HETEROCYCLES

■ Contents

■ 5,15-Diheteroporphyrins Synthesized from α,α'-Dihalodipyrrin as a Key Building Block

Soji Shimizu*

*Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan

Abstract

A facile synthesis of meso-aryl-substituted α,α'-dihalodipyrrins and their use as starting materials in the porphyrin synthesis have enabled creation of various porphyrin analogues containing heteroatoms at two opposite meso-positions, namely 5,15-positions. Incorporation of lone pair electrons into the 18π-electron aromatic conjugated system of porphyrin allows the system to attain antiaromaticity with unique optical and electrochemical properties. This review summarizes the recent development in the chemistry of 5,15-diheteroporphyrins synthesized from meso-aryl-substituted α,α'-dihalodipyrrins.

■ Preparation and Acetylcholinesterase Inhibitory Activities of Pyridine-Based 1,3,4-Oxadiazole Derivatives

Xiang Yu,* Wude Yang, Ling Huang, Xingji Zhou, and Yafang Chen*

*Department of Pharmacy, Guizhou University of Traditional Chinese Medicne, , China

Abstract

Fourteen pyridine-based 1,3,4-oxadiazole derivatives were synthesized from pyridine-2-carboxaldehyde via iodine-mediated oxidative cyclisation with substituted hydrazide by using the impregnation method. Their structures were confirmed by melting point, 1H NMR, 13C NMR and HRMS. Preliminary bioassay of these derivatives' activities inhibiting acetylcholinesterase (AChE) was also evaluated in vitro at the concentration of 1 μmol/mL. The result showed that compounds 4c, 4j and 4k had moderate inhibitory activities with 52%, 59% and 59%, respectively. The preliminary structure-activity relationships revealed that the introduction of pyridine ring could enhance the activity. Molecular docking study demonstrated that compound 4k possessed an optimal docking pose with interactions at the middle of the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE.

■ Chemical Transformations with 4,9-Dimethoxy-5-oxo-5H- Furo[3,2-G]chromene-6-carbonitrile: Construction and Antimicrobial Evaluation of the Novel Heteroannulated Furochromenopyridines

Magdy A. Ibrahim,* Sami A. Al-Harbi, and Esam S. Allehyani

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

Abstract

The chemical reactivity of 4,9-dimethoxy-5-oxo-5H-furo[3,2-g]- chromene-6-carbonitrile (1) was studied towards a variety of active methylene nitriles namely; malononitrile, cyanoacetamide, N-phenylcyanoacetamide, (phenylthio)acetonitrile, ethyl cyanoacetate and benzothiazol-2-ylacetonitrile producing the novel annulated furo[3’,2’:6,7]chromeno[2,3-b]pyridines. Reactions of carbonitrile 1 with malononitrile dimer, cyanoacetohydrazide and 1H-benzimidazol-2-ylacetonitrile showed different behavior giving the novel angular heteroannulated furochromenes 10, 11 and 13, respectively. A series of novel furo[3’’,2’’:6’,7’]chromeno[3’,2’:5,6]pyrido[2,3-d]pyrimidines were also synthesized. The proposed mechanisms for the different synthetic pathways were also discussed. The prepared compounds were screened in vitro for their antimicrobial activity and some of them showed notable activity against the tested microorganisms. Structures of the synthesized products were confirmed based on their analytical and spectral data.

■ Synthesis of Dimethoxy Activated Benzimidazoles and Bisbenzimidazoles

Mahiuddin Alamgir, Glenn C. Condie, Vesna Martinovic, Joanne Wood, Hayat Sholihin, Paul K. Bowyer, Naresh Kumar, and David StC. Black*

*School of Chemistry, The University of New South Wales, Sydney 2052, Australia

Abstract

A range of 2-substituted-4,6-dimethoxy activated benzimidazoles and 2,2'-bisbenzimidazoles have been synthesized from 2-aminoanilide derivatives under acidic conditions. The starting materials were prepared either by acylation from 3,5-dimethoxyaniline followed by nitration, or by acylation from 3,5-dimethoxy-2-nitroaniline. The 2-nitroanilides were then reduced by palladium catalyzed reaction with hydrazine and subsequent acid catalyzed cyclization giving the corresponding 4,6-dimethoxybenzimidazoles and 4,6-dimethoxy-2,2'-bisbenzimidazoles. In addition, 2-phenyl-4,5,6-trimethoxybenzimidazole has been synthesized using a similar procedure.

■ Efficient Synthesis of 2-Functionalized Benzoxazoles Catalyzed by Copper Iodide

Han Cao,* Xue-Jing Liu,* Fu-sheng Bie, Peng Yan, Jie Ma, Yi-jun Shi, and Ying Han

*Engineering and Technology Research Institute of Lunan Coal Chemical,, Zaozhuang University, 1 Beian Road, China

Abstract

We reported an efficient synthesis of 2-functionalized benzoxazoles in mild condition and excellent yields. The synthetic process includes two steps. The step one contains a reaction of pendent halide formamidine derivatives and 2- aryloxyacetyl chloride generating highly selective (Z)-N-(2-halophenyl)-3-(dime- thyllamino)-2-aryloxyacrylamides, and the step two undergoes copper iodide catalyzed intramolecular C-O bond formation to yield title compounds. This strategy is not only providing newly discovered key intermediates 6a-l which contain multiple functional groups on 2-position (as building blocks), but also expanded the scope of methodologies for making diverse benzoxazoles with multiple functional groups.

■ Synthesis and Biological Evaluation of New Curcumin Analogs Inhibiting Osteoclastogenesis

Aoi Sugawara, Toshika Ohashi, Satoshi Ogawa, Naomi Matsumoto, Mayumi Nakanishi-Matsui, Satoru Tamura, and Tomikazu Kawano*

*Department of Medicinal and Organic Chemistry, School of Pharmacy, Iwate Medical University, 1-1-1 Idaidori, Yahaba , Iwate, Japan

Abstract

A series of curcumin analogs (1-3) were newly designed and synthesized for the development of therapeutic agents for osteoporosis. Among the synthesized compounds, 2,5-substituted conjugated thiophene derivative (1a) and the corresponding pyrazine derivative (1c) were shown to be potential leads for the development of anti-osteoclastogenesis agent.

■ When Hydrazonoyl Chlorides Meet Terminal Alkynes: Regioselective Copper(I)-Catalysed "Click" Sequential Reactions to 5-Substituted Pyrazoles

Giorgio Molteni*

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

Abstract

In the presence of catalytic amounts of copper(I) salts, terminal alkynes underwent the formation of copper(I) acetylides that enabled their nucleophilic addition onto hydrazonoyl chlorides followed by spontaneous cyclisation of the resulting alkynylhydrazone intermediate. This sequential reaction sequence was exploited as a facile and regioselective synthesis of 1,3,5-substituted pyrazoles. A catalytic cycle has been proposed accounting for the observed results.

■ Three New Benzazepine Alkaloids from Thalictrum cirrhosum and Their Anti-Rotavirus Activity

Qiu-Fen Hu, Dian Luo, Na Lv, Ya-Ning Zhu, Lu Liu, Fan Wu, Dong Miao, Wei-Guang Wang, Qian Gao, Min Zhou,* and Guang-Yu Yang*

*Technical center, China Tobacco Yunnan Industrial Co., Ltd., Keyi Road 41#, China

Abstract

Three new benzazepine alkaloids, cirrhobenzazepines A-C (1-3), together with four known alkaloids (4-7) were isolated from the whole plants of Thalictrum cirrhosum. Their structures were elucidated by spectroscopic methods, including extensive 1H, 13C, and 2D-NMR techniques. Compounds 1-7 were tested for their anti-rotavirus activity. The results revealed that compounds 1-7 exhibited potent anti-rotavirus activity with TI valves in the range of 11.9-18.2, respectively.