HETEROCYCLES

■ Contents

■ Sphingolipids and Glycosphingolipids — Their Synthesis and Bioactivities

Kenji Mori* and Takuya Tashiro

*Glycosphinogolipid Synthesis Group, Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Wako-shi, Saitama 351-0198, Japan

Abstract

Chemistry of sphingolipids and glycosphingolipids is discussed with main emphasis on their synthetic methods. Microbial, plant, animal and marine sphingolipids and glycosphingolipids with the following biological roles are treated in this review: (i) inducers of fruiting body formation in Basidiomycetes, (ii) water barrier and supporting material of animal epidermis, and (iii) bioregulators of medicinal interests including immunostimulants.

■ Synthesis of Various Substituted Spiro- and Bicyclethiazolidine-2-thiones by a Multicomponent Reaction and Biological Evaluation in vitro

Xiao-Juan Wang, Hai-Wei Xu, Lin-Lin Guo, En Zhang, Guang-Wei Chen, Xiao Guo, and Hong-Min Liu*

*New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450002, China

Abstract

A series of novel spiro[4.4] and bicycle[3.3.0]-N-substituted thiazolidine-2-thiones were obtained by a multicomponent reaction under mild conditions. Each of the synthesized compounds was evaluated for their cytotoxic activity and antibacterial activity. Some of them exhibited significantly inhibited proliferation of human tumor cell lines and moderate inhibitory effect on fungi.

■ Unexpected Formation of Thiino[3’,4’:4,5]oxazolo[1,3-b][1,3]oxazepine Derivatives

Akikazu Kakehi,* Kennosuke Itoh, Hiroyuki Suga, Hirofumi Kobayashi, Hideyuki Muranaka, and Motoo Shiro

*Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan

Abstract

The reactions of pyridinium 2-alkylthio-1-benzoyl-2-thioxoethylides with dimethyl acetylenedicarboxyate in THF at the reflux temperature afforded the unexpected products, dimethyl 2-alkylthio-4a-phenyl-4aH,5aH-thiino[3’,4’:4,5]oxazolo[1,3-b][1,3]oxazepine-3,4-dicarboxylates, together with dimethyl 10aH-4-alkylthio-5-benzoylpyrido[1,2-d][1,4]thiazepine-1,2- dicarboxylates.

■ A Facile Synthesis of 2,5-Disubstituted Indole Derivatives as New Fluorescent Dyes

Hidetaka Hiyoshi, Jung-Hee Do, Xing Feng, Taisuke Matsumoto, and Takehiko Yamato*

*Department of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga 840-8502, Japan

Abstract

A novel bis-arylated indole derivative, 2,5-bis(2-naphthyl)-1-methyl-1H-indole, was prepared and characterized. This compound shows the highly pure blue emissions both in solution and solid state which were ascribed to the expanded π-conjugation by introduction of two 2-naphthyl groups at the 2 and 5 positions on the indole ring. From X-ray crystallographic results this molecule exhibited the intermolecular CH–π interactions which consisted two dimensional (2D) herringbone structure.

■ Synthesis, Theoretical Study, and Antimicrobial Activity of Novel Polysubstituted Thiazoles

Nadia Hanafy Metwally* and Sabry El-Taher

*Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Abstract

New 5-(9H-Fluoren-9-ylidene)- and 5-(1H-indan-1-ylidene)-2-thioxo-4-thiazolidinones 3a,b were synthesized Eco-friendly under microwave irradiation (MWI). These compounds undergo alkaline hydrolysis to afford the corresponding thiol derivatives 4a,b, which cyclized into polysubstituted thiazoles 6a-h using arylazomalononitriles 5a-d as nucleophilic agents. Some selected products were tested for their antimicrobial activities. The equilibrium geometries of the studied compounds were calculated at the B3LYP/6-31G(d) level of the density functional theory (DFT). Conformational analysis has been carried out to determine the most stable conformers. The relative stability of the azo and hydrazo tautomers has been investigated. The HOMO-LUMO energy gap is used in rationalizing the reactivity of the studied compounds.

■ Synthesis, Crystal Structure and Antibacterial Evaluation of N-Substituted Perhydro-1,3-oxazin-2-ones Containing N-Phenylsulfonamide

Mounir Nessaib, Abdelghani Djahoudi, Achour Seridi, Hocine Akkari, Nour-Eddine Aouf, Jean-Claude Daran, and Mohamed Abdaoui*

*Laboratory of Applied Chemistry, University of May 8th, 1945, BP 401, Guelma, Algeria

Abstract

The synthesis of a new series of N-substituted perhydro-1,3-oxazin-2-ones containing N-phenylsulfonamide is described. The compounds 7a–7f were obtained in a one-pot reaction from chlorosulfonyl isocyanate, selected 1,3- halogenoalcohols and various aromatic amines in alkaline conditions, to give the target N-heterocyclic 6-membered ring compounds with good yields. The X-ray crystal structure of N-[(N-4-fluorophenyl)sulfamoyl]perhydro-1,3-oxazin-2-one 7d was solved. All the synthesized compounds have been screened for their in-vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Structures of 7d and 6e can be further optimized to give new potent antibacterial agents with structures significantly different from those of existing classes of antibiotics.

■ Synthesis and Mesomorphic Properties of a Series of Phenyl 6-(4-Alkoxyphenyl)nicotinates

Win-Long Chia* and Cheng-Yao Tsai

*Department of Chemistry, Fu Jen Catholic University, Taipei, Taiwan 24205, Taiwan, R.O.C.

Abstract

A new homologous series of phenyl 6-(4-alkoxyphenyl)nicotinates (nOPNicP, n = 3-7) was synthesized. The entire synthetic procedure was completed in a short two-step process. Very good two-step overall yields of 70-80% were obtained and high α–regioselective addition of Grignard reagents to 1-acylnicotinium salts was observed while preparing this series of liquid crystals. Spectral analyses were in accordance with the expected structures. Their thermotropic behaviours were studied using polarizing optical microscopy and further confirmed by differential scanning calorimetry. Smectic A phase was found to be the only mesophase in this series of compounds.

■ New Antibacterial Polyacetylenes from Sunflower (Helianthus annuus L.) Seedlings

Fumie Seshimoto, Si Won Hong, Haruyuki Nakajyo, and Hideyuki Shigemori*

*Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

Abstract

Three new C15 polyacetylenes 1, 2, and 3, together with two known C15 polyacetylenes 4 and 5 were isolated from the seedlings of sunflower Helianthus annuus L. cv Russia, and their structures were elucidated by spectroscopic data and chemical means. Compounds 1, 2, 4, and 5 exhibited antimicrobial activity against Staphyrococcus aureus and especially compound 1 showed strong activity.

■ Xanthones in Heterocyclic Synthesis. An Efficient Route for the Synthesis of C-3 o-Hydroxyaryl Substituted 1,2-Benzisoxazoles and Their N-Oxides, Potential Scaffolds for Angiotensin(II) Antagonist Hybrid Peptides

Yiannis Gardikis, Petros G. Tsoungas,* Constantinos Potamitis, Maria Zervou, and Paul Cordopatis*

*Research & Technology, Ministry of Education, 14-18 Messogeion Ave., Athens, GR-115 10, Greece

Abstract

Regioselective substitution of xanthone and its nucleophilic cleavage allow the synthesis of C-3 o-hydroxyaryl substituted 1,2-benzisoxazoles or their N-oxides by cyclodehydration or oxidative cyclization of their corresponding ketoxime precursors, respectively. Molecular modeling analysis and 1H NMR spectra indicate an intramolecular H-bonding engaging phenol OH and the isoxazole ring N atom.

■ Synthesis and Antitumor Activity of Novel N’-(2-Benzylthiobenzenesulfonyl)-1H-pyrazole-1-amidine Derivatives

Jarosław Sławiński,* Kamil Brożewicz, Andrzej Fruziński, and Marek L. Główka

*Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland

Abstract

A series of N´-(2-benzylthio-4-chlorobenzenesulfonyl)-1H- pyrazole-1-amidines (23-36) were synthesized by the reaction of 3-amino-2-(benzenesulfonyl)guanidines (18-22) with adequate 1,3-diketones. The compounds 23, 24, 26, 30, 31, 34 and 35 were tested in vitro in the full NCI 60 cell panel. The most potent compound in the series (26) showed substantial activity toward some cell lines of leukemia and cancer cells of lung, colon, CNS, melanoma, renal, prostate and breast (GI50 in the range 2.30-9.47 μM).

■ Simple Synthesis of Pratosine and Hippadine by Intramolecular Palladium-Catalyzed Cyclization and Decarboxylation

Hideaki Umemoto, Masashi Dohshita, Hiromi Hamamoto, and Yasuyoshi Miki*

*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan

Abstract

The palladium-catalyzed cyclization of dimethyl 1-(2-bromo-4,5-dimethoxybenzyl)indole-2,3-dicarboxylate in the presence of tetrakis(triphenylphosphine)palladium(0) and potassium acetate in hot 1,4-dioxane produced the 7H-pyrrolo[3,2,1-de]phenanthridine derivative, which was converted to pratosine by hydrolysis and decarboxylation. In a similar manner, hippadine was also prepared.

■ Microwave-Assisted Synthesis of 3,5-Disubstituted Thiohydantoins Using Functional Ionic Liquid as Soluble Support

Chen Zhuo,* Dong Xian, Xie Hui, and Li Mei

*School of Chemistry and Material Science, Guizhou Normal University, Guiyang, 550001, China

Abstract

A new approach for the syntheses of 3,5-disubstituted thiohydantoins was described using functionalized ionic liquid as soluble support. The products were obtained in good yields and purities after cyclization-cleavage from the ionic-liquid-supported under microwave irradiation, the ionic-liquid-supported species can there be purified from the reaction mixture by simple washing, and no chromatographic purification were needed during the synthesis.

■ Antifeedant Activities of Tutin and Andrographolide Derivatives against Mythimna separata

Jun Cui, Meng-Lou Li,* Yan-Bing Zhang, and Fei-Fei Li

*College of Forestry, Northwest A & F University, Yangling, Shaanxi, 712100, China

Abstract

Nine andrographolide derivatives (A2, A3a-b, A4a-e, A5) were synthesized to study the antifeedant activities of these derivatives and tutin against Mythimna separata. Compared with tutin, the nine derivatives exhibited better antifeedant activities, and six of them showed different mortality effects. It was concluded that the potent insecticidal agents are A2 (14-deoxy-11,12-didehydro-andrographolide), A4d (15-fluorobenzylidene-14-deoxy-11,12-didehydro-andrographolide) and A4e (15-bromoacylbenzylidene-14-deoxy-11,12-didehydro-andrographolide).

■ A New Depsidone from the Twigs of Garcinia cowa

Sarot Cheenpracha, Wong Phakhodee, Thunwadee Ritthiwigrom, Uma Prawat, and Surat Laphookhieo*

*Natural Products Research Laboratory, School of Science, Mae Fah Luang University, Tasud, Muang, Chiang Rai 57100, Thailand

Abstract

A new depsidone, cowadepsidone (7), along with six known xanthones (1-6) were isolated from the twigs of Garcinia cowa. Their structures were determined on the basis of spectroscopic methods. The cytotoxicity against KB, MCF-7 and NCI-H187 cancer cell lines of compounds 2-7 were also reported.

■ Feasible Synthesis of the GPR40 Antagonist by Constructing 2-Thiouracil Ring via Acid Mediated Cyclization

Yongfeng Zhao and Jiayu Liao*

*Department of Bioengineering, Bourns College of Engineering, University of California at Riverside, 900 University Avenue, Riverside, CA 92521, U.S.A.

Abstract

GW1100 is an antagonist of GPR40 identified by high throughput screening recently. The feasible synthesis of GW1100 has been developed in mild conditions. The key step involves the cyclization of the 2-thiouracil heterocycle under acidic conditions at room temperature.