HETEROCYCLES

■ Contents

■ Heterocycles Award

HETEROCYCLES Announcement*

*The Japan Institute of Heterocyclic Chemistry, 1-7-17, Motoakasaka, Minato-ku, Tokyo 107-0051, Japan

■ Total Syntheses of Liphagal: A Potent and Selective Phosphoinositide 3-Kinase α (PI3Kα) Inhibitor from the Marine Sponge Aka coralliphaga

Koichi Narita and Tadashi Katoh*

*Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

Liphagal, isolated from the marine sponge Aka coralliphaga, exhibits a potent and selective inhibitory activity against phosphoinositide 3-kinase α (PI3Kα). This marine natural product has attracted significant attention because of its potential as a promising candidate or new lead for the development of novel molecular targeted anticancer agents. In this review, the reported total syntheses of liphagal are presented with a particular focus on the methodologies and strategies employed.

■ Efficient One Pot Synthesis of Chromenonaphthyridine Derivatives by CuI/InCl3 Catalyzed Aza Diels-Alder Reaction

Pradip Kumar Maji* and Ayan Mahalanobish

*Department of Chemistry, Bidhan Chandra College , Asansol, West Bengal, India

Abstract

A mild and efficient method for the synthesis of chromenonaphthyridine derivatives via domino reaction of aminopyridine and different O-propargylated salicylaldehydes using CuI/InCl3 as an efficient catalyst, refluxed in acetonitrile is reported. Mild reaction condition, operational simplicity, good to excellent yield and easy isolation of product is the silent feature of this reaction.

■ A Facile Synthesis of Novel Heterocyclic Compounds with Anticipated Antibacterial Activities Based on Coumarin Moiety

Asmaa Kamal Mourad,* Fathia Korany Mohamed, and Ahmed Yousef Soliman

*Department of Chemistry, Faculty of Science, Fayoum University, 63514 Fayoum, Egypt

Abstract

A novel series of coumarin derivatives has been disclosed by allowing 2-aminonicotinonitrile derivative 1 to undergo alkylation, diazotization, and condensation reactions. Moreover, different reagents, such as thiourea, phenyl isothiocyanate, carbon disulfide, ethylenediamine, and hydroxylamine hydrochloride, have been exploited to synthesize more coumarin derivatives, aiming to increase the synthetic potential of coumarin and study the antibacterial activities of the newly synthesized compounds.

■ A Convenient Synthesis of Indole and 1,4-Dihydropyridine Hybrid Macromolecules by Dimerization of [2-(1H-Indol-3-yl)ethyl]pyridinium Salts

Gang Ling, Jing Zhang, Rong-Zheng Zhang, and Fu-She Han*

*Key Lab of Synthetic Rubber, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China

Abstract

The design and synthesis of a novel type of macrocyclic compounds containing indole and 1,4-dihydropyridine heterocyclic subunits is presented. The key reaction involved in the synthesis was a base-mediated dimerization of [2-(1H-indol-3-yl)ethyl]pyridinium salts. The structure of the macrocycles was unambiguously confirmed by NMR and HRMS spectroscopic and X-ray single crystal diffraction.

■ Synthesis, Antifungal Activity and QSAR of Novel Pyrazole Amides as Succinate Dehydrogenase Inhibitors

Shijie Du, Zhonghao Li, Zaimin Tian, and Lu Xu*

*College of Material and Chemical Engineering, Tongren University, Tongren, 554300, China

Abstract

We design and synthesize a series of novel pyrazole amides based on the commercialized fungicides and our previous work. The antifungal activity was tested in vitro by mycelial growth inhibition assay. The results show that all the compounds are of antifungal activities against the tested fungi at different levels. Among them, N-(2-(7-bromo-5-chloro-1H-indazol-1-yl)phenyl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide (Vk) exhibited higher antifungal activity than boscalid against two fungi. Molecular docking study revealed that the carbonyl oxygen atom of Vk forms two hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173.

■ Synthesis, Transformation of 3-[(4-Arylthiazol-2-yl)(p-tolyl)amino]propanoic Acids, Bis(thiazol-5-yl)phenyl-, Bis(thiazol-5-yl)methane Derivatives, and Their Antimicrobial Activity

Birutė Grybaitė, Rita Vaickelionienė, Maryna Stasevych, Olena Komarovska-Porokhnyavets, Volodymyr Novikov, and Vytautas Mickevičius*

*Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, 50254 Kaunas, Lithuania

Abstract

Bis(thiazol-5-yl)phenyl- and bis(thiazol-5-yl)methanes were synthesized by the reaction of 2,4-disubstituted thiazoles with aromatic aldehydes or formaldehyde. In addition, modification of the carboxyl group of the molecule was carried out. The reactions afforded compounds bearing various heterocyclic fragments. All the synthesized compounds were tested for their effect on Escherichia coli, Staphylococcus aureus and Mycobacterium luteum bacteria and Aspergillus niger and Candida tenuis fungi strains. Some of them exhibited antibacterial activity against test-culture Mycobacterium luteum.

■ Synthesis of Triazol Cn-Ribonucleoside Phosphoramidites Using β-Ribofuranosyl-Cn-acetylenes for RNA Catalysis Probing

Hiroki Yoneyama, Fumiko Hikasa, Daiki Fujisue, Yoshihide Usami, Zheng-yun Zhao, and Shinya Harusawa*

*Department of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

Novel C4-linked triazol C0-, C1- and C2-ribonucleoside phosphoramidites for RNA catalysis probing were synthesized from β-ribofuranosyl-Cn-acetylenes (n = 0–2), which were efficiently prepared by fragmentation of tetrazoles derived from cyanophosphates. N-Pivaloyloxymethyl moiety was selected for the protection of triazole-N, whose properties under acidic and basic conditions were investigated.

■ Synthesis of Dibromo Compounds Containing 2,6-Dioxabicyclo[3.1.1]heptane Similar to Core Moiety of Thromboxane A2

Yoshihiko Nokura, Atsuo Nakazaki, and Toshio Nishikawa*

*Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan

Abstract

Thromboxane A2, a potent platelet aggregation factor, contains a labile 2,6-dioxabicyclo[3.1.1]heptane as the core moiety. Dibromo compounds with a similar core structure were synthesized by the cyclization of tribromides derived from D-glucal.

■ Flavones from the Fruits of Vernicia fordii and Their Anti-Tobacco Mosaic Virus Activity

Min Zhou, Rui-Qi Zhang, Yan-Jun Chen, Ling-Min Liao, Yan-Qi Sun, Zu-Hong Ma, Qiao-Fen Yang, Ping Li, Wei-Guang Wang,* and Qiu-Fen Hu*

*School of Ethnic Medicine, Yunnan Minzu University, Kunming 650031, China

Abstract

Three new flavones (1–3), together with six known flavones (4–9), were isolated from the fruits of Vernicia fordii collected from Hunan province of China. Their structures were characterized by means of extensive spectroscopic analyses. Compounds 1–3 and 9 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that compound 9 exhibited high anti-TMV activity with inhibition rate of 32.6%. This inhibition rate is close to that of positive control (33.8%). Compounds 1–3 also showed potential anti-TMV activities with inhibition rates of 26.8%, 29.2%, and 25.7%, respectively.

■ Novel Trivalent C3-Symmetrical Phenylboronic Acid Pinacol Esters and Their Biological Evaluation

Makoto Furutachi, Saho Fuchigami, Kenta Ako, Saho Goto, Toshiaki Gondo, Mai Takuse, Moeko Yoshida, Kazumi Yokomizo, Jian-Rong Zhou, Aya Matsunaga, Nozomi Hiraga, Nobuhiro Kashige, Fumio Miake, and Kunihiro Sumoto*

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

Abstract

We report the preparation of newly designed trivalent C3-symmetrical cyclic phenylboronic acid derivatives constructed on a symmetrical benzene or a cyclohexane ring. The synthesis of these C3-symmetrical molecules 4 was accomplished by an amide bond formation reaction using amino-substituted phenylboronic acid pinacol esters 2 and C3-symmetrical benzene-1,3,5-tricarboxylic acid trichloride 3a or cyclohexane-1,3,5-tricarboxylic acid trichloride 3b in the presence of Et3N. We confirmed that this procedure is conventionally applicable to the preparation of targeted C3-symmetrical cyclic boronic acid derivatives 4 in good to excellent yields. We also report the results of biological evaluation of the prepared compounds.

■ Diastereospecific Intramolecular Cyclopropanation of Enantiopure 8-Bromo-3-phenylhexahydrooxazolo[3,2-a]pyridin-5-ones

Anna Vargas, María L. Orea,* Dino Gnecco,* David M. Aparicio, 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, Pue., Mexico

Abstract

A diastereospecific intramolecular cyclopropanation of (3R,8R,8aS)-8-bromo-3-phenylhexahydrooxazolo[3,2-a]pyridin-5-one 1 and (3R,8S,8aS)-8-bromo-3-phenylhexahydrooxazolo[3,2-a]pyridin-5-one 2 to generate the corresponding enantiopure 3-phenylhexahydro-5H-cyclopropa[3,4]pyrrolo[2,1-b]oxazol-5-ones 3 and 4 in high yield is described.