HETEROCYCLES

■ Contents

■ Synthesis and Bioactivity of Pyrroloindazoles: An Overview

Manas Chakrabarty,* Moumita Rakshit, and Gandhi K Kar

*Department of Chemistry, Presidency University, 86/1, College Street, Kolkata-700073, India

Abstract

In this review, the synthesis and bioactivity of pyrroloindazoles have been presented. The pyrroloindazoles were synthesised either by the heteroannulation of tetrahydro-indolones/isoindolones, aminoindazoles, Sonogashira/Cacchi indazolic substrates or acyl/aroylindole ketoxime dinitrophenyl ethers or by the cycloaddition of indolynes, indazolic betaines, styrylpyrazoles and nitroindazoles. Several pyrroloindazoles showed analgesic, antiinflammatory and antitumor properties, inhibition of Pim kinase and soluble guanylate cyclase, and antagonism of NMDA-receptor.

■ Site-Selective Introduction of an Enamido Group at the C(3)-Position of Indoles

Tomoya Miura,* Qiang Zhao, Yuuta Funakoshi, and Masahiro Murakami*

*Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, youdai-katsura, Nishikyo, Kyoto 615-8510, Japan

Abstract

An enamido group is introduced site-selectively at the C(3)-position of indoles by the rhodium(II)-catalyzed reaction with N-sulfonyl-1,2,3-triazoles. Formally, an α-imino rhodium carbene complex is inserted into the C(3)-H bond of an indole.

■ NIR-Fluorescent Ethyl 4,7-Bis(5-arylthiophen-2-yl)-1,2,5-oxadiazolo[3,4-c]pyridine-6-carboxylate

Kentaro Nishi,* Nobuyuki Seto, Wataru Iwasaki, Yohei Matsuoka, Yuki Kashiwa, Youichi Sano, Tadashi Kawaharada, Takashi Yazumi, Keiji Mizuki, and Shin-ichiro Isobe

*Faculty of Engineering, Kyushu Sangyo University , 3-1 Matsukadai, 2-Chome, Higashiku, Fukuoka 813-8503, Japan

Abstract

Ethyl 4,7-bis(5-bromothiophen-2-yl)-1,2,5-oxadiazolo[3,4-c]pyridine-6-carboxylate 2 reacted with phenyl-, 4-methylphenyl-, 4-methoxyphenyl-, 3,4-dimethoxyphenyl-, 1-naphthyl-, and 2-naphthyl-boronic acid to give the corresponding π-extended 4,7-bis(5-arylthiophen-2-yl) derivatives 3a–f, which emitted fluorescence at around 700 nm in DMSO solution. The 4-methoxy and 2-naphthyl derivatives (3c and 3f) emitted fluorescence at 729 nm (13717 cm-1, Φ = 0.02) and 714 nm (14005 cm-1 and Φ = 0.11), respectively, with a large Stokes shift (184 and 182 nm for 3c; 4631 cm-1 and 4791 cm-1 for 3f).

■ Development of a Practical Synthesis of 7-Bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one

Kazuhiro Kudo,* Takahiro Honda, and Noriyoshi Yamamoto

*Product Supply Division, Santen Pharmaceutical Co., Ltd., 348-3, Aza Suwa Oaza Shide Taga-cho Inugami-gun Shiga, Japan

Abstract

Synthesis of 7-bromo-8-methoxycarbonyl-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one from 5-amino-2-bromobenzoic acid was achieved in an overall yield of 27% over four steps. This is a significant improvement from the previous six-step process, which afforded only a 12% yield. The previous process was optimized by adding a high-yielding alkylation step under mild conditions as well as by reducing the number of isolation steps and eliminating purification by column chromatography.

■ Crystal Structures of 2-Furylbenzimidazoles with Antiangiogenic Inhibition of VEGF in Cell Line MCF-7

Keith J. Flanagan, Yasser M. Shaker, Ahmed Temirak, Hoda I. El Diwani, and Mathias O. Senge*

*Medicinal Chemistry, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland

Abstract

The first crystal structures of four 2-furylbenzimidazole acetohydrazide derivatives are reported herein. The compounds have been shown to be planar with a small cant that varies from 4 to 30°. The X-ray crystal structure of the compounds 7-10 revealed that compounds are oriented in the cis configuration which suggests that the acid hydrazide group is essential for the enhanced potency of 2-furylbezimidazoles as anti-angiogenic agents.

■ Novel Grinding Synthesis of Pyranopyrazole Analogues and Their Evaluation as Antimicrobial Agents

Ashok Sharma, Badvel Pallavi, Rajnish Prakash Singh, Prabhat Nath Jha, and Paritosh Shukla*

*Department of Chemistry, Birla Institute of Technology and Science, BITS-Pilani, Pilani-333301, Rajasthan, 333031, India

Abstract

The paper describes the results of a new four-component synthesis of pyranopyrazole heterocycles by solvent-free one-pot grinding of malononitrile, hydrazine, ethyl acetoacetate, and various aldehydes in the presence of a base. The reaction proceeded smoothly at room temperature with good yields in very short reaction time. The synthesised compounds were evaluated for their in-vitro antibacterial activity against three different bacterial and three different fungal strains. The highlight of this work is that the synthesis was activity-driven. The brief SAR correlation found that the tested compounds showed better activity against fungal strains.

■ Synthesis of Phenylselanylisochroman-1-ones through Highly Selective Selenolactonization of Styrene-Typed Carboxylic Acids

Enshan Zhou,* Xin Han, Yuanyuan Li, Chao Guo, and Chune Dong*

*School of Pharmaceutical Sciences, Wuhan University, Hubei, Wuhan, 430071, China

Abstract

The novel synthesis of phenylselanylisochroman-1-ones was achieved by selenolactonization of styrene-typed carboxylic acids and phenylselenenyl chloride in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO). The reactions give excellent yields with high exo-selectivity.

■ Ga(III) Catalyzed Addition of Indole Derivatives and Different Propiolates

Xun Zhu,* Xiuqin Zhou, and Dongsheng Xiang

*Department of Chemistry, Yancheng Institute of Industry Technology, Yancheng, Jiangsu, 224005, China

Abstract

Ga(III) was used to catalyze Michael addition of indole derivatives to different propiolates in aqueous solution. Good to excellent yields were obtained under our reaction conditions.

■ Simple and Efficient Synthesis of Some Novel Triazoles Sulfonamides

Maha Hachicha, Monaem Balti,* Hédi Mrabet, and Mohamed Lotfi El Efrit

*Department of Chemistry, Faculty of Sciences of Tunis-Tunisia, El Manar-B.P. 94 Poste Romena, 1068, Tunisia

Abstract

Reaction of iminoesters 1 with sulfonyl isocyanates gave the corresponding sulphonamide imidates 2. The cyclocondensation of the latter with a series of hydrazine in methanol affords new functionalized triazoles in high yields.

■ Development of an Efficient Process for 3,6-Dihydro-2H-pyran-4-boronic Acid Pinacol Ester

Feng Xue,* Yong Zhu, and Chang-Gong Li

*Key Laboratory of Functional Organic Molecules of Xinxiang City Henan Province, College of Chemistry and Chemical Engineering, Henan Institute of Science and Technology, Xinxiang Henan, 453002, China

Abstract

An efficient process for the synthesis of 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester has been developed in one-pot manner. Starting from the condensation of 4-tetrahydropyranone with hydrazine hydrate, the subsequent treatment of hydrazone with copper(II) bromide-triethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) conveniently gave 4-bromo-3,6-dihydro-2H-pyran, which was then conducted through palladium-catalyzed borylation to afford the desired product using a low loading of a Pd catalyst.

■ Synthesis of 2-(Arylmethylene)-1,4-benzoxazin-3-one by One-Pot Sonogashira and 6-exo-Dig Cyclization

Dahye Lee, Sunhwa Park, Yosep Yu, Kye Jung Shin, and Jae Hong Seo*

*College of Pharmacy, The Catholic University of Korea, 43 Jinong-ro Wonmi-gu Bucheon, Gyeonggi-do, 420-743, Korea

Abstract

A novel, efficient one-pot approach to synthesize 2-(arylmethylene)-1,4-benzoxazin-3-ones has been developed. This method effectively combined the Sonogashira reaction of electron-deficient propiolamide and successive 6-exo-dig cyclization to selectively provide (Z)-isomers of 2-(arylmethylene)-1,4-benzoxazin-3-ones in good yield.

■ Preparation and Antibacterial Evaluation of Some Symmetrical Twin-Drug Type Bivalent Molecules

Fumiko Fujisaki, Makoto Furutachi, Ryou Fujiwara, Miriko Okabe, Hatsumi Aki, Nobuhiro Kashige, Fumio Miake, and Kunihiro Sumoto*

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

As one of our projects to investigate new bioactive compounds, we here report the synthesis and antibacterial evaluation of a few identical linker mode twin-drug type symmetrical hydantoin derivatives. The antibacterial activity of tested twin-drug type hydantoin derivatives (4~7) and the structure-activity relationships (SARs) of these bivalent symmetrical molecules are also described.