HETEROCYCLES

■ Contents

■ Chemotherapeutic Potential of Acridine Analogs: An Ample Review

Harminder Singh, Harbinder Singh, Sahil Sharma,* and Preet Mohinder Singh Bedi

*Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India

Abstract

Acridine, a novel and pharmacologically important nitrogen containing heterocyclic ring exhibits a variety of potential biological activities. Among the reported therapeutic attributes of acridines, anticancer and antimicrobial are the most comprehensively studied ones. This fused heterocyclic ring has been evidenced in a number of research papers and patents. The principal target of these agents being nucleic acids, to which they bind reversibly by intercalation. This review article is merely an assemblage of all the patents and research work that has been done so far in the recent past on various acridine analogs as chemotherapeutic (anticancer and antimicrobial) agents. The promising activity revealed by these compounds chains their use and places them ahead as reasonably potential drug candidates for the upcoming studies. The present article can be reasonably constructive for those engrossed in the area of hunt for new and effective antimicrobial and anticancer compounds involving acridine as a crucial and central nucleus.

■ Microwave Assisted Synthesis of Disubstituted Imidazo[1,2-a]pyridine-3-carboxylic Acid Esters

Lin-hu Li, Zhao-yang Wu, Zhuo-rong Li, Ming-liang Liu,* Hui-yuan Guo, and Qiu-rong Zhang*

*Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China

Abstract

A novel and efficient synthetic method leveraging microwave-assisted organic synthesis (MAOS) to prepare disubstituted imidazo[1,2-a]- pyridine-3-carboxylic acid esters (IPCEs) (3a-z), the key intermediates for a class of novel anti-tuberculosis agents, is reported. Under microwave heating at 120 °C for 20 or 30 min, the condensations of 2-aminopyridines (1a-k) and ethyl 2-halogenated acetoacetates (2a-d) were conveniently performed in ethanol with acceptable yields.

■ Synthesis and Transformations of 2-Oxo-2,3-dihydro-(1H,3H)-quino[4,3-e]-1,2,4-thiadiazine 4,4-Dioxide to N-Methyl-, 2-Chloro- and 2-Aminoquino[4,3-e]-1,2,4-thiadiazine 4,4-Dioxides

Elwira Chrobak,* Stanisław Boryczka, Michał Wlekliński, Joachim Kusz, Maciej Zubko, and Andrzej Maślankiewicz

*Department of Organic Chemistry, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland

Abstract

Fusion of 4-amino-3-quinolinesulfonamide (1a) with urea and N-methyl- and N,N’-dimethylurea resulted in 2-oxo-2,3-dihydro-(1H,3H)- quino[4,3-e]-1,2,4-thiadiazine 4,4-oxide (3a). Reaction of thiadiazinone 3a with a MeI/MeOK/DMF system gave a mixture of the 3-methyl derivative 3c (major product) and 6-methyl derivative 3d (minor product), and the mixture of 3c and 3d could be methylated with the same system as above to afford the 3,6-dimethyl derivative 3e. Chlorination of 3a with P(O)Cl3/phosphoric acid system performed in the presence of pyridine hydrochloride resulted in zwitterionic pyridinio-quinothiadiazinate 7 (63%) accompanied by 2-chloroquinothiadiazine 6 (15%), and the same reaction performed with the use of triethylamine hydrochloride gave the expected chloroquinothiadiazine 6 (73%). Chloro derivative 6 was then aminated to 2-aminoquinothiadiazines 8a,b,c.

■ Expedient Synthesis of Novel Glycosyl Thiazole Derivatives

Feng-chang Cheng, Long Yin, Wei-wei Liu,* Qu-xiang Li, Li-juan Tang, Da-hua Shi, and Zhi-ling Cao

*School of Chemical Engineering, Huaihai Institute of Technology, Lianyungang City, Jiangsu Province 222005, China

Abstract

An efficient protocol for the synthesis of novel glycosyl thiazole derivatives starting from the commercially available D-glucosamine hydrochloride was described by reaction of 1-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranos-2-yl)thiourea 8 with each of substituted α-bromoacetophenone in ethanol. 1-(1,3,4,6-Tetra-O-benzyl-2-deoxy-β-D-glucopyranos-2-yl)thiourea was an important intermediate, and its synthetic methods were discussed by comparing two different synthetic routes. Moreover, 2-isothiocyanate-1,3,4,6-tetra-O-benzyl-2-deoxy-β-D-glucopyranose was obtained in a new and convenient way. Finally, a series of novel glycosyl incorporated with thiazole moiety was synthesized in good purities and overall yields.

■ Synthesis and Antimicrobial Evaluation of Some Novel Thiazole, 1,3,4-Thiadiazole and Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine Derivatives Incorporating Pyrazole Moiety

Abdou O. Abdelhamid,* Ahmad S. Shawali, Sobhi M. Gomha, and Waleed A. M. A. El-Enany

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

Abstract

New series of novel functionalized thiazoles, 1,3,4-thiadiazoles and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines containing pyrazole moiety were synthesized using 4-acetylpyrazole as a precursor. The structures of the compounds prepared were confirmed by both spectral and elemental analyses and by alternative synthetic routes. The mechanisms of the studied reactions were also discussed. Sixteen compounds were evaluated for their in vitro antimicrobial activity. The results proclaimed that some of the tested compounds exhibited moderate to significant antibacterial and antifungal activities. Compounds 11e, 11a, and 11d exhibited high antibacterial activity against Bacillus subtilis compared with reference drug (Ampicillin) while compounds 11a, 6g, 18e, 18a, 11d, 6a, 11c, 11b and 6d exhibited higher antifungal activity against Syncephalastrum racemosum than reference drug (Amphotericin B).

■ Synthesis and Antibacterial Activity of Tripropeptin C Derivatives Containing the Pyrimidine Ring System

Sehei Hirosawa, Yoshiaki Takahashi,* Ayumi Murotani, Hideki Hashizume, Toshiaki Miyake, and Yuzuru Akamatsu

*Hiyoshi branch, Institute of Microbial Chemistry (BIKAKEN), 3-34-17, Ida Nakahara-ku, Kawasaki, Kanagawa 211-0035, Japan

Abstract

A series of modifications to the terminal guanidine group of the arginine residue in tripropeptin C was performed, and the corresponding pyrimidine derivatives were synthesized as a part of a structure-activity relationship study. Some of the resulting compounds maintained excellent antibacterial activity. Our findings indicated that the guanidine group in tripropeptin C is not essential for the antibacterial activity of this compound, and the possibility of chemical modification of the guanidine group was demonstrated.

■ Iron(III) Tetranitrophthalocyanine Chloride Immobilized on Activated Carbon: Efficient, Excellent Chemoselectivity and Recyclable Catalyst for Synthesis of 2-Substituted Benzimidazoles

Jun Qiu, Yaodu Zhang, Chengwen Hua, Xiaofeng Gou, Bang Chen, and Junlong Zhao*

*College of Chemistry & Materials Science, Northwest University, Xi’an, Shaanxi 710069, China

Abstract

The efficient and chemoselective preparation of 2-substituted benzimidazoles was established through the coupling of o-phenylenediamine with aldehydes by using iron(III) tetranitrophthalocyanine chloride immobilized on activated carbon as efficient catalyst in ethanol at room temperature. This method tolerated a variety of functional groups and had several advantages such as environmental friendliness, ease of manipulation, and a short reaction time. In addition, this catalyst can be recovered and reused for multiple cycles without loss in its catalytic activity.

■ Facile One-Pot Synthesis of Cyclic N-Sulfonylamidines from Lactam and Sulfonamide

Ayinigeer Mulati and Abudureheman Wusiman*

*School of Chemistry & Chemical Engineering, Xinjiang Normal University, Xinyi Road No 102, Urumqi, Xinjiang 830054, China

Abstract

A simple method has been developed for one-pot synthesis of five-, six- and seven-membered cyclic N-sulfonylamidines from lactams and sulfonamides under mild conditions. The method involves a Vilsmeier like reaction promoted by phosphoryl chloride. Detailed synthetic studies showed that the corresponding substituted N-sulfonylamidines were obtained in moderate to good yields.

■ Synthesis of Isocoumarins: Rhenium Complex-Catalyzed Cyclization of 2-Ethynylbenzoic Acids

Rui Umeda, Shunya Yoshikawa, Kouji Yamashita, and Yutaka Nishiyama*

*Faculty of Chemistry and Materials Engineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan

Abstract

When 2-ethynylbenzoic acids were treated with a catalytic amount of a rhenium complex, such as ReCl(CO)5, 6-endo cyclization of 2-ethynylbenzoic acids proceeded with a high selectivity to give the corresponding isocoumarins in moderate to good yields.

■ A General Synthesis of Novel Quinoline-Based Isoindolin-1-one Derivatives

Hong Zhang and Yang Li*

*Institute of Superfine Chemicals, Bohai University, 19 Keji Road, Jinzhou 121000, China

Abstract

A simple and general one-pot protocol for the synthesis of a series quinoline-based isoindolin-l-ones, namely 7-chloro-2-substituted-2,3-dihydro- 1H-pyrrolo[3,4-b]quinolin-1-ones (5a-p) is described, involving a cascade Williamson-type condensation reaction of ethyl 6-chloro-2-(chloromethyl)- quinoline-3-carboxylate (3) with aromatic amines (4a-i), aliphatic amines (4j-m) and aliphatic diamines (4n-p) and subsequent intramolecular C-N bond cyclization of the resulting intermediates in refluxing EtOH–AcOH (v/v, 10:1) solvent system in a single synthetic operation.

■ Bifurans via Palladium-Catalyzed Suzuki Coupling

Jun Zhang, Peijun Ye, Lu He, Ting Yuan, and Qiancai Liu*

*School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China

Abstract

Sixteen 2,2’-bifurans with aryl substituents are reported. The copper-mediated oxidative coupling of lithium salt of furan led to the formation of 2,2’-bifuran, which was brominated with either 2 eq. or 4 eq. NBS to afford 5,5’-dibromo-2,2’-bifuran and 3,3’,5,5’-tetrabromo-2,2’-bifuran. The palladium- catalyzed Suzuki reactions between dibromo or tetrabormo-bifuran and arylboronic acid were employed to furnish the title compounds, which were characterized by NMR spectra and mass spectra.