HETEROCYCLES

■ Contents

■ Synthesis and Optical Properties of Substituted 5,6,7,8-Tetraaza-azuleno[1,8-b,c]fluorenes, Small Organic Molecules of Unusual Topology Designed for Circularly Polarized Luminescence

Tadeusz Lemek,* Krzysztof Danel, Oskar Michalski, and Wojciech Nitek

*Tadeusz Lemek; R&D Institute of Celon Pharma S.A., ul. Marymoncka 15, 05-152 Kazuń Nowy, Poland

Abstract

Helical photoluminescent substituted 5,6,7,8-tetraaza-azuleno[1,8-b,c]fluorenes were obtained as racemates. The compounds have been designed for circularly polarized luminescence. Some of the compounds were separated on to enantiomers with chiral HPLC column and showed Cottons effects in absorption and emission spectra. The experimental results were compared with DFT calculations, which led us to assess the chirality to structure.

■ Efficient Synthesis of Novel Spiro[indoline-3,5'-pyrano[2,3-d]pyrimidin]-2-one Derivatives and Antitumor Activity Evaluation

Zhenhua Li,* Guoqing Huang, Dayou Rong, Yingyan Cao, and Ronghui Hu

*College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, P.R. China

Abstract

An efficient method for synthesis of the spiro-[indoline-3,5'-pyrano[2,3-d]pyrimidin]-2-one derivatives from 2'-amino-2-oxo-spiro[indoline-3,4'-pyran]-3'-carbonitriles using bis(trichloromethyl) carbonate (BTC) and triphenylphosphine oxide (TPPO) was developed. A series of target compounds with broad substrate scope were synthesized in moderate to good yields. In addition, the antitumor activities against four cancer cell lines A549, HepG-2, MCF-7, and HeLa were evaluated using 5-FU and cisplatin as reference, all compounds showed good antitumor activity compared with the standard drugs.

■ Synthesis of 2-Trifluoroacetonyl-3-alkyl/alkoxychromones and Their Reactions with 1,2-Bidentate Nucleophiles

Iryna M. Biletska, Galyna P. Mrug, Yaroslav O. Prostota, Kostyantyn M. Kondratyuk, Svitlana P. Bondarenko, and Mykhaylo S. Frasinyuk*

*V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of National Academy of Science of Ukraine, Kyiv 02094, Ukraine

Abstract

The reaction of 3-substituted 2-methyl/2-benzyl/2-(2-phenethyl)chromones with trifluoroacetic anhydride in presence of potassium trifluoroacetate was investigated. It was established that the nature of substituent in position 3 of chromone ring has no crucial influence/limitation on this reaction, whereas only in the case of 2-benzyl substituent (in addition to 2-sec-alkyl group) no reaction was occurred at all. Reaction of synthesized 2-(3,3,3-trifluoro-2-oxopropyl)chromones with hydrazine dihydrochloride afforded 3-(2-hydroxyphenacyl)-5-trifluoromethylpyrazoles, but reaction with hydroxylamine led to oximation of side-chain carbonyl group. Reaction of 2-trifluoromethylchromones with 1,2-bidentate nucleophiles led to substituted 2-hydroxyphenylpyrazoles and isoxazoles. Mechanisms of these ring-transformation reactions are discussed.

■ Facile Synthesis of Fully Conjugated Aminopyrazine Based Diazobenzenes and Diazoaminobenzenes with Aryldiazonium Salts

Idris Karakaya*

*Department of Chemistry, College of Basic Sciences, Gebze Technical University, 41400 Gebze, Turkey

Abstract

Herein, we report the diazotization of aminopyrazine achieved in good to excellent yields using electronically disparate aryldiazonium salts at room temperature. These novel and fully conjugated diazobenzenes and diazoaminobenzenes were characterized utilizing NMR, HRMS, single crystal X-ray diffraction, and UV–Vis techniques. Depending on the position of the functional groups substituted on the aryldiazonium salts and their ability to forge hydrogen bonds, these reactions can diverge into two possible pathways to give diazobenzenes or diazoaminobenzenes selectively. Based on the results of UV-Vis spectroscopic analysis, it was determined that the maximum absorbance band of the compounds was between 333 nm and 363 nm due to their interacting π-π* transitions. These results are further supported by DFT calculations, showing these molecules exhibit high absorbance.

■ Ultrasound Assisted One Pot, Three-Component Reaction for Facile Design of Novel 1,2,3-Diazaphosphole, 1,5,2-Diazaphosphinine and 1,5,2-Diazaphosphepine Compounds Containing Coumarin Ring

Tarik E. Ali,* Mohammed A. Assiri, Abdullah Y. Alzahrani, and Mohamed A. Salem

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo, Egypt

Abstract

We have designed novel 1,2,3-diazaphosphole, 1,5,2-diazaphosphinine and 1,5,2-diazaphosphepine compounds containing a coumarin ring. The method depended on one-pot, three-component reaction of 3-(2-bromoacetyl)-2H-chromen-2-one (1) and diethyl phosphite in the presence of diamine reagent under ultrasonication effect at 50 oC. The possible reaction mechanisms of the formation of these products were displayed and discussed. The structures of isolated products were established by elemental analyses and spectral tools.

■ Synthesis and Enzyme Inhibitory Properties of Quinoxaline Bridged Bis(imidazolium) Salts

Murat Yiğit,* Yeliz Demir, Ali Arınç, Beyhan Yiğit, Murat Koca, İsmail Özdemir, and İlhami Gülçin

*Department of Chemistry and Chemical Process Technologies, Vocational School of Technical Sciences, Adiyaman University, 02040-Adıyaman, Turkey

Abstract

In this study, a series of new salts containing quinoxaline and imidazole moieties were synthesized in good yield by the reaction of 2,3-bis(bromomethyl)quinoxalines and 1-alkylimidazoles in N,N-dimethylformamide. These salts were characterized by elemental analysis, IR, 1H NMR and 13C NMR spectroscopy, which support the proposed structures. Furthermore, the enzyme inhibition activities of these compounds were investigated. They showed highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (Ki values are in the range of 44.80±14.87 to 288.64±42.68 nM, 21.50±4.76 to 187.30±22.43 nM, and 5.81±0.71 to 164.52±26.0 nM for AChE, hCA I, and hCA II, respectively). Compound 3 showed the best inhibition effect for hCA I and compound 4 showed the best inhibition effect for hCA II and AChE.

■ New Dimeric Cytisine-Type Alkaloid and Lavandulyl Biflavonoid from Sophora flavescens Ait. and Their Inhibitory Effect on Cancer Cells

Shengxue Chen, Yan Liu, Chenting Meng, Min Li, Chunping Yuan, and Xiaoying Yin*

*School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, China

Abstract

Two new dimeric compounds with antitumor activity were extracted for the first time from Sophora flavescens Ait. using several chromatographic separation methods. Compound 1 (sophobikushenine) is a dimeric cytisine-type alkaloid connected by an eight-membered heterocycle ring, and compound 2 (sophobiflavanone) is a lavandulyl biflavonoid consisting of a skeleton including nitrogen atoms as heteroatoms. The structures of the two compounds were elucidated using one- and two-dimensional NMR, ECD, and HR-ESI-MS. The inhibitory effects of the new compounds against A431 and BT474 were evaluated in vitro implementing CCK-8 and scratch assays. Sophobiflavanone inhibited the growth of A431 cells with an IC50 value of 37.77 ± 0.98 μM and BT474 cells with an IC50 value of 38.13 ± 0.31 μM; further, it exhibited a strong antimigratory activity toward 4T1.

■ Synthesis and Antimicrobial Activity of 2,5-Bis(pyrazol-3-yl or triazol-4-yl)-1,3,4-oxadiazoles

Hanan A. Mohamed, Bakr F. Abdel-Wahab, Eman Sabry, Benson M. Kariuki, and Gamal A. El-Hiti*

*Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia

Abstract

The reaction of pyrazole-3-carbohydrazide (1) or 1,2,3-triazole-4-carbohydrazides 5a,b and 2-(ethoxymethylene)malononitrile (2) in ethanol under reflux conditions afforded the corresponding N,N'-diacylhydrazines 3 or 6a,b, respectively in high yields. Ring closure of 3 or 6a,b in the presence of phosphorus oxychloride furnished the corresponding 2,5-bis(heterocyclic)-1,3,4-oxadiazoles 4 or 7a,b, respectively in good yields. The synthesized heterocyclic compounds showed moderate activity against Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli.

■ Synthesis, Characterization and Biological Screening of New N-Substituted-7-chloro-4-hydroxy-2-quinolone-3-carboxamides as Promising Anticancer Agents

Aya Mohammed kheir Al-Zuheiri, Kamal Sweidan,* Mohammed Kamal Harb, Sanaa K. Bardaweel, Mahmoud Sunjuk, and Dima A. Sabbah

*Department of Chemistry, The University of Jordan, Amman 11942, Jordan

Abstract

A new set of 7-chloro-4-hydroxy-2-quinolone-3-carboxamide derivatives has been synthesized in good yields by using simple procedure. The prepared compound has been characterized using different spectroscopic techniques including high resolution mass spectrometry (HRMS), infrared spectroscopy (IR), one-dimensional (1D), two-dimensional (2D) nuclear magnetic resonance (NMR), and by elemental analysis (EA). The target products have been tested as anticancer agents against cell lines; human colon carcinoma (HCT-116), breast adenocarcinoma (MDA-231), epithelial colorectal adenocarcinoma (Caco-II), and normal cell lines. Results indicated that compound demonstrated selective inhibitory activity; compound 14 exerted high activity against HCT-116 cell line (IC50 = 87.45 µM), compound 5 exhibited high activity against (MDA-231) cell line (IC50 = 23.66 µM), and compound 10 demonstrated high activity against (Caco-II) cell line (IC50 = 35 µM).

■ Antimicrobial Acetophenone and Phenalenone Derivatives from a Soil-Derived Fungus Penicillium verrucisporum JX1

Huiping Hu, Yuting Tang, Hengyi Lin, Zheng Ma, Penglai Fan, Xiachang Wang, Yongyong Zhang,* and Jiarong Pan*

*Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou 310018, China

Abstract

A new acetophenone derivative, named veracetophenone (1), along with six known compounds communol F (2), clavatol (3), (+)-scleroquinone (4), (‒)-trypethelone (5), (‒)-sclerodin (6), and (‒)-scleroderolide (7), were isolated from a soil-derived fungus Penicillium verrucisporum JX1. Their structures were identified on the basis of spectral analysis of 1D, 2D-NMR, and HRESIMS. The configuration of 4 was depicted based on spectroscopic data as well as optical property. Their antibacterial and antifungal activities were also evaluated.

■ Semisynthesis of Conjugates from Matrine/Cholesterol with Piperic Acid/Piperic Acids-Like as Insecticidal and Aphicidal Agents

Linlin Jiang, Hailong Wang, Meng Hao, Zhen Wang, and Min Lv*

*College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi Province, P.R. China

Abstract

To find natural-product-based pesticide candidates, a series of conjugates of cholesterol/matrine and piperic acid/piperic acids-like were semi-prepared as insecticidal and aphicidal agents against Mythimna separata Walker and Aphis citricola van der Goot. Notably, two steric structures were confirmed by single-crystal diffraction. Importantly, compounds IIc, IVc and Vb exhibited (3.2 and 3.5 folds promising insecticidal activity of cholesterol) more potent insecticidal activity than toosendanin. Compounds Ia (1.45-fold of matrine) and IVb (2.2-fold of cholesterol) showed potent aphicidal activity.