HETEROCYCLES

■ Contents

■ Syntheses of Heterocycles via Alkyne-Carbonyl Metathesis of Unactivated Alkynes

Akio Saito* and Keiichiro Tateishi

*Division of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan

Abstract

The formation of α,β-unsaturated carbonyl compounds by a catalytic alkyne-carbonyl metathesis, which can be catalyzed by both π- and σ-acids, has received attention as an atom economical process alternative to the Wittig reaction. During the last decade, the catalytic alkyne-carbonyl metathesis has provided attractive methods for the construction of various cyclic compounds. This review summarizes synthetic methods of heterocycles with a focus on recent advances in the catalytic alkyne-carbonyl metathesis of the unactivated alkynes.

■ Phase-Transfer Catalyzed Sulfenylation of 3-Substituted-2-oxindoles

Kazuhiro Nagata, Daisuke Sano, Osamu Aoyama, Takuya Kanemitsu, Michiko Miyazaki, Yuki Odanaka, Ayano Machida, and Takashi Itoh*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

Optically active 3-sulfenyl-2-oxindoles were synthesized by a catalytic asymmetric substitution with a chiral phase-transfer catalyst. The reaction was suggested to proceed in a radical mechanism.

■ An Efficient Synthesis of 1-(4H-1,2,4-Triazol-3-yl)-Hexahydroquinoline-3-carbonitrile and their Spiro Derivatives from β-Enaminones

S. A. Soliman Ghozlan, Doaa M. Abdelmoniem, Mohamed F. Mady, Amr M. Abdelmoniem, and Ismail A. Abdelhamid*

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

Abstract

A series of N-((1,2,4-triazol-3-yl)-enamine and N-((1,2,3-triazol-4-yl)-enamine were prepared and reacted with α,β-unsaturated nitriles yield novel N-(4H-1,2,4-triazol-3-yl)-hexahydroquinoline-3-carbonitrile and their fused and spiro derivatives. Dimroth type rearrangement of the prepared quinoline derivatives 7a,b and 15a,b was observed in acetic anhydride leading to the formation of substituted pyrimido[4,5-b]quinoline 11a,b, spiro[indoline-3,5'-pyrimido[4,5-b]quinoline] 19 and spiro[indoline-3,5'-[1,3]oxazino[4,5-b]quinoline] 22.

■ Synthesis of Some Novel Thiadiazoles and Thiazoles Linked to Pyrazole Ring

Magda A. Abdallah, Sobhi M. Gomha,* Mohamad R. Abdelaziz, and Nany S. Eldin Serag

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

Abstract

The novel compound namely ethyl 3-(1-(2-(2-cyanoacetyl)- hydrazono)ethyl)-1,5-diphenyl-1H-pyrazole-4-carboxylate 3 was used as key intermediate for synthesizing the thioanilide derivative 4 and the arylidene derivatives 6. The reaction of 4 with a number of haloketones and haloesters furnished the respective thiazole derivatives 8, 10 and 11a,b. Moreover, the reaction of 4 with N-aryl-2-oxopropane hydrazonoyl chloride 13 and ethyl (N-arylhydrazono)chloroacetate 17 in absolute ethanol in the presence of triethylamine at reflux afforded a new series of thiadiazoles 15 and 19, respectively. The mechanisms that account for formation of products 15 and 19 were discussed. Also, the structures of all the newly synthesized products were confirmed based on elemental analysis, spectral data and by alternative methods.

■ Synthesis and in vitro Antitumor Activity of 9-Hydroxyellipticine Derivatives with Glucose Conjugation via Triazolylmethyl Succinate Linker

Naoya Sato, Yu Kawai, Yosuke Akaba, Shoji Honma, Norio Sakai, and Takeo Konakahara*

*Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

Three types of novel 9-hydroxyellipticine derivatives 7a-c with glucose conjugation, linked by a triazolylmethyl succinic ester bond, were synthesized, and their cytotoxicity against HeLa S-3 and 293T cells was evaluated together with ellipticine (1) and 9-hydroxyellipticine (3). These new compounds 7a-c exhibited potent antitumor activity against HeLa S-3 and 293T, and water solubility of 7a was greatly higher than those of 1 and 3. The effects of an -OCH2CH2- spacer and the amino sugar moiety on the antitumor activity were examined using 7b,c. Furthermore, one of these glucose-conjugates 7a was applied to hydrolysis, catalyzed by carboxyesterase, leading to the formation of 3 under physiological conditions.

■ Antioxidant Activity of Ascorbic Acid Analogs Containing a Nitrogen Atom in the Ring

Shogo Nomura, Keiko Inami, and Masataka Mochizuki*

*Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan

Abstract

Ascorbic acid (AscH2) is a powerful antioxidant and protects the human body from oxidative stresses by scavenging reactive oxygen species. AscH2 analogs containing a carbonyl conjugated ene-diol structure and endocyclic nitrogen atom were evaluated for their oxidation potentials by cyclic and differential pulse voltammetry. The oxidation potentials of AscH2 analogs in which the endocyclic oxygen atom of AscH2 was replaced by a single nitrogen atom were lower than those of AscH2 under both non-aqueous and aqueous conditions. The results demonstrate that these analogs can have powerful antioxidant activities under physiological conditions.

■ Application of Mannich and Michael Reactions in Synthesis of Pyridopyrimido[2,1-b][1,3,5]thiadiazinones and Pyridopyrimido[2,1-b][1,3]thiazinones as Anticancer Agents

Sobhi M. Gomha,* Magda A. Abdallah, Mahmoud A. Mourad, and Mahmoud M. Elaasser

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

Abstract

A new series of pyrido[2',3':4,5]pyrimido[2,1-b][1,3,5]thiadiazinones were prepared by aminomethylation of pyridopyrimidinethione with a variety of primary aromatic amines and formaldehyde solution (37%) through Mannich reaction. Also, another series of pyrido[2',3:4,5]pyrimido[2,1-b][1,3]thiazinones were synthesized by Micheal addition reaction of pyridopyrimidinethione to the activated double bond of a number of arylidene malononitrile and ethyl 3-aryl-2-cyanopropenoate. The mechanism of formation of the synthesized compounds was discussed and the assigned structure was established via microanalysis and spectral data (IR, 1HNMR and Mass). In addition, the antitumor activities of the synthesized compounds were investigated in comparison with the well-known anticancer standard drugs doxorubcin and Imatinib using MTT assay. The results revealed that the tested compounds showed high variation in the inhibitory growth rates and activities against the tested tumor cell lines in a concentration dependent manner. The highest activity was measured for compound 4g against human hepatocellular carcinoma (HepG2) cells and compound 4i in case of breast carcinoma (MCF-7) cells compared with reference drug imatinib. These results revealed that these compounds exhibited promising antitumor activities.

■ A Simple Synthesis of Benzodiazonines from C-2 Arylated 1, 3-Indanediones

Suven Das* and Arpita Dutta

*Department of Chemistry, Rishi Bankim Chandra College for Women, East Kanthalpara, Naihati, India

Abstract

A simple, facile, one-pot procedure for the synthesis of substituted benzodiazonines from phenolic adducts of ninhydrin is described. The process involves a base-catalyzed rearrangement followed by condensation of 1,3-propanediamine to furnish nine-membered heterocyclic ring system.

■ A Novel Solid-Phase Synthesis of 2H-Chromenes

E Tang,* Yinjiao Zhao, Meng Zhang, Xin Dai, Weilin Wang, and Deshou Mao*

*School of Chemical Science and Technology, Yunnan University, No. 2 Green Lake North Road, Kunming 650091, China

Abstract

A method for synthesizing substituted 2H-chromenes using TMSOTf-catalyzed polystyrene-supported succinimidyl selenide-induced intramolecular seleno-arylation of tethered alkenes as a key step has been developed. The catalytic process provides an efficient method for the stereoselective and regioselective synthesis of 3,4-dihydro-2H-chromenes possessing a seleno-functionality, followed by syn-elimination of selenoxides to provide 2H-chromenes in good yields and with high purities.

■ Synthesis of a New Chiral C2-Symmetric NHC-AuCl Complex

Naoya Okitsu, Takuya Yoshida, Kensuke Usui, and Masahisa Nakada*

*Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

Abstract

A New chiral C2 symmetric NHC ligand with two binaphthyl units has been synthesized. The new NHC ligand features two seven-membered rings that link the imidazolylidene with the binaphthyl units. X-Ray crystallographic analysis of the new NHC-AuCl complex indicates that the Au-Cl bond is located between the phenyl groups of the binaphthyl units and suggests that this arrangement could induce enantioselectivity in reactions. Indeed, catalytic asymmetric ene-yne cyclization of 2b in the presence of a catalytic amount (5 mol%) of cationic complex of 13 quantitatively afforded the cyclized product with 78% ee.

■ A Facile One-Pot Synthesis of Benzo[b]benzofuro- and Benzo[b]benzothieno[3,2-h][1,6]naphthyridines

Dao-Lin Wang,* Ting Zhou, Jin-Juan Xing, Jian-Hua Qiang, and Lin Liu

*Liaoning Key Laboratory of Synthesis and Application of Functional Compound, College of Chemistry & Chemical Engineering, Bohai University, Jinzhou 121001, China

Abstract

An efficient domino protocol for the synthesis of benzo[b]benzofuro- and benzo[b]benzothieno[3,2-h][1,6]naphthyridines (5) was described. The construction of this new pentacyclic system was achieved undergo a tandem Thorpe-Ziegler-type heterocyclization of 3-acetyl-2-bromomethylquinolines (2) with salicylonitriles (3) or 2-mercaptobenzonitrile (4) in one-pot with good yields.

■ Design, Synthesis And Biological Activity Of Novel Sulfonylurea Oxazolidines

Ying Fu, Jing-Xin Kang, Yun-Kai Wang, Jing Liu, Li-Xia Zhao, Shuang Gao, and Fei Ye*

*Department of Applied Chemistry, College of Sciences, Northeast Agricultural University, No.59 Mucai Street Harbin 150030, Heilongjiang, China

Abstract

A series of N-[(p-methylphenyl)sulfonyl]-1,3-oxazolidine- 3-carboxamide 4 was synthesized by cycloaddition and acylation reaction with alkamine, ketones, and p-methylbenzenesulfonyl isocyanate as the starting materials. The structures of all the compounds were characterized by IR, 1H NMR, 13C NMR, MS, and elemental analysis. The configuration of 4d was determined by X-ray crystallography. The preliminary biological test showed that all compounds could protect maize against injury caused by chlorsulfuron to certain extent. The sulfonylurea oxazolidines were possible acted as antagonists of sulfonylureas herbicides at target enzyme pocket site by docking analysis.