HETEROCYCLES

■ Contents

■ Recent Advances in Synthetic Hetaryne Chemistry

Yu Nakamura, Suguru Yoshida,* and Takamitsu Hosoya*

*Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10, Surugadai, Kanda, Chiyoda-ku 101-0062, Japan

Abstract

Recent advances in synthetic hetaryne chemistry are reviewed. Various methods for the generation of hetaryne intermediates from several types of precursors enabled facile syntheses of a broad range of heteroaromatic compounds including natural products.

■ Microwave-Assisted Synthesis of 1,3,5-Triazines: Efficient Approaches to Therapeutically Valuable Scaffold

Ahmad Junaid and Anton V. Dolzhenko*

*School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia

Abstract

1,3,5-Triazine ring is an important scaffold for the construction of new biologically active compounds. Microwave irradiation has found an extensive application in organic and medicinal chemistry accelerating reactions and drug discovery process. This review systematizes methods for the microwave-assisted construction of 1,3,5-triazine ring and discusses their advantages and disadvantages over methods based on the conventional heating.

■ Synthesis, Characterization, and Electronic and Structural Calculations of Some 1,4-Disubstituted Cyclopenta[d][1,2]oxazines

Nathan C. Tice,* Steven Wild, Christian Olmstead, Edwin D. Stevens, Bangbo Yan, Hannah Brooks, and Judith L. Jenkins

*Department of Physical Sciences, The University of Findlay, 1000 North Main Street, Findlay, OH 45840, U.S.A.

Abstract

Our current work focuses upon the formation and characterization of some 1,4-disubstituted cyclopenta[d][1,2]oxazines via ring closure with hydroxyl amine on a 1,2-diacyl cyclopentadiene precursor. Recently, we formed and characterized two fused-ring disubstituted oxazines (R = thienyl, 4-chlorophenyl) in high yield, which serve as precursors towards oxazine-based conducting polymers. X-ray crystallographic analysis of the thienyl oxazine did show favorable π-π stacking, critical to effective intermolecular charge transfer. To further evaluate its electronic and optical properties, theoretical calculations were performed on the thienyl oxazine, including Natural Bond Orbital analysis. Calculated values suggest a strong potential for Non-Linear Optical applications.

■ Chemoselectivity-Tunable [5 + 2] Cycloadditions of Allenamides and Oxidopyryliums

Min Yang, Liangliang Kang, and Shuzhong He*

*School of Pharmaceutical Sciences, Guizhou University, 440 Chongyi Building,Guizhou University, Huaxi District, China

Abstract

[5 + 2] Cycloadditions between allenamides and oxidopyryliums are described. A series of substituted cycloheptanones were synthesized by this method with moderate to good yields. Interestingly, the chemoselectivity of this reaction could be tuned by changing the electron-withdrawing groups on the allenamide nitrogen atom. When oxazolidinone chiral auxiliaries were introduced in the allenamide substrate, [5 + 2] cycloadducts could be obtained with high diastereoselectivities. This reaction provides a useful synthetic protocol for the construction of highly substituted seven-membered rings.

■ Synthesis and Evaluation for Biological Activities of 2-Thio-Acylated Thiazoles Containing Pyrazole Moiety

Eiichi Masumoto, Nobuhiro Kashige, Hayate Nagabuchi, Fumi Okabe-Nakahara, and Hiroshi Maruoka*

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

Abstract

An approach to the synthesis of novel 2-thio-acylated thiazoles containing pyrazole moiety is described. The pyrazole-thiazolethione derivative as the key building block for bis-heterocycles was formed via a Knoevenagel-type condensation of rhodanine with pyrazol-3-one. Thermal treatment of the pyrazole-thiazolethione derivative with acid anhydride and/or chloride in refluxing toluene caused diacylation reaction to give the corresponding 2-thio-acylated thiazoles containing pyrazole moiety. All the synthesized compounds were characterized by spectroscopic analysis and were tested for their DNA cleavage activity in vitro. Furthermore, they were evaluated for their antifungal activity against Candida albicans and Saccharomyces cerevisiae.

■ Pentenyl Coumarins from the Roots and Stems of Yunnan Local Sun Cured Tobacco and Their Bioactivity

Qiu-Fen Hu,* Dian Luo, Na Lv, Yin-Ke Li, Wei-Song Kong, Jing Li, Xin Liu, Qian Gao, Guang-Yu Yang, Hai-Ying Xiang,* and Ju-Xing Jiang*

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650031, China

Abstract

Three new (1-3), together with two known (4 and 5) pentenyl coumarins were isolated from the roots and stems of Yunnan local sun cured tobacco. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1~5 were tested for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compound 2 showed strong inhibition with inhibition zone diameter (IZD) of 18.6 ±2.6 mm, and compounds 1, 3, 4, and 5 showed good inhibition with IZD of 14.2±2.2, 14.8±2.3, 12.4 ±2.2, and 15.1±1.8 mm, respectively. Compounds 1-5 were also tested for the antioxidant activity, and they showed notable antioxidant activity with IC50 values of 4.92, 4.18, 4.43, 4.65, and 4.07 μg/mL, respectively

■ Synthetic Strategy to New Terphenyl-Type Bis-Pyrrole Arenes Starting from Highly Electron-Deficient 4-Nitroanilines with 1,4-Diketones

Hyejeong Lee, Seolhee Bae, Eungyung Kim, Jihye Park, and Byeong Hyo Kim*

*Department of Chemistry, Kwangwoon University, 447-1, Wolgye-Dong Nowon-ku, Seoul, 139-701, Korea

Abstract

A new synthetic method for converting highly electron-deficient 4-nitroanilines into terphenyl-type bis-pyrrole arene derivatives has been developed, which is not easy to accomplish using conventional methods because of their poor reactivity. This process involves an indium-mediated reductive cyclization reaction of highly electron-deficient 2,6-disubstituted nitroanilines in the presence of a 1,4-diketone to form 2,6-disubstituted 4-(1H-pyrrole-1-yl)anilines followed by cyclization with another 1,4-diketone to give the target bis-pyrrole arene products in moderate to high yield.

■ Studies toward Identifying the Pharmacophore of L-755,807 for Amyloid-β Aggregation Inhibitory Activity

Kenichi Kobayashi,* Kosaku Tanaka III, Yusuke Honma, Momoko Suzuki, and Hiroshi Kogen*

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

Abstract

To investigate the structure–activity relationship of L-755,807 for amyloid-β aggregation inhibitory activity, L-755,807 analogs were synthesized and biologically evaluated. The results suggest that a hydrophobic conjugated carbon chain with a terminal hydrophilic functional group is essential for the potent activity. These findings provide a starting point for identifying the pharmacophore of L-755,807.