HETEROCYCLES

■ Contents

■ Imidazole Chemistry in Crop Protection

Clemens Lamberth*

*Syngenta Crop Protection AG, Research Chemistry, Schaffhauserstrasse 101, CH-4332 Stein, Switzerland

Abstract

An overview is given of the significance of the imidazole scaffold in crop protection chemistry. The main herbicidally, fungicidally and insecticidally active imidazole classes are presented, together with their synthesis routes, modes of action and biological efficacies. Also, partially and fully saturated imidazole derivatives, such as imidazolines and imidazolidines, oxygenated derivatives, such as imidazolinones and hydantoins as well as annulated derivatives, such as benzimidazoles, are covered. In addition, also the role of imidazoles as intermediates or reagents in the synthesis of other agrochemicals is reported.

■ Recent Advances in Synthetic Transformations with Robust Yet Reactive B(dan) Moiety

Jialun Li and Hiroto Yoshida*

*Graduate School of Advanced Science and Engineering, Hiroshima University, Higashi-Hiroshima 739-8526, Japan.

Abstract

Recent advances in the direct B(dan)-installing reactions (dan = naphthalene-1,8-diaminato) into organic frameworks by utilizing (pin)B–B(dan) or H–B(dan) as a B(dan) source, and the direct cross-coupling of dan-substituted organoboron compounds therefrom are described.

■ Synthesis of Tetraphenyl-furoindoles via Tandem Reactions

Shi-Yun An, Jin-Long Zhang, and Gao-Xi Jiang*

*State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. of China

Abstract

We report a novel one-step synthesis of tetraphenyl substituted furoindoles involving acid-catalyzed cascade approach of commercially available m-aminophenols with readily accessible α-hydroxyaldehydes. The tandem reactions involved nucleophilic addition, aldimine condensation, pinacol rearrangement, α-iminol rearrangement, cyclization and dehydration aromatization process. The yield of furoindoles was up to 75%.

■ Synthesis and Biological Activities of Selenium/Thioether Quinazoline Compounds

Canjun Yan, Yuchun Zhang, Guihan Zhao, Xiaohong Jin, Wuwei Yang, Pengpeng Niu, Haojie Wang, and Gang Liu*

*School of Chemistry and Materials Science, Ludong University, Yantai 264025 China

Abstract

In view of the important role of quinazoline skeletons in anti-cancer drugs like Gefitinib and the vital importance of organoselenium compounds in biomedicine field, in this protocol, twenty quinazoline selenium derivatives were designed and synthesized with the aim to develop new anti-cancer drugs by utilizing the synergistic effects of quinazoline skeleton and selenium. In addition, the synthetic method of thioether substituted quinazolines was improved. The biological activities of title compounds were determined against A549 cancer cells in vitro by using MTT assay at 1 μM and 10 μM concentrations. The results showed that most of the title compounds had good anticancer activities. Of note, 6-chloro-4-benzylselenoquinazoline (G5) exhibited better inhibitory activity (67.8% inhibition ratio) than the positive control drug Gefitinib (62.9% inhibition ratio) at the concentration of 10 μM. These findings will provide some clues for further research of anticancer drugs.

■ Synthesis, Characterization, and DRAK2 Inhibitory Activities of Hydroxyaurone Derivatives

Mingsheng Zhao, Chengqiu Dai, Yi Li, Yinan Liu, Jing-Ya Li,* and Xueling Hou*

*State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China

Abstract

We reported the synthesis of 25 derivatives of hydroxyaurone, which were characterized by 1H NMR, 13C NMR, high resolution mass spectrum, and single crystal X-ray diffraction analysis. Their activities on the death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2) were evaluated by kinase detection kit at a dosage of 5μM. Most of the synthetic hydroxyaurones exhibited moderate to good inhibitory activities. The IC50 value ranged from 0.81 to 2.42 μM when the structure of aurone's B ring was kept unchanged and its A ring was substituted by hydroxyl groups. On the contrary, modification of the aurone's B-ring with hydroxyl groups lead to the IC50 value ranging from 1.15 to 17.5 μM. This indicates presence of hydroxyl group of the B ring is crucial for aurone's DRAK2 kinase inhibitors. Therefore, hydroxyaurone may serve as a new possible lead compound for the discovery of DRAK2. Further pharmacological investigations are underway and will be reported in due course.

■ Alternative Approach to the 2-Oxopyrano[3,2-c]quinoline Core

Alexa Redway, Roxanne Higgins, Yvette Jackson, and Nadale Downer-Riley*

*Department of Chemistry, the University of the West Indies, Mona, Kingston 7, Jamaica

Abstract

An alternative route to access the pyrano[3,2-c]quinoline or benzo[7,8]-6-azacoumarin core form readily available quinoline N-oxides is presented. The key reaction involves an unusual rearrangement of tetrahydroquinoline-2-ylacetic acids in the presence of triethylamine and acetic anhydride.

■ Multicomponent Reaction for the Synthesis of 1,2,3,4,6-Pentasubstituted Piperidines Catalyzed by NIS

Liu Pengpeng*

*School of Petroleum and Chemical Engineering, Dongying Vocational Institute, Dongying, 257091, China

Abstract

An efficient, suitable and high yielding method has been developed for the synthesis of substituted piperidines via multicomponent, one-pot domino reaction of β-keto ester, aromatic amines, and aromatic aldehydes in the presence of catalytic amount of N-iodosuccinimide (NIS) in ethanol. Atom economy, mild reaction conditions, good to excellent yields, operational simplicity and easy work-up are some of the important features of this method.

■ Total Synthesis of Hyalodendriol C

Ishtiaq Jeelani,* Katsunori Itaya, and Hitoshi Abe

*Graduate School of Innovative Life Science, University of Toyama, 3190 Gofuku 930-8555, Japan

Abstract

We present a total synthesis of hyalodendriol C, a fungal natural product. We have focused on the use of palladium-catalyzed intramolecular biaryl coupling reaction of phenyl benzoate derivatives to synthesize hyalodendriol C. Keeping in view, the indispensable biological values of this compound, we took the advantage of our established strategy to chemically synthesize hyalodendriol C. The total synthesis of hyalodendriol C got accomplished in 10 steps beginning with the preparation of phenol derivative from the commercially available 5-methylbenzene-1,3-diol and synthesis of the corresponding benzoic acid derivative.

■ Diterpenoid Alkaloids from Aconitum leucostomum and Their Antifeedant Activity

Jue Wang, Jin-bu Xu, Hong-bo Yang, Feng Gao, Xian-li Zhou, Lin Chen,* and Shuai Huang*

*School of Life Science and Engineering, Southwest Jiaotong University, Southwest Jiaotong University, Chengdu, 610031, China

Abstract

Two new diterpenoid alkaloids and eight known ones were isolated from the root of Aconitum leucostomum. Their structures were elucidated on the basis of extensive spectroscopic analyses such as HR-ESI-MS, 1D NMR and 2D NMR spectra. Compounds 1, 2, 5, 6 and 8 were tested for their antifeedant activity against Spodoptera exigua Hübner, and compound 2 showed antifeedant activity with an effective concentration for 50% feeding reduction (EC50) at 1.54 mg/cm2.

■ Three New Anti-Rotavirus Quinoline Alkaloids from the Whole Plant of Thalictrum glandulosissimum

Qiu-Fen Hu, Fan Wu, Ya-Ning Zhu, Lu Liu, Ming-Xin Liu, Bing-Biao Cai, Man-Fei Li, Dong Miao, Min Zhou,* and Guang-Yu Yang*

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, Yunnan Minzu University, Kunming 60500, P. R. China

Abstract

Three new quinoline alkaloids, 4-acetyl-6-methyl-7-(3-methyl-2-oxobut-3-enyl)quinolin-2(1H)-one (1), 4-acetyl-5-methyl-7-(3-methyl-2-oxobut-3-enyl)quinolin-2(1H)-one (2), and 4-acetyl-6-methyl-7-prenylquinolin-2(1H)-one (3) were isolated from the whole plants of Thalictrum glandulosissimum. Their structures were elucidated by spectroscopic methods, including extensive 1H, 13C, and 2D-NMR techniques. Compounds 1-3 were also tested for their anti-rotavirus activity. Compounds 1-3 exhibited potent anti-rotavirus activity with therapeutic index (TI) valves of 17.6, 15.0, and 23.6 respectively.

■ Synthetic Approaches for Nitrogen Bridgehead Pyrido-[1,2-b][1,2,4]triazepines and Annulated Compounds Using 4-(8-Allylchromon-3-yl)-1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile

Magdy A. Ibrahim*

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy 11757, Cairo, Egypt

Abstract

Some new nitrogen bridgehead pyrido[1,2-b][1,2,4]triazepines linked 8-allylchromone moiety have been synthesized from reaction of novel 4-(8-allyl-chromon-3-yl)-1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (3) with a variety of α,γ-bifunctional electrophiles including dibenzoylmethane, ethyl benzoylacetate, 3-[bis(methylthio)methylidene]pentane-2,4-dione, 2-cyano-3,3-bis(methylthio)acrylonitrile, 2-cyano-3,3-bis(methylthio)prop-2-enamide, 5-chloro-3-methyl-1-phenylpyrazole-4-carboxaldehyde, 2-chloro-3-formyl-quinoline, (p-methoxybenzylidene)malononitrile and ethyl 2-cyano-3-(4-methoxyphenyl)prop-2-enoate. Some novel pyrazolo[3,4-e]pyrido[1,2-b]-[1,2,4]triazepines were also synthesized. Structures of the newly synthesized products have been deduced upon the help of elemental analysis and spectral data (IR, 1H NMR, 13NMR, mass spectra).