HETEROCYCLES

■ Contents

■ Synthesis of the Aglycon of Pentalinonside

Nobuhisa Isaka, Saki Kawada, Masaji Ishiguro,* and Minoru Tamiya*

*Chemical Biology Laboratory, Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1, Higashijima, Niigata 956-8603, Japan

Abstract

The aglycon of pentalinonside (2), a novel seco-pregnane with cage-like DEF-rings, was synthesized. Polyoxygenated DEF-rings were constructed using a known 14,20(16),21(15)-triol derivative via 5-exo-cyclization for the F-ring annulation, followed by C14–21(15) oxidative cleavage and intramolecular acetalization.

■ Metal-Free Synthesis of Benzothiazoles from Disulfides of 2-Aminobenzenethiol and Carboxylic Acid via PCl3-Promoted Tandem Reaction

Guangyan Du, Ning Zhu,* Limin Han, Hailong Hong, and Quanling Suo

*Chemical Engineering College, Inner Mongolia University of Technology, Hohhot 010051, China

Abstract

A metal-free process for the synthesis of benzothiazoles via PCl3-promoted cleavage/acylation/ cyclization of disulfides and carboxylic acids has been developed. In addition to acting as the acylating reagent which converted carboxylic acids into acyl chlorides, PCl3 also converted disulfides to thiols, which promoted disulfides of 2-aminobenzenethiol reacted with carboxylic acid to produce benzothiazoles. The developed method is applicable to a wide range of carboxylic acids containing different functional groups.

■ Synthesis and in vitro Cytotoxicity Evaluation of New 2-Thioxo-benzo[g]quinazolin-4(3H)-one Derivatives

Rashad Al-Salahi,* Rabab A. El Dib, and Mohamed Marzouk*

*Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh-11451, Saudi Arabia

Abstract

Preparation of the titled 2-thioxo-benzo[g]quinazolin-4(3H)-ones (1–4)　has been previously reported. In the present study, compounds (1–4) were elaborated in high and quantitative yields by simple modification on the reported synthetic route. Treatment of 2-thioxo-benzo[g]quinazolin-4(3H)-ones (1–4) with hydrazine hydrate or with different alkyl(heteroalkyl) halides afforded smoothly the target products 5, 6 or 7–28 in good and high yields. The in vitro cytotoxicity of compounds 1–28 was evaluated against colon HCT-116, hepatocellular Hep-G2, and breast MCF-7, prostate PC-3 and lung A-549 cancer cell lines, using MTT assay. The IC50-values of the target compounds are recorded in µg/mL and doxorubicin used as a reference drug. The results revealed that compounds 1, 3, 7, 10, 13, 14, 15, 16, 20, 21 and 22 had significant cytotoxic effects in relation to the reference drug. The structures of compounds 1–28 were elucidated by means of 1H- and 13C-NMR and HREI mass spectrometry.

■ The Synthetic Studies of Carbazole Alkaloids

Hajime Yokoyama,* Yuzen Shoji, Takayoshi Kubo, Masahiro Miyazawa, and Yoshiro Hirai

*Department of Chemistry, Graduate School of Science and Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

The carbazole alkaloids have profound biological activities and material properties. We reported that 3, 4-substituted, 3-substituted and 4-substituted carbazoles were regioselectively synthesized from indoline derivatives by means of Diels-Alder reaction in the presence or absence of Pd catalyst and attained the synthesis of natural carbazole alkaloid from 3-substituted carbazole, too.

■ Synthesis and Antihypertensive α-Blocking Activity Evaluation of Thiazole Derivatives Bearing Pyrazole Moiety

Sobhi M. Gomha,* Khaled Khalil, Hassan Abdel-aziz, and Mohamed Abdalla

*Department of Organic Chemistry, Cairo University, Giza-Haram 12613, Egypt

Abstract

A novel, facile reaction for the synthesis of series of thiazole derivatives has been developed from the reaction of the appropriate thiosemicarbazone derivatives and 2-bromo-1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethanone in ethanol under reflux. The structures of the newly synthesized products were established on the basis of spectral data (mass, IR, 1H and 13C NMR) and elemental analyses. The pharmacological screening showed that many of the synthesized compounds exhibit a good antihypertensive α-blocking activity and having low toxicity, as compared to Minoxidil.

■ Phenylpropanoids from the Leaves of Nicotiana tabacum and Their Anti-Tobacco Mosaic Virus Activities

Qin-Peng Shen, Lan Li, Xin-Meg Xu, Chun-Bo Liu, Neng-Jun Xiang, Feng-Mei Zhang, Pei He, Zhi-Hua Liu, Shan-Zhai Shang, Ming-Ming Miao,* and Guang-Yu Yang*

*Key Laboratory of Tobacco Chemistry of Yunnan Province, China Tobacco Yunnan Industry Company, Hongjin Road 181#, Kunming, 650231, China

Abstract

Two new phenylpropanoids, 5-hydroxy-6-(3-hydroxypropanoyl)- isobenzofuran-1(3H)-one (1), 6-(3-hydroxypropanoyl)-5-methylisobenzofuran- 1(3H)-one (2), together with four known phenylpropanoids (3-6) were isolated from the leaves of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-5 were tested for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that Compound 2 showed high anti-TMV activity with inhibition rate of 29.2%. This rate is close to that of positive control. The other compounds also showed potential anti-TMV activity with inhibition rates in the ranges of 20.3-24.6%, respectively.

■ Regioselective Synthesis of Pyrazoles and Pyrazolo[1,5-a]Pyrimidines: Structural Characterization by HMBC NMR

Abdullah S. Al-Bogami and Tamer S. Saleh*

*Department of Green Chemistry, National Research Centre, El-Tahrir Street, Dokki, Giza 12622, Egypt

Abstract

In this study a series of novel pyrazoles and pyrazolo[1,5-a]pyrimidines with a sulfone moiety incorporated the coumarin ring were efficiently synthesized. These pyrazoles and pyrazolo[1,5-a]pyrimidines were synthesized by treating enaminone derivative of β-ketosulfone (3-(2-tosylacetyl)-2H-coumarin) with substituted hydrazines and 5-aminopyrazole derivatives, respectively under microwave irradiation. The structures of the products thus obtained were characterized by 2D NMR (HMBC).

■ Synthesis and Characterization of Polysubstituted 5-Quinolinecarbaldehyde Derivatives

Nguyen Huu Dinh,* Duong Quoc Hoan, Nguyen Hien, and Tran Thi Thu Trang

*Department of Chemistry, Hanoi National University of Education, 136 Xuanthuy Hanoi, Vietnam

Abstract

A new quinolinecarbaldehyde, 7-(carboxymethoxy)-6-hydroxy-3-sulfo- quinoline-5-carbaldehyde (1), was synthesized from eugenol, a natural phenol, by four successive reaction steps. The condensation of 1 with various amino compounds afforded 12 Schiff-bases (2 – 13) and 3 hydrazones (14 – 16). The structures of the aldehyde, its Schiff-bases and the hydrazone derivatives were determined by analyzing their IR, 1D NMR, 2D NMR and MS spectra. 1H NMR and NOESY data show that the imine -CH=N- group in the reported Schiff-bases and hydrazones exists in E-configuration.

■ Viridobrunnines A and B, Antimicrobial Phenoxazinone Alkaloids from A Soil Associated Streptomyces sp.

Xiu Mei Zhang, Xu Liu, Zhe Wang, Zhen Hua Tian, and Wei Dong Xie*

*Department of Pharmacy, Marine College, Shangdong University at Weihai, Wenhua Xilu 180, Weihai 264209, China

Abstract

Chemical investigation of a Streptomyces sp. strain designated A1302 isolated from soil sample led to the discovery of two new phenoxazinone alkaloids, viridobrunnines A and B (1 - 2), along with two known analogues exfoliazone (3) and chandrananimycin D (4). Their structures were established by means of spectroscopic methods. The antibacterial and antifungal activity of isolated compounds was assayed. Viridobrunnine B (2) exhibited potent antibacterial activity against Bacillus subtilis with inhibition zone from 13 mm to 15 mm.

■ Flavones from the Leaves of Yunnan Local Sun Cured Tobacco and Their Cytotoxicity

Yu-Ping Wu, Guang-Hui Kong, Wei Li, Neng-Jun Xiang, Li-Xuang Liu, Guo-Rong Yang, Xiu-Ping Lu,* and Qiang Liu*

*Yunnan Academy of Tobacco Agricultural Sciences, Kunming, Yunnan 650031, China

Abstract

Two new flavones, 4',7-dimethoxy-6-hydroxy-8-isobutyrylflavone (1), 4',7-dimethoxy-6-hydroxy-8-[(E)-3-hydroxy-2-methylprop-1-enyl]flavone (2), together with four known flavones (3-6) were isolated from the leaves of Yunnan local sun cured tobacco. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-6 were screened for the cytotoxic activity in a panel of human cancer cell lines, including NB4, A549, SHSY5Y, PC3, and MCF7. Compound 2 exhibited high cytotoxicity for A549 and SHSY5Y cells with IC50 values of 1.6 and 2.8 μM, respectively. The other compounds also exhibited cytotoxicity with IC50 values in the range of 4.3 – 9.5 μM, respectively.

■ Design, Synthesis, and Evaluation of Novel 2-Halogenated or Aminated Carbocyclic Oxetanocin a Analogs as Potential Angiogenic Agents

Norikazu Sakakibara,* Junsuke Igarashi, Maki Takata, Ryoji Konishi, Natsuki Suzue, Yoshihisa Kato, Tokumi Maruyama, and Ikuko Tsukamoto

*Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki City, Kagawa 769-2193, Japan

Abstract

We succeeded in the synthesis of four types of carbocyclic oxetanocin A (2-Chloro-C.OXT-A; COA-Cl) analog: 2-halogenated or aminated carbocyclic oxetanocin A: COA-F, COA-Br, COA-I, and COA-NH2, which were synthesized and evaluated using human umbilical vein endothelial cells. Among these compounds, 100 M COA-Br and COA-I had greater angiogenic activity, with relative tube areas of 2.10 0.32 and 2.01 0.61 (mean SD), respectively, which were comparable to that of COA-Cl (2.30 0.59).