HETEROCYCLES

■ Contents

■ Modified Dehydroellagitannins from Davidia involucrata Leaves

Akari Esumi, Hiroe Aoyama, Yuuki Shimozu, Shoko Taniguchi, and Tsutomu Hatano*

*Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

Davidia involucrata (Nyssaceae) is a naturally rare plant found in southern China. We isolated two previously undescribed ellagitannins, davicratinic acid B (5) and C (6), in addition to four known compounds, davicratinic acid A (1), helioscopinin B (2), granatin A (3), and pedunculagin (4). Spectral analyses revealed that compounds 5 and 6 are modified dehydroellagitannins with isomeric structures.

■ Divergent Synthesis of Indole-2-carboxylic Acid Derivatives via Ligand-Free Copper-Catalyzed Ullmann Coupling Reaction

Jiadi Zhou, Yongjian Chen, Junsong Huang, and Jianjun Li*

*Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, P. R. China

Abstract

This article describes a ligand-free copper-catalyzed Ullmann coupling reaction for the preparation of divergent indole-2-carboxylic acid derivatives including esters, amides and anhydrides. Various compounds 3, which could be synthesized from aldehydes conveniently, were used as substrate to provide the corresponding indole-2-carboxylic acid derivatives in moderate to good yields.

■ Synthesis and Antimicrobial Evaluation of Some Novel Heterocycles as Antipyrine Derivatives

Khaled S. Mohamed* and Elsherbiny H. El-Sayed

*Engineering Chemistry Department, Higher Institute for Engineering and Technology, New Damietta, New Damietta 34518, Egypt

Abstract

Novel antipyrine derivatives bearing pyran, pyridopyrimidine, chromene, benzothiazole, indole, pyrazole and pyridazine moieties were synthesized by using 2-cyano-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide (1) as a staring material. The newly synthesized compounds were evaluated for their antimicrobial activities based on inhibition diameter zone against Gram-positive and Gram-negative bacteria.

■ Synthesis of Aminated Cyclotriphosphazenes. Solvent Effects on the Product-Selectivity of the Amination

Manabu Kuroboshi,* Masahiko Morita, Yasunari Masumoto, Masaki Mikasa, Ryohei Toza, and Hideo Tanaka

*Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka 3-1-1, Kita-ku, Okayama 700-7530, Japan

Abstract

We investigated the reaction between hexachlorocyclotriphosphazene ((NPCl2)3) and gaseous ammonia in several solvents to find that (NPCl2)2(NP(NH2)2) was obtained in solvents having low dielectric constant such as toluene and ether, whereas novel compound, (NPCl2)(NP(NH2)2)2, was selectively obtained in solvents having high dielectric constant such as acetonitrile.

■ Synthesis of Arylthiochlorocyclotriphosphazenes

Manabu Kuroboshi,* Masaki Mikasa, and Hideo Tanaka

*Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka 3-1-1, Kita-ku, Okayama 700-7530, Japan

Abstract

We investigated the reaction between hexachlorocyclotriphosphazene ((NPCl2)3: HCCP) and thiols in the presence of bases. In MeCN/Et3N, two and/or four arylthio units were introduced in gem-mode selectively by controlling the amount of thiols: thus, HCCP was treated with 2 and/or 4 equivalents of ArSH/Et3N in MeCN to afford 2,2-dithiolated and/or 2,2,4,4-tetrathiolated products, respectively. Neither mono-thiosubstituted products, tri-thiosubstituted products, nor regioisomers (non-geminal products) were obtained. In contrast, when other solvents such as THF and Et2O or other bases such as NaH or K2CO3 were used, a mixture of dithiolated products, tetrathiolated products, and hexathiolated products was obtained.

■ Secalonic Acids J–M, Four New Secondary Metabolites from the Marine-Derived Fungus Penicillium oxalicum

Li Chen, Zhi-Hao Lu, Qin-Ying Liu,* Qiu-Hong Zheng, Lin Du, and Qi-Qing Zhang*

*Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, P. R. China

Abstract

Four new secalonic acid derivatives, secalonic acids J–M (1–4), were isolated from the marine-derived fungus Penicillum oxalicum. The planar structures of these compounds were elucidated by NMR and high-resolution mass spectrometric analyses. The absolute configurations were established by comparison of their experimental and calculated electronic circular dichroism spectra. Finally, these compounds were further evaluated for cytotoxic activities against the selected cancer cell lines in vitro. The results of flow cytometry demonstrated that compound 1 owned moderate activity of inducing apoptosis against HeLa cell.

■ A Convenient Approach to the Synthesis of Novel Tricyclic Fused Furo[2,3-b]pyridine Derivatives

Fumi Okabe-Nakahara,* Kazuhiro Tomoike, Hayate Nagabuchi, Eiichi Masumoto, Hiroshi Maruoka, and Kenji Yamagata

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

Abstract

The synthesis of novel tricyclic fused furo[2,3-b]pyridine derivatives is described. 3-Cyano-4,5-dihydro-2-furan(and 2-thiophene)acetonitriles 1,2 were reacted with phenacyl bromides to give 5'-arylfuran-2'-amines 3,4. Compounds 3,4 were intramolecularly cyclized in the presence of sodium ethoxide to yield tricyclic fused furo[2,3-b]pyridine derivatives 5,6. Furthermore, one-pot synthesis of compounds 5,6 from starting materials 1,2 is also developed.

■ Semisynthesis of Triptolide Analogues Part IV: Effects of C-14 Carbamothioate Substituents on Cytotoxic Activities

Yutaka Aoyagi,* Mizuki Murase, Chihiro Kuwahara, Reiko Yano, Ritsuo Aiyama, Takeshi Matsuzaki, Shusuke Hashimoto, Haruhiko Fukaya, Koichi Takeya, and Yukio Hitotsuyanagi*

*College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya 463-8521, Japan

Abstract

Four C-14 carbamothioate triptolide analogues were prepared and their cytotoxic activities on A549 human lung tumor cells and HT29 human colon tumor cells were evaluated. The activities of the prepared compounds were weaker than those of the parent compound, triptolide (1). However, some differences were noted in the activities of prepared compounds. The leaving ability and bulkiness of the amine components of their carbamothioate groups appeared to affect their cytotoxic activities.

■ Fragilides M–O, New Triacetoxybriaranes from the Gorgonian Coral Junceella fragilis (Ellisellidae)

Chia-Cheng Lin, Wu-Fu Chen, Gene-Hsiang Lee, Zhi-Hong Wen, Lee-Shing Fang, Yueh-Hsiung Kuo, Chieh-Yu Lee,* and Ping-Jyun Sung*

*Department of Planning and Research, National Museum of Marine Biology and Aquarium, 2 Houwan Road, Checheng, Pingtung, Taiwan 944, Taiwan

Abstract

Chemical investigation of the ethyl acetate-soluble fraction from the methanol/dichloromethane extract of a sea whip gorgonian coral Junceella fragilis afforded four polyacetoxybriaranes, including a known metabolite, junceellin (1), along with three new analogues, fragilides M–O (2–4). The absolute configuration of 1 was determined by X-ray analysis and the structures of 2–4 were elucidated on the basis of spectroscopic methods.