HETEROCYCLES

■ Contents

■ Highly Oxidized γ-Lactam-Containing Natural Products: Total Synthesis and Biological Evaluation

Kosaku Tanaka III,* Hiroshi Kogen, and Kenichi Kobayashi*

*Graduate School of Pharmaceutical Sciences, Health Sciences University of Hokkaido; 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan

Abstract

γ-Lactam is a ubiquitous structure found in the natural products. A number of highly oxidized γ-lactam-containing natural products are produced by various fungi. These compounds often show a wide range of biological activities because their multiple internal reaction sites, which arise from the high oxidation state of the compounds, can react with biological nucleophiles. Due to their high reactivity and dense functionality, total syntheses of these molecules require strict control of the inherent reactivity and the appropriate design of synthetic intermediates. This review focuses on the recent total syntheses of some highly oxidized γ-lactam-containing natural products, including fused bicyclic (epolactaene, NG-391, lucilactaene, L-755,807), spirocyclic (azaspirene, pseurotin A, E, and F2, cephalimysin A–C, FD-838, and berkeleyamide D), and tricyclic (rubrobramide and talaramide A) skeletons, and on the structure-activity relationship studies of related molecules.

■ Debromooscillatoxins G and I from the Cyanobacterium Moorea producens

Kanon Iguchi, Masayuki Satake, Yutaro Nishio, Bo-Tao Zhang, Kento Kawashima, Hajime Uchida, and Hiroshi Nagai*

*Department of Ocean Sciences, Tokyo University of Marine Science and Technology, Tokyo 108-8477, Japan

Abstract

Debromooscillatoxins G and I (1 and 3) were isolated from the marine cyanobacterium Moorea producens collected in Okinawa. Their structures were determined based on spectroscopic data, including nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS). Both the isolated compounds showed moderate cytotoxicity and diatom growth inhibition at a concentration of 10 µg/mL.

■ Novel Reaction Course of Thiiranes to Vinyloxiranes: Reaction of Benzyne with Thiiranes and Aldehydes

Kentaro Okuma,* Yuxuan Qu, and Noriyoshi Nagahora

*Department of Chemistry, Fukuoka University, Jonan-ku, Fukuoka 814-0180

Abstract

Reaction of 2 molar amount of 2-(trimethylsilyl)phenyl triflate with thiiranes and aldehydes in the presence of CsF afforded vinyloxiranes in one-pot operation. Reaction of benzyne with thiiranes gave the corresponding alkenyl phenyl sulfides, which further reacted with another molar of benzyne to afford sulfonium ylide intermediates. Further treatment of aldehydes gave the corresponding vinyloxiranes.

■ Uncommon Reactivity of a Seco-Oxacassane Diterpenoid and Antiproliferative Activity of Some Derivatives

Alexia Hernández-Jiménez, Ledy De-la-Cruz-Martínez, Raúl Velasco-Azorsa, Reyna Zeferino-Díaz, José G. Alvarado-Rodríguez, Luis H. Mendoza-Huizar, J. Jesús Manríquez-Torres, Horacio Almanza-Reyes, Carlos M. Cerda-Garcia-Rojas, Pedro Joseph-Nathan, and J. Martín Torres-Valencia*

*Área Académica de Química, Universidad Autónoma del Estado de Hidalgo, km 4.5 Carretera Pachuca-Tulancingo, Mineral de la Reforma, Hidalgo 42184, México

Abstract

The main diterpenoid of Acacia schaffneri, 7,8-seco-7,8-oxacassa-13,15-dien-7-ol-17-al (1), has two aldehydes of which one is protected as a ε-lactol. The free aldehyde resisted to afford the carboxylic acid using reagents with different oxidative strength, although 1 gave oxime 2 when treated with hydroxylamine, β-hydroxyketone 3 after addition of acetone, aldo-ε-lactone 4 whereby only the lactol was oxidized when using Jones reagent, and epoxyformate 5 after Baeyer-Villiger treatment. Hydrolysis of 5 with NaHCO3 gave 6. Structures 2–6 followed from physical and spectral data including X-ray diffraction. All compounds showed antiproliferative activity similar to some chemotherapeutic drugs against C2C12, L929, SiHa, and MDA-MB-231 cell lines.

■ Preparation of Pyridine Derivatives from the Corresponding 5-Acetal-1-carbonyl Compounds by Acid Promoted Cyclization

Hiromichi Mihara, Yuki Watanabe, and Hiroyuki Konno*

*Department of Biological Engineering, Graduate School of Science and Engineering, Yamagata University, Yonezawa, Yamagata 992-8510, Japan

Abstract

The synthesis of four alkylpyridine derivatives from 5-acetal-1-carbonyl compounds via the one-pot, acid-promoted cyclization of oxime intermediates is described. In addition, a dihydroxypyridine and pyridinium salt were also synthesized. The pyridine formation step was not affected by the stereochemistry of the precursors used.

■ A New Denudatine Type C20-Diterpenoid Alkaloid from Aconitum fischeri var. arcuatum

Lili Qin, Feng Xing, Lin Chen,* and Xianli Zhou*

*School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, People’s Republic of China

Abstract

A new denudatine-type C20-diterpenoid alkaloid bearing a rare C-15 ketone carbonyl and 16,17-epoxy group, named arcutisine (1), together with 24 known compounds (2-25), were obtained from the roots of Aconitum fischeri var. arcuatum. Their structures were established by various spectroscopic analyses. Among them, compounds 1 and 2 were both isolated from a natural source for the first time. Besides, compounds 7 and 10 showed weak effect on anti-inflammatory activity with the inhibition rate of 33.5% and 33.7% at the concentration of 40 µM.

■ Biological Evaluation and Synthesis of Thiazole Schiff Base Derivatives

Wei Zhou, Fengyan Wu, and Jinbing Liu*

*School of Food and Chemical Engineering, Shaoyang University, Shao Shui Xi Road, Shaoyang 422100, PRC

Abstract

In this study, we report the synthesis of thiazole Schiff base derivatives (Z1-Z16) and their tyrosinase inhibitory activity, anti-oxidant activities. Mushroom tyrosinase inhibitory assay showed compound Z8 (IC50 = 2.78 ± 0.08 μM) inhibited tyrosinase more than kojic acid (49.39 ± 0.17 μM), and docking study indicated compound Z8 (-7.32 kcal/mol) had stronger binding affinities for tyrosinase than kojic acid (-5.7 kcal/mol). Phenolic hydroxyl group on 4-position (R2) of compound Z8 can form Metal - Acceptor with Cu401. The results of inhibition kinetics studies demonstrated that compound Z8 was mixed type inhibitor. The anti-browning effects manifested compound Z8 expressed satisfactory effects in anti-browning of fresh-cut apples and fresh-cut potato. All the results indicated that thiazole Schiff base derivatives might be promising leading compounds as tyrosinase inhibitors and anti-oxidant agents.

■ Synthesis and Reaction of Novel Spiro Pyrazol-3-ones Containing Oxirane Moiety

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

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

Abstract

An efficient synthesis and reaction of a series of spiro pyrazol-3-one derivatives containing oxirane moiety are described. The convenient substrates, three types of pyrazole-4,5-diones, were reacted with phenacyl bromides in the presence of triethylamine in ethanol at room temperature to give the corresponding spiro epoxide-pyrazol-3-ones in moderate to good yields. Furthermore, thermal treatment of spiro compounds with pyrrolidine in the presence of water caused ring transformation easily to afford the corresponding pyridazinone derivatives. These methods provide several advantages such as operational simplicity, shorter reaction time, and higher yields. All the synthesized compounds were characterized by spectroscopic analysis.

■ Synthesis and Biological Activity Evaluation of Imidazole Heterocyclic Sulfonylurea Compounds

Wei Li, Jinze Pei, Yang Chen, and Guangshan Xuan*

*College of Chemical Engineering, Qingdao University of Science & Technology, 53 Zhengzhou Road, Shibei District, Qingdao, Shandong Province, China

Abstract

Sulfonylurea herbicides are the most widely used herbicides in the world. They have the advantages of high efficiency, good selectivity, and no toxicity to human and animals. In this study, sulfonylureas containing imidazole heterocycles were synthesized on the basis of computer simulation of molecular docking, and the biological activity was evaluated. It shows that the compound has a good inhibitory effect on the ALS and a certain inhibitory effect on the phytopathogenic fungi of Curvularia lunata and Curvularia mebaldsii. Its inhibitory rate at concentration of 50 mg/L is similar to that of the carbendazim. This research provides the basis for further optimization of the structure of imidazolium heterocyclic sulfonylurea and the synthesis of its derivatives.

■ Direct Construction of 9-Amino-7-aryl-6H-benzo[c]chromene-8,10-dicarbonitriles by Means of a Cascade Michael/Cyclization Reaction

Dao-Cal Wang,* Yi Luo, Xi-Xia Chen, and Xiao-Peng Liu*

*Hubei Key Laboratory of Biologic Resources Protection and Utilization, School of Biological Science and Technology, Hubei Minzu University, Enshi 445000, China

Abstract

An easy and practical synthesis method was developed for the preparation of potentially biologically active 9-amino-7-aryl-6H-benzo[c]chromene-8,10-dicarbonitriles. Starting from chroman-4-one derivatives, aldehydes and malononitrile, the one-pot three-component reaction went on smoothly in the presence of DBU at 60 °C for 32 hours using tetrahydrofuran as solvent. More diverse 9-amino-7-aryl-6H-benzo[c]chromene-8,10-dicarbonitriles were synthesized and separated in good yields. The outstanding advantages of this demonstrated method mainly reflects in the easy access to starting materials, high atom economical manner, simple operation steps and wide applicability.

■ Synthesis of One Covalent Organic Framework (COF) Based on C=N Bonds and Its Excellent Performance of Iodine Adsorption

Yingbin Zhang, Limei Li, Meige Wang, and Zhongyu Duan*

*School of Chemical Engineering, Hebei University of Technology, 1 Dingzigu Road, Tianjin, 300130, China

Abstract

Radioactive iodine is one of the main substances existed in nuclear wastes. It can quickly diffuse into the atmosphere causing great harm to environment and human health. Therefore, how to capture radioactive iodine efficiently has become a research hotspot. Herein, a covalent organic framework (COF) material (COF-1) has been synthesized by aldimine condensation reaction using the 1,3,5-triazine structure compound and isophthalaldehyde as starting materials. The nitrogen-rich COF-1 possesses medium specific surface area (321.78 m2/g), a pore diameter of 1.98 nm and relatively regular layered stack structure, which provide good conditions for iodine adsorption ability. The maximum iodine uptake of COF-1 is 2647 mg/g, which is higher than most iodine adsorbents reported. Subsequently, the release of iodine can be achieved in methanol indicating the iodine adsorption of COF-1 is a reversible process. It is also shown that COF-1 can be recycled. These characteristics maybe make COF-1 materials as a good iodine capturer in practical applications.

■ Metal-Free Regioselective Synthesis of 2-Nitro-3-arylimidazo[1,2-a]pyridines via Oxidative Amination under Air Using Silica Sulfuric Acid as an Effective Heterogeneous Catalyst

Divya Sree Uppalapati,* Rama Sekhara Reddy Dachuru,* and Satya Veni Sunkara

*Department of Chemistry, University College of Engineering Kakinada, Jawaharlal Nehru Technological University Kakinada, Kakinada 533003, Andhra Pradesh, India

Abstract

Metal-free regioselective strategy for the synthesis of 2-nitro-3-arylimidazo[1,2-a]pyridines from β-nitrostyrene and 2-aminopyridines under aerobic conditions using silica sulfuric acid (SSA) as heterogeneous catalyst has been developed. The synthetic methodology provides the title compounds with good yields under mild conditions, and complete regioselectivity is observed. Furthermore, SSA was not used previously for this transformation.