduate School of Science, Kumamoto University, Kurokami 2-39-1, Chûou-Ku, Kumamoto 860-8555

Abstract

Useful and easy access to highly-substituted dihydrofurans, which convert into various acetals, was established using the common Mn(III) oxidation. The key point is to use resonated vinylpentanedione radicals that cyclize to produce the desired acetoxydihydrofurans which are transformed into the hemiacetals and acetals in good yields under very mild conditions.

■ A One-Pot Approach to Construct 3-(2-Methoxypyridin-3-yl)-4H-chromen-4-ones via Meinwald Rearrangement/Intramolecular Demethylation Annulation of Epoxides

Min-Qi Hu, Ying Zhang, Kai-Li Dai, Li-Fang Yu, Ting Liu, Jie Tang, and Fan Yang*

*Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, PR China

Abstract

A convenient and practical approach for construction of 3-(2-methoxypyridin-3-yl)-4H-chromen-4-ones has been successfully developed by a one-pot Meinwald rearrangement/intramolecular demethylation annulation reaction sequence with easily accessible epoxides as the starting material. The synthetic protocol is of excellent functional group compatibility under mild reaction conditions, and 3-(2-methoxypyridin-3-yl)-4H-chromen-4-ones were obtained in high yields. Moreover, further derivation successfully furnished more complicated derivatives by Suzuki-Miyaura cross-coupling reaction which may provide a promising potential application in exploring biological activity of 3-aryl-4H-chromen-4-ones.