HETEROCYCLES

■ Contents

■ New and Practical Applications of Functionalized Cyclotriphosphazene Core-Based Materials

Manabu Kuroboshi* and Hideo Tanaka

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

Abstract

Hexachlorocyclotriphosphazene (HCCP) is a very old compound, and used as a starring material of a variety of cyclotriphosphazene derivatives. Some of them have unique properties, and have been used in not only frame retardants but also functional materials and biomaterials. To develop cyclotriphosphazene derivatives having a desired function, numbers of substituents, regio-, and stereochemistry should be controlled in the reaction between HCCP and nucleophiles. In this review, selectivity in the reaction between HCCP and nucleophiles as well as application of the cyclotriphosphazene derivatives are summarized.

■ An Efficient Synthesis of Some New Coumarin Hybrids Endowed with Expected Biological Activity

Mohamed A. Raslan,* Noura Sh. Hagaggi, Kamal M. Dawood, Hany A. Abdel Atty, and Ayman Nafady

*Department of Chemistry, Faculty of Science, Aswan University, Aswan 81528, Egypt

Abstract

Reactions of 5-bromo-2-hydroxybenzaldehyde with cyanoacetic acid hydrazide derivatives in refluxing ethanol afforded some new chromene-based polyfunctionally substituted heteroaromatics. The antimicrobial activity of some of the obtained products was evaluated. The structures of the newly synthesized compounds were elucidated based on their elemental analyses and spectral data.

■ Design and Synthesis of 4'-Cyano Dideoxy Isonucleosides and Their Activity against HIV-1 and HBV

Kengo Onitsuka, Kakeru Yamaguchi, Ryoh Tokuda, Nobuyo Higashi-Kuwata, Shunsuke Kuwahara, Hiroki Kumamoto, Kenji Maeda, Kazuhiro Haraguchi, Hiroaki Mitsuya, and Shuhei Imoto*

*Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1, Ikeda, Kumamoto-shi, 860-0082, Japan

Abstract

Nucleoside reverse-transcriptase inhibitors are major antiviral agents against HIV-1 and HBV. Here, we describe the synthesis of a novel 4'-cyano dideoxy isonucleoside 6 and its phosphoramidate prodrug 7. Intermediate 16 is a promising precursor for the preparation of isonucleosides bearing substituents at the 4' position with various nucleobases. In addition, 6 and 7 were evaluated for their antiviral properties against HIV-1 and HBV. Compound 7 displayed weak anti-HIV activity (EC50 = 61.4 μM) and had no observed cytotoxicity in two different cell systems.

■ A One-Pot Four-Component Procedure for the Synthesis of Dispiro[tetrahydroquinoline-bis(2,2-dimethyl-1,3-dioxane-4,6-dione)] Derivatives

Zhaohui Xu,* Yexuan Tang, Qiang Xiao, and Chuanwen Liao*

*Department of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, P.R. China.

Abstract

A simple and efficient procedure for the diastereoselective synthesis of dispiro[tetrahydroquinoline-bis(2,2-dimethyl-1,3-dioxane-4,6-dione)] derivatives through one-pot four-component reaction of aromatic aldehydes, 2,2-dimethyl-1,3-dioxane-4,6-dione, arylamines and acetone in the presence of potassium dihydrogen phosphate (KDP) is described. The procedure involves initial Knoevenagel reaction, followed by Diels-Alder, Michael additon and intramolecular reactions. The main advantages of the protocol are the high isolated yields, broad substrate scope, mild conditions, and easy operation.

■ Design and Synthesis of Pentacycloundecane Cage Compound Containing Oxazole Moiety

Sambasivarao Kotha* and Subba Rao Cheekatla

*Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India

Abstract

Here, we have established a new and simple synthetic approach to the pentacycloundecane containing cage oxazole unit in four steps. The synthesis begun with a cheap and readily available materials such as 2,5-dimethoxybenzaldehyde and endo-dicyclopentadiene. This approach relies on Van Leusen oxazole synthesis and [2+2] photocycloaddition as key steps. To the best of our knowledge, this is the first example of Cookson’s dione containing oxazole ring system. Some of these oxazole motifs are useful in bioorganic chemistry and our results are likely to draw the attention of medicinal chemists

■ Identification and Characterization of Chlorine-Containing Briaranes from a Cultured Octocoral Briareum excavatum (Briareidae)

Yi-Lin Zhang, Liang-Mou Kuo, Lo-Yun Chen, Gene-Hsiang Lee, Bo-Rong Peng, You-Ying Chen, Yu-Hsin Chen, Tsong-Long Hwang,* Jyh-Horng Sheu,* 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

Six chlorine-containing briaranes, including two new compounds, briarenols M (1) and N (2), as well as four known metabolites solenolide E (3), briarenolide R (4), excavatolide A (5), and briaexcavatolide F (6), have been isolated from a cultured octocoral identified as Briareum excavatum. The structures of 1 and 2 were established by spectroscopic methods and the absolute configurations of 5 and 6 were confirmed by single-crystal X-ray diffraction analysis. These compounds were subjected into the inhibitory effects on fMLF/CB stimulated superoxide anion generation and elastase release in human neutrophils.

■ Synthesis and Reactions of 3,8-Diphenyl-5-(4-methoxyphenyl)pyrrolo[1,2-c][1,3]thiazolo[3,2-a]pyrimidine-6-carbohydrazide

Kamelia M. El-mahdy and Azza M. El-kazak*

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

Abstract

The reaction of 2-mercaptopyrimidine 1 with phenacyl bromide gave pyrrolothiazolopyrimidine 2, which underwent hydrazinolysis to produce the novel pyrrolo[1,2-c][1,3]thiazolo[3,2-a]pyrimidine-6-carbohydrazide 3. Compound 3 used as a key intermediate for the synthesis of poly fused and isolated systems bearing pyrrolo[1,2-c][1,3]thiazolo[3,2-a]pyrimidine moiety via its reactions with some heterocyclization reagents. Structures of the newly synthesized compounds were established by elemental analysis and spectral data (IR, 1H NMR, Mass spectra and 13C NMR). The prepared compounds would be expected to have biological activities.

■ Some New C3- and Cs-Symmetrical Trialkylamino-substituted 1,3,5-Triazines and Their Biological Evaluation

Shunsuke Shimomura, Yusuke Inoue, Yuki Kawano, Yuka Fujita, Kanae Yamada, Yumemi Matsumoto, Kazumi Yokomizo, Jian-Rong Zhou, Kaori Ota, Nobuko Mibu, Makoto Furutachi, and Kunihiro Sumoto*

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

Abstract

We report the preparation of some new additionally synthesized symmetrical 1,3,5-triazines (TAZ) and the results of biological evaluation of their anti-herpes simplex virus type 1 (anti-HSV-1) activity and cytotoxic activity against Vero cells. All of the new trisubstituted TAZ derivatives 3a-3e showed considerable levels of anti-HSV-1 activity (EC50 = 4.4 ~ 30.3 μM). Among the tested compounds, two compounds (3c-2 and 3d) that have three 3,4-methylenedioxyphenylalkylamino groups showed low levels of cytotoxicity (CC50 > 200 μM) against Vero cells. On the other hand, the C3-symmetrical TAZ derivatives 3a-2, 3b-2 and 3e　showed considerably high levels of cytotoxicity (CC50 = 8.91 ~ 15.2 μM). The structure-activity relationships for anti-HSV-1 activity and cytotoxicity of synthesized single-drug type 2,4,6-trisubstituted TAZ derivatives are also discussed.

■ Change in the Fluorescence of 1,1′-Diaryl-2,2′-biimidazoles upon the Addition of Acid

Shoji Matsumoto,* Seigi Tachibana, and Motohiro Akazome

*Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

The optical properties of a series of 1,1′-diaryl-2,2′-biimidazoles were examined. Different transitions were observed in their fluorescence spectra upon changing the electronic properties of the phenyl ring at the C1 and C1′ positions. The presence of a formyl group on the phenyl ring results in fluorescence via a CT transition with a solvent effect. A bathochromic change was observed when HCl was added to a solution of compound bearing a methoxy group in CH2Cl2, whereas a hypsochromic change was observed in compound bearing a formyl group. These observations were attributed to the protonation, which causes a characteristic change in their biimidazole moieties.

■ Amphirionins-3 and -6, New Polyketides from the Cultured Marine Dinoflagellate Amphidinium Species

Masashi Tsuda,* Ryui Makihara, Mika Minamida, Masayuki Tsuda, Mai Akakabe, Keiko Kumagai, Eri Fukushi, Jun Kawabata, and Takeyuki Suzuki

*Center for Advanced Marine Core Research , Kochi University, Nankoku, Kochi 783-8502, Japan

Abstract

Amphirionins-3 (1) and -6 (2) have been isolated from the marine dinoflagellate Amphidinium species. The structures were elucidated by detail analyses of the spectroscopic data, and chemical conversions. Compounds 1 and 2 exhibited moderate cytotoxic activity against human cervix adenocarcinoma HeLa cells.

■ Ukixanthomycin A: A Hexacyclic Xanthone from the Mudflat-Derived Actinomycete Streptomyces sp.

Yuhei Koyanagi, Teppei Kawahara, Yuki Hitora, and Sachiko Tsukamoto*

*Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan

Abstract

A new hexacyclic xanthone, ukixanthomycin A (1), was isolated from the mudflat-derived Streptomyces sp. HGMA004 by screening based on chemical analysis by UPLC-HRMS with our in-house actinomycete extract library. The structure of 1 was elucidated by spectral analyses and quantum chemical calculations. Compound 1 showed weak antifungal activity against Candida albicans.