HETEROCYCLES

■ Contents

■ Advances in the Synthesis of 1,2,4-Triazolo[1,5-a][1,3,5]triazines (5-Azapurines) and Their Biological Activity

Koon Kee Kow and Anton V. Dolzhenko*

*School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia

Abstract

The 1,2,4-triazolo[1,5-a][1,3,5]triazine system has been recognized as a promising scaffold for drug development purposes. The isosteric relationship between this skeleton and purines plays an important role in the research towards the development of bioactive 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives. This review discusses recently developed strategies for the synthesis of 1,2,4-triazolo[1,5-a][1,3,5]triazines and advances achieved in studies on biological activity of compounds constructed using this skeleton

■ Bis-Heterocycles. Part II. Tetrahydro-3,3'-bi(1,2,4,5-oxatriazines)

Mustafa M. El-Abadelah, Firas F. Awwadi, Monther S. Zreid, and Mohammed M. Abadleh*

*Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, University of Petra, Amman 11196, Jordan

Abstract

A new set of tetrahydro-3,3'-bi(1,2,4,5-oxatriazines) 3a-e has been prepared via condensation reaction of alkanone- and cycloalkanone N-methylhydrazones with bis-nitrile oxide. Structures of the synthesized bis-heterocycles are based on IR, NMR and MS spectral data and further confirmed by single-crystal X-ray diffraction analysis for compounds 3a and 3d. Compound 3c exhibited inhibitory activity against butyrylcholinesterase (BChE) with IC50 = 1.75 × 10-5 μM.

■ Efficient Synthesis of Chiral 5-Methoxycarbonylpyridin-2(1H)-ones and 3-Bromo-5-methoxycarbonylpyridin-2(1H)-ones

Hugo Pilotzi, Dino Gnecco,* María L. Orea,* David M. Aparicio, Sylvain Bernes, Jorge R. Juárez, and Joel L. Terán

*Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edif. IC9 Complejo de Ciencias, C.U., 72570 Puebla, Mexico

Abstract

Starting from the mixture methyl-(S)-3-(1-phenylethylamino)acrylate 1-(E,Z) and the mixture methyl (R)-3-(2-(tert-butyldimethylsilyl)oxy-1-phenylethyl)amino acrylate 2-(E,Z) were synthesized the corresponding chiral 5-carbomethoxy-pyridin-2(1H)-ones in high yield. Finally, starting from these chiral pyridin-2(1H)-ones were prepared the corresponding 3-bromo-5-carbomethoxy-pyridin-2(1H)-ones in high yield.

■ Synthesis, Crystal Structure, Spectroscopic and Computational Studies of 2-{1-[2-(1,3-Dimethyl-4-nitro-1H-pyrazol-5-yl)hydrazono]ethyl}pyridine

Ahmad S. Abushamleh,* Kayed A. Abu-Safieh,* Monther A. Khanfar, Khaleel I. Assaf, Bader A. Salameh, and Nisreen J. Alwahsh

*Department of Chemistry, Faculty of Science, Hashemite University, P.O. Box 330127 Zarqa, 13133, Jordan

Abstract

2-{1-[2-(1,3-Dimethyl-4-nitro-1H-pyrazol-5-yl)hydrazono]ethyl}- pyridine has been prepared from 5-hydrazino-1,3-dimethyl-4-nitro-1H-pyrazole and 2-acetylpyridine in an ethanolic solution. It crystallizes as an (E/Z) isomeric pair in the triclinic space group P-1 with the lattice parameters: a = 10.357(1) Å, b = 11.613(1) Å, c = 13.069(1) Å, α = 67.74(1)°, β = 70.77(1)°, γ = 67.92(1)°, volume = 1315.6(3) Å3, Z = 2. The isomeric pair (E/Z) is contained in the unit cell, where the N-H group is H-bonded to the pyridine nitrogen and to the oxygen of the nitro group in the Z-isomer and to the oxygen of the nitro group only in the E-isomer. NMR showed that the E-isomer is the major. DFT calculations were performed to further investigate the electronic properties of the synthesized compound.

■ Synthesis of 1-Methoxyindoles and Related Analogs of Pimprinine, (±)-Chelonin A and B, Based on 1-Hydroxyindole Chemistry

Kazuko Aoki, Yoshiyuki Nagahama, Katsuko Sugaya, Yuki Maeda, Haruhiko Sato, Kyoko Nakagawa (Goto), and Masanori Somei*

*Noto Marine Laboratory, Institute of Nature and Environmental Technology, Faculty of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, 56-7 Matsuhidai, Matsudo-shi, Chiba 270-2214, Japan

Abstract

The total synthesis of pimprinine, (±)-chelonin A and B, and their analogs are achieved based on 1-hydroxyindole chemistry.

■ Synthesis of Alkenyl Sulfones Containing Norbornene Moiety

Sambasivarao Kotha* and Rama Gunta

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

Abstract

Various cyclopropane containing alkenyl sulfone derivatives were synthesized starting with a readily available Diels–Alder adducts.

■ Synthetic Study of an Intermediates towards Paracentrone

Taiki Kaneyama, Kazumi Fujimaru, Mami Takemura, Kizuku Hasegawa, Masahiro Hamada, Takao Kishimoto, Daisuke Urabe, and Noriyuki Nakajima*

*Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398, Japan

Abstract

Paracentrone (1), the second naturally occurring C31-methyl ketone apocarotenoid from fucoxanthin (2), was first isolated from the sea urchin Paracentrotus lividus. In this study, we focused on this carotenoid metabolite and report on a synthetic approach towards (3E)-(5R)-[(2R,4S)-2-hydroxyl-4-(tert-butyldimethylsilyl)oxy-2,6,6-trimethylcyclohexylidene]-1-iodo-4-methyl-1,3,5-hexatriene (5), a synthetic intermediate towards 1. This was obtained from epoxy acetylene (11) via (2E)-(4R)-[(2R,4S)-2-hydroxyl-4-(tert-butyldimethylsilyl)oxy-2,6,6-trimethylcyclohexylidene]-3-methylpenta-2,4-diene-1-ol (7).

■ Synthesis of 2-Substituted Indole with Hantzsch Ester Catalyzed by Palladium

Yanan Li,* Bo Wang, and Ruiguang Xing*

*School of Materials and Metallurgy, Inner Mongolia University of Science and Technology, No.7 Arding Street, Kun District, Baotou 014010, China

Abstract

An efficient reductive cyclization of o-nitrobenzyl ketone compounds was achieved by using a Hantzsch 1,4-dihydropyridine ester as a biomimetic reducing agent in the presence of catalytic palladium on carbon. 2-Substituted indoles were obtained in good yields. Investigation of the mechanism suggests that palladium hydride promotes the reduction of nitro group, and acetic acid was beneficial for the loss of water to produce the intended product. This reaction system can not only broaden the use of Hantzsch 1,4-dihydropyridine ester, but it also provides a novel approach for preparing indole compounds.

■ Site-Selective Acylation of Carbohydrates Directed by Recyclable Polymer-Supported Isothiourea Catalysts

Wang-Ze Song,* Kun Dong, Ming Li, Jun-Hao Li, Karim Ullah, and Yu-Bin Zheng*

*School of Pharmaceutical Science and Technology, Dalian University of Technology, No.2 Linggong Road, Ganjingzi District, Dalian City, Liaoning Province 116024, China

Abstract

The polystyrene-supported isothiourea catalysts, derived from the homogeneous catalyst BTMs, were synthesized and applied to the site-selective acylation of carbohydrates. The catalysts can be recovered and reused conveniently for 10 cycles without significantly loss in either activity or selectivity. It offers a sustainable and environmentally benign approach for the site-selective functionalization of carbohydrates.