HETEROCYCLES

■ Contents

■ Syntheses of Triazoloquinoxalines

Mohammed A. Baashen, Bakr F. Abdel-Wahab,* and Gamal A. El-Hiti*

*Applied Organic Chemistry Department, National Research Center, Dokki 12622, Giza, Egypt

Abstract

This review summarizes the synthetic procedures for the production of various types of triazoloquinoxaline derivatives. Synthesis of triazolo[1,5-a]-, triazolo[4,3-a]-, triazolo[4,5-g]- and bis-triazoloquinoxalines are given. The main synthetic methods involve diazotization of 2-nitroanilines, then reaction with acid chloride derivatives followed by reduction of nitro groups and ring closure; ring closure of N-(2-alkynyl)-2-azido-anilines; reaction of 2,3-dichloroquinoxalines with acid hydrazides, or hydrazine hydrates and carbonyl compounds and reaction of 1,2-diaminobenzenes with hydrazonoyl halides. Triazoloquinoxalines are important intermediates for the design of novel biologically active molecules.

■ An Organocatalytic Asymmetric Diels-Alder Strategy for the Enantioselective Synthesis of Spirocyclic Oxindole-Cyclohexenones

Aoi Matsugi, Shiori Nunokawa, Naruhisa Watanabe, Yuya Nakata, Keiji Nakano, Yoshiyasu Ichikawa, and Hiyoshizo Kotsuki*

*Laboratory of Natural Products Chemistry, Faculty of Science, Kochi University, 2-5-1, Akebono-cho, Kochi 780-8520, Japan

Abstract

An efficient method for the asymmetric synthesis of spirocyclic oxindole-cyclohexenone conjugates was developed. A chiral thiourea-catalyzed asymmetric Diels-Alder reaction between 3-alkylidene-oxindoles and Rawal’s diene was used as the key strategy for construction of the desired products in moderate to good yields with good diastereo- and enantioselectivities.

■ Synthesis of Some Isoxazolidine and Isoxazoline Derivatives Using Nitrone-Derived (‒)-Menthone via 1,3-Dipolar Cycloaddition with Alkenes, Alkynes and Cycloalkenes

Heithem Abda, Kaïss Aouadi,* Moncef Mssadek, and Sébastien Vidal*

*Department of Chemistry, Faculté des Sciences de Monastir, Av de l'environnement 5019, Tunisia

Abstract

Cycloaddition reactions between a menthone-based chiral nitrone and alkenes or alkynes under microwave activation afforded a series of enantiopure cycloadducts in good yields and with high stereoselectivity. Removal of the chiral auxiliary under acid-catalysis led to a new series of isoxazolidines and isoxazolines with the control of one, two or three stereogenic centers.

■ Structure-Activity Relationship of Phenylethanoid Glycosides on the Inhibition of Amyloid β Aggregation

Eri Kidachi, Manami Kurisu, Yusaku Miyamae, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, and Hideyuki Shigemori*

*Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Japan

Abstract

The structure-activity relationship of the inhibitory activity of Aβ aggregation and antioxidant activity for phenylethanoid glycosides, acteoside (1), oraposide (2), and their derivatives which isolated from Orobanche minor was investigated. Acteoside (1) and oraposide (2) containing two catechol moieties exhibit strong activities for inhibition of Aβ aggregation and antioxidant. These results suggested that existence of the catechol moieties of the phenylethanoid glycosides were important roles for these activities.

■ A Concise and Highly Efficient Synthesis of Praziquantel as an Anthelmintic Drug

Zhezhou Yang, Lin Zhang, Huirong Jiao, Rusheng Bao, Weiwei Xu, and Fuli Zhang*

*Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, China

Abstract

A concise and practical synthesis of praziquantel as anthelmintic drug is described. The key steps include a monoalkylation of ethanolamine for the preparation of 2-(2-hydroxyethylamino)-N-phenethylacetamide and a mild oxidation protocol with SO3-Py/DMSO as oxidant to transform alcohol into the corresponding aza-acetal. The telescoped synthesis is composed of five steps without purification of the intermediates, providing an overall yield of 80% with 99.8% purity after crystallization.

■ Intermolecular Hydroamination of Styrene Catalyzed by Palladium(II) N-Heterocyclic Carbene Complexes in Ionic Liquid

Beyhan Yiğit, Murat Yiğit,* Yetkin Gök, and Özlem Özeroğlu Çelikal

*Department of Chemistry, Faculty of Science and Art, Adıyaman University, 02040 Adıyaman, Turkey

Abstract

PdCl2(NHC)2 complexes have been synthesized by the reaction of palladium acetate with a series of benzimidazolium and imidazolinium salts and characterized by elemental analysis, 1H NMR and 13C NMR spectroscopy. These complexes were used as catalysts for the intermolecular hydroamination reactions between styrene with various anilines in ionic liquid at 160 oC and corresponding anti-Markovnikov products were obtained with a selectivity of 100% in good yields.

■ Synthesis of New 3-Substituted 1-Hydroxy-2-phenylindoles Using Sulfur-Containing Nucleophiles

Hyejin Kim and Sang Hyup Lee*

*College of Pharmacy and Innovative Drug Center, Duksung Women's University, Seoul 01369, Korea

Abstract

The synthesis of new 3-[(acyl(or alkyl)thio)methyl]-1-hydroxy-2- phenylindoles 1 are presented. The substrates 2 obtained by each efficient three-step synthesis were treated, in the presence of SnCl2·2H2O, with nucleophiles such as thiocarboxylic acids and thiols to provide target compounds 1 by successive processes of nitro reduction and intramolecular condensation, followed by addition of nucleophile. Analyses of the reaction mechanism, including the effects of substituents along with the reactivity of nucleophiles, are described.

■ Synthesis and Evaluation of the Antitumor Activities of Two Series of Jaspine B Analogues Bearing 2-Alkyloxymethyl Group

En Zhang,* Shang Wang, Jie Gao, Xiao-Jing Shi, Ming-Ming Wang, Shuai-Min Xu, and Hong-Min Liu*

*School of Pharmaceutical Sciences, Zhengzhou University, Ke xue DaDao 100, Zhengzhou 450001, China

Abstract

Two series of jaspine B analogues bearing 2-alkyloxymethyl group have been synthesized and evaluated for their cytotoxicity against four cancer cell lines, including Eca-109, EC-9706, B16-F10 and MCF-7 cells. Most of the compounds exhibited potent cytotoxic activity against all four cell lines. The results also revealed that some of the analogues prepared in the current study exhibited comparable or better in vitro antitumor activity to jaspine B. Compound 9g, in particular, displayed the most potent antitumor activity of all of the compounds prepared in the current study with an IC50 value of 2.0 ± 0.4 μM towards B16-F10 cells, which was better than that of jaspine B (IC50 = 5.08 ± 0.6 μM). The results of a structure–activity relationship study showed that the oxygen atom and the length of the alkyl chain have an effect on the cytotoxic activity of these compounds.

■ Titanium Tetraiodide Induced Cyclization of Cyanoketones into 3-Aryl-1-iodoisoquinolines

Kai Yashiro, Keito Sakata, Iwao Hachiya, and Makoto Shimizu*

*Department of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Kurimamachiya-cho Tsu, Mie 514-8507, Japan

Abstract

3-Aryl-1-iodoisoquinoline synthesis is developed using titanium tetraiodide induced cyclization of cyanoketones. The method is applied to the short step formal synthesis of CWJ-a-5 having a topoisomerase I inhibitory activity. 3-Iodo-1-phenylisoquinoline synthesis is also reported under the similar reaction conditions.

■ Facile Synthesis of Imidazo[1,5-a]pyrazin-8(7H)-ones from Mesoionic 1,3-Oxazolium-5-olates via a Multistep One-Pot Transformation

Ryosuke Saijo, Hidemitsu Uno, and Masami Kawase*

*Faculty of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan

Abstract

A novel one-pot conversion of mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates into imidazo[1,5-a]pyrazin-8(7H)-ones by the reaction with TosMIC is described. The structure of the product was determined by single-crystal X-ray analysis.

■ Two New Atisine-Type C20-Diterpenoid Alkaloids from Aconitum leucostomum

Wenliang Xu, Lin Chen, Lianhai Shan, Feng Gao, Shuai Huang, and Xianli Zhou*

*School of Life Science and Engineering, Southwest Jiaotong University, NO.111, North Second Ring Road Chengdu 610031, Sichuan, China

Abstract

Two new atisine-type C20-diterpenoid alkaloids, leucostomine A (1) and leucostomine B (2) were isolated from the root of Aconitum leucostomum. Their structures were determined by spectroscopic methods including 1D-, 2D-NMR, and HR-ESI–MS.

■ A Simplified Green Chemistry Approach to Synthesis of Azolo[1,5-a]pyrimidine Incorporated Thiophene Moiety

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

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

Abstract

A highly efficient and environmentally friendly protocol has been developed for a facile synthesis of novel azolo[1,5-a]pyrimidines incorporated thiophene moiety under microwave irradiation. The advantages of short reaction time, high efficiency, no separation of in situ generated intermediate, using cheap, non-corrosive sodium persulfate as the oxidant, together with a very simple work-up procedure, make this one-pot and solvent-free protocol a green and powerful alternative to traditional methods for the synthesis of these kinds of compounds.