HETEROCYCLES

■ Contents

■ Synthetic Studies on Natural Pterin Glycosides

Tadashi Hanaya* and Hiroshi Yamamoto

*Department of Chemistry, Faculty of Science, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

Some pterins having various kind of sugars attached to the hydroxyalkyl side-chain at C-6 are known to occur in certain prokaryotes as exemplified by 2'-O-(α-D-glucopyranosyl)biopterin isolated from various kinds of cyanobacteria. A synthetic exploration of various types of glycosides of biopterin and related pterins has been undertaken owing to a marked interest in their physiological functions and biological activities as well as the structural proof of those natural products. This review summarizes our synthetic studies on natural pterin glycosides by employing the appropriately protected N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitrophenyl)ethyl]pterin derivatives as glycosyl accepters.

■ Biological Evaluation of Pyrimidopyrimidines as Multi-Targeted Small Molecule Inhibitors and Resistance Modifying Agents

Reda Abdel-Rahman and Kamelia El-mahdy*

*Department of Chemistry, Faculty of Education, Ain Shams University, El-Maqreezy St, Roxy, Heliopolis, Cairo 11711, Egypt

Abstract

This review provides detailed methods for the synthesis of pyrimidopyrimidine derivatives and their biological properties as uptake inhibitors. The main accent was put on the important findings in pyrimidopyrimidine chemistry and is useful for developing tumor growth inhibitors based on pyrimidopyrimidine.

■ RUTHENIUM PORPHYRIN CATALYZED FRIEDEL–CRAFTS TYPE REACTION OF ARENES WITH IMINES

Takuma Terada, Takuya Kurahashi,* and Seijiro Matsubara*

*Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoudai-katsura, Nishikyo, Kyoto 615-8510, Japan

Abstract

Cationic ruthenium porphyrin complex was found to be an efficient catalyst for the Friedel–Crafts type reaction of arenes with imines. The use of a structurally rigid tetradentate porphyrin as the equatorial ligand and weakly coordinating axial ligand is the key to bring out the catalytic reactivity of ruthenium for the reaction.

■ Novel Heterocyclic Derivatives of 2-Quinolinone Associated with Antibacterial and Antitumor Potencies

Hany M. Hassanin* and Somaya M. El-Edfawy

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo 11711, Egypt

Abstract

3-(2,2-Dichloroacetyl)-4-hydroxy-1-methyl-quinolin-2(1H)-one (2) was utilized to obtain several new quinolinones bearing imidazole, quinoxaline, 1,2,4-triazine, pyridotriazine and triazolotriazine heterocycles as substituents at position 3. Condensation of compound 2 with aminotriazine 12 afforded the iminone 14 which was subjected to annellation reactions leading to some new quinolinones fused at face [c]; viz. pyrazole, pyrimidine and benzodiazepine. Structure of the new compounds was confirmed by spectral and elemental analyses. The synthesized compounds were screened in vitro for their antimicrobial and antitumor activities.

■ Suzuki-Miyaura Coupling Reactions of 3,5-Dichloro-1,2,4-thiadiazole

Abdelbasset A. Farahat and David W. Boykin*

*Department of Chemistry, Georgia State University, P.O. Box 4098, Atlanta, Georgia 30302-4098, U.S.A.

Abstract

3,5-Dichloro-1, 2, 4-thiadiazole was allowed to react with different aryl boronic acids under different Suzuki-Miyaura coupling conditions: at room temperature 5-aryl-3-chloro-1, 2, 4-thiadiazoles were obtained and at toluene reflux temperature the products were 3,5-diaryl-1, 2, 4-thiadiazoles. Sequential coupling reactions lead to 3,5-diaryl-1, 2, 4-thiadiazoles with non-identical aryl groups. The structure of 3-methoxy-5-(4-methoxyphenyl) -1, 2, 4-thiadiazole was established from X-ray crystallographic data.

■ Synthesis, Reactions, and Rearrangements of 2,4-Diazabicyclo[3.1.0]hexan-3-ones

Helmut Quast,* Josef Walter Stawitz, and Bodo Mueller

*Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany

Abstract

Copper-mediated cyclopropanation of 1,3-dialkyl-1,3-dihydroimidazol-2-ones with diazomethane and methyl diazoacetate yields 2,4-diazabicyclo[3.1.0]hexan-3-ones and the first diaza[4.3.1]propellane. The bicyclic system survives elevated temperatures and in strongly basic and acidic solutions, but drastic conditions cleave the (C-1)–(C-6) bond affording 1,3-dihydroimidazol-2-ones. Catalytic hydrogenation removes N-benzyl groups and opens the (C-1)–(C-6) bond. Lithium aluminium hydride reduces 2,4-dibenzyl-2,4-diazabicyclo[3.1.0]hexan-3-one to a bicyclic aminal. Acid-induced cleavage of its imidazolidine ring is followed by unexpected transformations that probably procede via an acyclic intermediate, which comprises an azomethine ylide and an iminium moiety. 1,3-Cyclization involving both functional groups leads to N,N’-dibenzyl-trans-1,2-cyclopropanediamine, while 1,5-cyclization gives rise to the formation of N-benzylpyrrol along with N-benzylamine.

■ Cytotoxic Alcyonolide Congeners from an Okinawan Soft Coral Cespitularia sp.

Prodip Kumar Roy, Wilmar Maarisit, Sona Rani Roy, Junsei Taira, and Katsuhiro Ueda*

*Department of Chemistry, Biology and Marine Sciences, Faculty of Science, University of Ryukyus, Nishihara-cho, Okinawa 903-0213, Japan

Abstract

Four new alcyonolide congeners (1-4) were isolated from a soft coral Cespitularia sp. together with the known alcyonolide (5). Their structures were determined by spectroscopic and chemical analyses. Compounds 1-5 showed moderate to weak cytotoxicities against HCT 116 cells.

■ Synthesis of 2- and 6-(Dialkylaminoalkylthio)- and 2,6-Bis(dialkylaminoalkylthio)-7-methylpurines

Alicja Kowalska* and Krystian Pluta

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

Abstract

An efficient synthesis of 21 new thiopurines being 2-substituted 6-dialkylaminoalkylthio-7-methylpurines, 6-substituted 2-dialkylaminoalkylthio-7-methylpurines, and 2,6-di(dialkylaminalkylthio)-7-methylpurines was reported. 2-Substituted 6-dialkylaminoalkylthio and 2,6-di(dialkylaminoalkylthio) derivatives were obtained via direct S-dialkylaminoalkylation of the appropriate purinethiones. The different reactivities of the dialkylaminalkylthio groups in positions 2 and 6 towards sodium alkoxides were the key processes in a few step synthesis of 2-dialkylaminoalkylthio derivatives from 2,6-di(dialkylaminalkylthio) derivatives.

■ Two New Chromanone Derivatives from the Roots and Stems of Nicotiana tabacum and Their Cytotoxicity

Dingrong Mou, Wei Zhao, Tao Zhang, Lan Wan, Guangyu Yang, Yongkuan Chen, Qiufen Hu,* and Mingming Miao*

*Key Laboratory of Ethnic Medicine Resource Chemistry, State Ethnic Affairs Commission & Ministry of Education, School of Chemistry and Biotechnology, Yunnan University of Nationalities, Kunming, Jingming South Road, Chenggong New District, Kunming, Yunnan 650500, China

Abstract

Two new chromanone derivatives, tabchromones A and B (1-2), together with four known compunds (3-6) were isolated from the roots and stems of Nicotiana tabacum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D- NMR techniques. Compounds 1-6 were tested for their in vitro cytotoxicity against five human tumor (NB4, A549, SHSY5Y, PC3, and MCF7) cell lines. Compound 1 showed significant inhibitory effect against SHSY5Y cell line, with IC50 values of 2.8 μM, and compounds 2-4 showed moderate activity for some selected cell lines, with IC50 values in the range of 4.8-8.0 μM.

■ SYNTHESIS OF DIhydrodiBENZo[b,f]furo[2,3-d]OXEPINs AND RELATED REACTIONS

Yasunobu Maemura, Yuka Tanoue, and Hiroshi Nishino*

*Department of Chemistry, Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1, Chûou-Ku, Kumamoto 860-8555, Japan

Abstract

Nine dihydrodibenzo[b,f]furo[2,3-d]oxepin derivatives were synthesized by the Mn(III)-based oxidative addition of dibenz[b,f]oxepins at C10-C11 with acetic anhydride, acetylacetone, dialkyl malonates, and malonamide. Oxidative ring-expansion of methyl hydrogen thioxanthenylmalonate with manganese(III) acetate did not give the desired dibenzo[b,f]thiepincarboxylate but produced 2-acetoxy-2-(thioxanthen-9-yl)acetate and thioxanthone.

■ Competitive Condensation and Tandem Cyclization Reactions of 2-Cyano-3-ferrocenylacrylonitrile with Amidines in an Aqueous Medium

Elena I. Klimova,* Marcos Flores-Alamo, José M. Méndez Stivalet, and Tatiana Klimova

*Faculty of Chemistry, National Autonomous University of Mexico, Cd. Universitaria, Coyoacan, C.P. 04510, Mexico

Abstract

The synthesis of a series of ferrocenyl-substituted 2-aminopyridine- and 6-amino-4,5-dihydropyridine-3,5-dicarbonitriles, 4-aminopyrimidine- and 3,4-dihydropyrimidine-5-carbonitriles by reactions of 2-cyano-3-ferrocenylacrylonitrile with amidines in aqueous medium is described. New fused 6-amino-2-ethoxy-4-ferrocenyl-5-ferrocenylmethyl-4,5-dihydropyridine-3,5-dicarbonitrile was prepared in a tricomponent cyclodimerization from 2-cyano-3-ferrocenylacrylonitrile in presence of ethanol. The structures of the obtained compounds were established by IR, 1H and 13C NMR spectroscopy, mass-spectrometry and X-ray diffraction analysis.

■ Synthesis of Novel Trichloromethyl Substituted Azolo[1,3,5]triazines

Dmitrii V. Kalinin, Svetlana A. Kalinina, and Anton V. Dolzhenko*

*School of Pharmacy, Curtin University of Technology, GPO Box U1987, Perth, Western Australia 6845, Australia

Abstract

The triazine ring bearing a trichloromethyl group was annelated to various aminoazoles using a new effective synthetic procedure. The method of preparation involved initial formation of trichloroacetamidines in the reaction of aminoazoles with trichloroacetonitrile followed by the triazine ring closure with triethyl orthoformate affording therefore the titled compounds.

■ Synthesis of 3-Substituted 4-Alkoxyisoquinolin-1-amines by the Reaction of 2-[Alkoxy(lithio)methyl]benzonitriles with Nitriles

Kazuhiro Kobayashi,* Kota Matsumoto, and Kosuke Ezaki

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

Abstract

It has been found that the reaction of 2-[alkoxy(lithio)methyl]benzonitriles, generated in situ from 2-(alkoxymethyl)benzonitriles and two equivalents of lithium diisopropylamide in diglyme at –78 ˚C, with aliphatic and aromatic nitriles provides an efficient method for the one-pot preparation of 3-substituted 4-alkoxyisoquinolin-1-amines.

■ ONE-POT SYNTHESIS OF MACROCYCLIC TETRAlACTONES VIA THE SEQUENTIAL INTER- AND INTRAMOLECULAR [2+2] PHOTOCYCLOADDITION REACTIONS OF Di-2-PYRONES WITH POLYETHYLENE GLYCOL DIMETHACRYLATES

Tetsuro Shimo,* Hideki Matsukubo, and Hui Min Zhang

*Department of Chemistry, Faculty of Engineering, Kagoshima University, Korimoto, Kagoshima 890-0065, Japan

Abstract

The sensitized photocycloaddition reactions of 6,6’-dimethyl-4,4’-[1,7-(1,4,7-trioxaheptyl)]-di-2-pyrone (1a) and 6,6’-dimethyl-4,4’-[1,10-(1,4, 7,10-tetraoxadecyl)]-di-2-pyrone (1b) with polyethylene glycol dimethacrylates (2a-d) afforded macrocyclic tetralactones containing two cyclobutane rings. The reactions of 1a with 2a-d afforded diastereomixtures of macrocyclic crown ether-type structures (3a-d and 3a’-d’) possessing 19– to 28–membered rings across the C5-C6 and C5’-C6’ double bonds of 1a. Similarly, 1b reacted with 2a-d to give the corresponding 22– to 31–membered-ring products (4a-d and 4a’-d’). A structure for the key intermediate involved in the formation of compounds 3 and 4 has been proposed.

■ Stereospecific Synthesis of trans-1,4-Diphosphacyclohexanes

Yasuhiro Morisaki,* Hiroaki Imoto, Ryosuke Kato, Yuko Ouchi, and Yoshiki Chujo*

*Department of Polymer Chemistr, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan

Abstract

Stereospecific synthesis of trans-1,4-diphosphacyclohexanes via intramolecular oxidative coupling of P-stereogenic bisphosphine borane complexes is reported. Regardless of the enantiopurity of the starting materials, only trans-isomers were formed. The synthesis and characterization of the obtained products are described in detail herein.

■ Errata “Cytotoxic Eunicellin-Type Diterpenes from the Soft Coral Liophyton viscudium”: HETEROCYCLES, 2011, 83, 2149

Tetsuo Iwagawa,* Daiki Kusatsu, Keiko Tsuha, Toshiyuki Hamada, Hiroaki Okamura, Tatsuhiko Furukawa, Shin-ichi Akiyama, Matsumi Doe, Yoshiki Morimoto, Fumihito Iwase, and Kaoru Takemura

*Department of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka Kagoshima 890-8544, Japan

■ Errata “A New Series of Bisbenzimidazole Derivatives: Synthesis, Antitumor Activity and Low Toxicity on PBMC”: HETEROCYCLES, 2012, 85, 2231

Xiu-Jun Wang, Qing-He Wang,* Chao Liu, Wei Li, Jian Wang, Na Yang, and Mao-Sheng Cheng*

*School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China