HETEROCYCLES

■ Contents

■ Preparation of Some Novel Trisubstituted 1,3,5-Triazines and Hybrid Linker Mode 1,3,5-Triazine Derivatives and Their Biological Evaluation

Nobuko Mibu, Kazumi Yokomizo, Kanae Yamada, Junko Matsuyama, Syoko Tomonaga, Izumi Sakai, Ryo Sato, Yuki Kawano, Yumemi Matsumoto, Yuka Fujita, Yusuke Inoue, Masaya Iida, Kaneto Hashiguchi, Jian-Rong Zhou, Makoto Furutachi, and Kunihiro Sumoto*

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

Abstract

We report a new route to the preparation of C3-symmetrical multivalent hybrid-type molecules having a tris-aminoethylamine (TAEA) linker group and 1,3,5-triazine recognition moieties in the molecule and we also report the results of biological evaluation of their anti-herpes simplex virus type 1 (anti-HSV-1) activity and cytotoxic activity against Vero cells. Among the tested compounds, a new mid-size C2-symmetrical multivalent hybrid-type molecule (10aq) showed a high level of anti-HSV-1 activity (EC50 = 19.7 μM) with low cytotoxicity (CC50 > 200 μM) against Vero cells. A new CS-symmetrical multivalent derivative (4ab) also showed high anti-HSV-1 activity (EC50 = 1.77 μM) with low cytotoxicity (CC50 > 200 μM). The hybrid-type C2-symmetrical multivalent mid-size molecule (10aq) seems to be an interesting new lead in the search for new hybrid-type symmetrical multivalent antiviral compounds.

■ Diastereoselective Synthesis of 3-Alkylindoloquinolizine Derivatives via Regiospecific Oxidative Cyclization

Susana Morales-Barba, Joel L. Terán, Dino Gnecco, María L. Orea, David M. Aparicio, Víctor Gómez-Calvario, and Jorge R. Juárez*

*Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edif. IC8, Ciudad Universitaria 72570, Mexico

Abstract

3-Alkylindoloquinolizine alkaloids were synthetized in two steps from enantiopure 3-alkylpiperidines through sequential N-alkylation and regiospecific and diastereoselective oxidative cyclization.

■ The Use of Formaldehyde in the Rhodium-Catalyzed Linear-Selective Hydroformylation of Vinylheteroarenes

Jian Pan, Tsumoru Morimoto,* Hideyuki Kobayashi, Hiroki Tanimoto, and Kiyomi Kakiuchi

*Division of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan

Abstract

An accessible protocol for the linear-selective hydroformylation of vinylheteroarenes using formaldehyde as a substitute for syngas is reported. The simultaneous use of BIPHEP and Nixantphos ligands permitted a high regioselectivity (linear/branched = up to 93/7) and moderate yield of isolated product (up to 84%) to be obtained. Under such catalytic conditions, vinylheteroarenes containing a vinyl group at the 2-position in the heterocycle ring reacted more linear-selectively with formaldehyde than at the 3-position.

■ An Efficient Synthesis of N-Aryl-2-(indol-3-yl)acetamides via Multi-Component Reactions

Guo-Ning Zhang, Mengye Zhang, Xiaonan Du, Mei Zhu, Juxian Wang,* Daqing Shi,* and Yucheng Wang*

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

Abstract

An efficient synthesis of N-aryl-2-(indol-3-yl)acetamide derivatives via a four-component reaction of arylglyoxal monohydrate, Meldrium’s acid and anilines under microwave irradiations is described. This protocol has the advantages of high efficiency, mild reaction conditions, a one-pot procedure, and materials available.

■ Synthesis of N-alkyl Substituted Azasugar-tetrazole Hybrid Molecules via Ugi-azide Reaction

Hairong Luo,* Bangjian Xu, Lingyu Zhang, and Meihang Chen

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

Abstract

An effective and facile method for the synthesis of N-alkyl substituted azasugar-tetrazole hybrid molecules is described. The one-pot Ugi-azide reaction provides convenient access to synthesis of α-tetrazolyl azasugar scaffolds as potential glucosidase inhibitors in moderate to good yields in methanol catalyst by lewis acid under mild conditions.

■ Conformational Control of a Pyrrole-Based Amide Pentamer by Dihydrogen Phosphate Anion Binding

Jiulong Li, Guoping Li,* Chaocao Lu, Bu Htan, Chunmiao Ma, and Quan Gan*

*School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China

Abstract

Conformational control is of importance for compounds to implement their properties and functions. In this work, a pyrrole-based amide pentamer 1 was synthesized. NOESY NMR experiments show it adopts two main conformations, one of which can be sorted out and stabilized via binding of a dihydrogen phosphate anion.

■ Agesamines A and B, New Dibromopyrrole Alkaloids from the Sponge Agelas sp.

Ayako Katsuki, Hikaru Kato, Yuji Ise, Fitje Losung, Remy E. P. Mangindaan, and Sachiko Tsukamoto*

*Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan

Abstract

New dibromopyrrole alkaloids, agesamines A (1) and B (2), were obtained as an inseparable epimeric mixture from a marine sponge Agelas sp., collected in Indonesia. The planar structures were elucidated by analysis of spectroscopic data, and the absolute configuration was determined by the calculated ECD spectrum.

■ Synthesis of [1,4]Oxathiino[2,3-d]pyrimidines Starting with 4,6-Dichloro-2-(methylsulfanyl)pyrimidine

Kazuhiro Kobayashi,* Kota Yamasaki, Hidetaka Hiyoshi, and Kazuto Umezu

*Applied Chemistry Field, Chemistry and Biotechnology Course, Department of Engineering, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

A convenient method for the preparation of 7-(het)aryl[1,4]oxathiino[2,3-d]pyrimidine derivatives using an easily operated two-step sequence starting from 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP) have been developed. Thus, the starting material is treated with LDA to generate the 5-lithio derivative, which is allowed to react with sulfur and then phenacyl bromide and its derivatives to give 1-(het)aryl-2-{[4,6-dichloro-2-(methylsulfanyl)pyrimidin-5-yl]sulfanyl}ethanones. These pyrimidinyl ketones undergo ring closure upon treatment with triethylamine to provide the corresponding desired products in reasonable overall yields from DCSMP.

■ Visible-Light-Enabled C(sp2)–H Difluoroalkylation of Aldehyde-Derived Hydrazones Under Metal-Free Conditions

Wen-Qiang Liu, Wei-Hao Chen, Xiao-Xuan Li, Wei-Ke Tang, Ting-Ting Tao, and Yi-Si Feng*

*School of Chemistry and Chemical Engineering, Hefei University of Technology, Anhui 230009, China

Abstract

A Eosin Y-catalyzed C(sp2)-H difluoromethylation of aldehyde-derived hydrazones between difluoroalkyl bromides and aldehyde-derived hydrazones is reported. This reaction has a wide range of substrates and occurs under metal-free condition. A mechanism that involves a difluoroacetate radical via single electron transfer (SET) pathway is proposed for this reaction.

■ Correction to “Facile and Efficient Access to Tetrahydrobenzo[b]pyrans Catalyzed by N,N-Dimethylbenzylamine”: HETEROCYCLES, 2016, 92, 75, DOI: 10.3987/COM-15-13360

Hamzeh Kiyani* and Mozhgan Sadat Jalali

*School of Chemistry, Damghan University, 36719-41167 Damghan, Iran

■ Correction to “One-Pot and Efficient Synthesis of 5-Aminopyrazole-4-carbonitriles Catalyzed by Potassium Phthalimide”: HETEROCYCLES, 2017, 94, 276, DOI: 10.3987/COM-16-13623

Hamzeh Kiyani* and Maryam Bamdad

*School of Chemistry, Damghan University, 36719-41167 Damghan, Iran

■ Correction to “Synthesis of Erlenmeyer-Plöchl Azlactones Promoted by 5-Sulfosalicylic Acid”: HETEROCYCLES, 2017, 94, 1314, DOI: 10.3987/COM-17-13711

Hamzeh Kiyani* and Shiva Aslanpour

*School of Chemistry, Damghan University, 36719-41167 Damghan, Iran

■ Correction to “Sulfanilic Acid-Catalyzed Green Synthesis of 4-Arylidene-2-phenyl-5(4H)-oxazolones”: HETEROCYCLES, 2018, 96, 297, DOI: 10.3987/COM-17-13847

Hamzeh Kiyani* and Shiva Aslanpour

*School of Chemistry, Damghan University, 36719-41167 Damghan, Iran