HETEROCYCLES

■ Contents

■ Development of Trialkyl(2-indolyl)borates as Potential Synthetic Intermediates

Minoru Ishikura*

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

This account deals with our investigation of the reaction and synthetic use of indolylborates as versatile synthetic tools; 1) palladium-catalyzed cross-coupling reaction and its use for the synthesis of indole alkaloids and 2) intramolecular alkylmigration in indolylbotrates for the construction of highly elaborate indole derivatives.

■ Synthesis, Properties and Structures of Phosphorus-Nitrogen Heterocycles

Vasile Simulescu,* Eleonora Crasmareanu, and Gheorghe Ilia

*Department of Organic Chemistry, Institute of Chemistry, Timisoara of the Romanian Academy, 24 Mihai Viteazu Bvd., 300223-Timisoara, Romania

Abstract

The synthesis, properties and structures of heterocyclic molecules containing phosphorous and nitrogen are described in this review. A systematic synthesis of a ring compound needs one or more bifunctional starting molecules that react in a special way to form new bonds and to obtain the ring. Oligomers or polymers can be obtained besides other products resulting from leaving groups necessary to form the new bonds. Hydrazine for example is one of the simplest bifunctional compounds that must be able to introduce two vicinal nitrogen atoms into a cycle, as it will be shown further.

■ Synthetic Studies of Lepranthin, a Lichen-Produced Dimeric Macrolide. Stereoselective Synthesis of a Seco-Acid Based on Stereospecific Epoxide-Opening Reactions

Hisashi Takada, Shinji Nagumo,* Eiko Yasui, Megumi Mizukami, and Masaaki Miyashita*

*Department of Applied Chemistry, Faculty of Engineering, Kogakuin University, Nakano 2665-1, Hachioji, Tokyo, 192-0015, Japan

Abstract

The stereoselective synthesis of a seco-acid derivative of lepranthin (1), a lichen-produced unique 16-membered dimeric macrolide, is described wherein all asymmetric carbon centers were constructed in a highly stereoselective manner, respectively, by using different epoxide-opening reactions of the α,β-unsaturated γ,δ-epoxy ester system and an epoxy alcohol derivative as the key steps.

■ The Synthesis of Novel Palladium(II) Carbene Complexes, Azolium Salts and Their Catalytic Properties

Beyhan Yiğit, Murat Yiğit,* İsmail Özdemir, and Engin Çetinkaya

*Department of Chemistry, Faculty of Arts and Sciences, Adıyaman University, 20240 Adıyaman , Turkey

Abstract

Novel three 1,3-bis[2-(N,N’-diisopropylamino)ethyl]imidazolinium, 1,3-bis[2-(N,N’-diisopropylamino)ethyl]benzimidazolium and 1-(2-diisopropyl- aminoethyl)-3-(2-methoxyethyl)benzimidazolium chloride salts (1, 3a-b) and two palladium complex (2, 4) have been prepared and characterized by C, H, N analysis, 1H NMR and 13C NMR and they have been investigated their catalytic activity in the Heck and Suzuki coupling reactions.

■ Investigations into the Nucleophilic meso-Substitution of F-BODIPYs and Improvements to the Synthesis of 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene

Sarah M. Crawford and Alison Thompson*

*Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3, Canada

Abstract

A series of three F-BODIPYs, with varying levels of steric crowding about the meso-position were selected to investigate nucleophilic meso-substitution of F-BODIPYs. The synthesis of one of these F-BODIPYs, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (totally unsubstituted dipyrrin skeleton), was optimized to give higher yields over routine literature procedures. This modified procedure involves oxidation of a dipyrromethane using p-chloranil, instead of DDQ, to give a dipyrrin which is then trapped in situ as its BF2 complex. Nucleophilic meso-alkylation of the series of F-BOIDPYs with n-butyllithium gave meso-butyl F-BODIPYs in moderate to good yields. This work represents a new, synthetically viable method for the synthesis of meso-alkylated F-BODIPYs. Extension of the nucleophilic substitution methodology to meso-arylation was possible. However, the reaction was unselective: substitution at boron, to give the boron-diaryl C-BOIDPYs, occurred preferentially to nucleophilic meso-substitution and thus a mixture of products was obtained.

■ Efficient Synthesis of Functionalized Diazacyclopenta[c]pentalene with Multiple Intermolecular Interactions in Crystal

Konstantin V. Kudryavtsev*

*Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991, Moscow, Russia

Abstract

Atom economic synthesis of functionalized polysubstituted racemic diazacyclopenta[c]pentalene 7 has been developed using sequential organocatalytic 1,3-dipolar cycloaddition of azomethine ylide with maleic anhydride and three successive amide bonds formation induced by interaction of 4-fluorobenzylamine with heterocyclic anhydride 5. Enantiomers of 7 are connected by Cl-π, H···F and C=O···H intermolecular interactions in crystal.

■ Dowex-50W Promoted Friedländer Synthesis of Substituted Quinolines under Solvent-Free Conditions

Huey-Min Wang,* Rei-Sheu Hou, Hau-Dung Du, Iou-Jiun Kang, and Ling-Ching Chen*

*Department of Cosmetic Science, Chung Hwa University of Medical Technology, Department of Chemistry, National Cheng Kung University, Tainan, 701, Taiwan, R.O.C.

Abstract

An efficient method for the synthesis of substituted quinolines using Dowex-50W ion exchange resin as reusable eco-friendly catalyst vai Friedländer annulation under solvent-free conditions is described.

■ Synthesis and Reactions of a New Series of 1,2,4-Triazolo[4,3-c]quinazolines

Kamal F. M. Atta,* Mohamed G. Marei, and Fatma A. M. Mohamed

*Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt

Abstract

3-Ethoxycabonyl-1,2,4-triazolo[4,3-c]quinazoline (2) has been synthesized in excellent yield by the condensation of 4-hydrazinoquinazoline (1) with diethyl oxalate and was converted into 3-carbohydrazide 3. The later product was treated with potassium thiocyanate, phenylisothiocyanate or carbon disulfide followed by reaction with hydrazine hydrate to give the respective new 1,2,4-triazolo[4,3-c]quinazoline derivatives 4, 8 or 12. Dehydrative cyclization of the later compounds with concentrated sulphuric acid, sodium hydroxide, m-bromobenzoic acid, carbon disulfide, oxalic acid, phenacyl bromide or benzoin yielded the target heterocycles namely, 1,3,4-thiadiazole, 1,2,4-triazole, 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole or 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine incorporating 1,2,4-triazolo[4,3-c]quinazoline ring. The structure of the above compounds was confirmed from their spectral characteristics.

■ New Type Indole Diterpene, Eujindoles, from Eupenicillium javanicum

Shou Nakadate, Koohei Nozawa,* Hitoshi Horie, Yuichi Fujii, and Takashi Yaguchi

*School of Pharmaceutical Sciences, Ohu University, 31-1 Misumido, Tomita-machi, Koriyama, Fukushima 963-8611, Japan

Abstract

Two new indole diterpenes, 17-hydroxyeujindole (1) and 17-oxoeujindole (2), were isolated from the extract of Eupenicillium javanicum IFM 59075 (UC62). The structures containing the absolute configuration were determined by spectroscopic methods.

■ Regio-Controlled Synthesis of 1,4-Benzothiazinones

Touria Ghailane, Mohammed Saadouni, Said Boukhris, Nouzha Habbadi, Amina Hassikou, Abdelali Kerbal, Bernard Garrigues, and Abdelaziz Souizi*

*Laboratoire de Synthèse Organique, Organométallique et Théorique, Faculté des Sciences, Université Ibn Tofail, B. P 133-Kénitra, Morocco

Abstract

Regio-controlled cyclization of gem-dicyanoepoxides with 2-aminothiophenol and its hydrochloride to form 1,4-benzothiazine-2-one or 3-one is described. The cyclization is highly regioselective and the reaction of the epoxides with 2-aminothiophenol under neutral reaction condition gave 1,4-benzothiazine-2-one as a sole cyclized product, whereas that with hydrochloride of 2-aminothiophenol afforded 1,4-benzothiazine-3-one predominantly. The regioselectivity resulted from the reaction condition is discussed.

■ A Facile Synthesis of 2-Substituted 2,3-Dihydro-4(1H)-azuleno[1,2-d]pyrimidinones

Dao-Lin Wang,* Yuan-Feng LI, Jiao Xu, Wei Li, Shao-Fei Li, and Li-Nan Lin

*Liaoning Key Laboratory of Synthesis and Application of Functional Compound, College of Chemistry & Chemical Engineering, Bohai University, Jinzhou 121001, China

Abstract

A facile, efficient and novel approach to access 2-substituted 2,3-dihydro-4(1H)-azuleno[2,1-d]pyrimidinones was developed by condensation of methyl 2-amino-3-carbamoylazulene-1-carboxylate with ketones or ary1 aldehydes in the 2,2,2-trifluoroethanol catalyzed by p-toluenesulfonic acid.

■ The Synthesis of Some Derivatives Based on the 4-Benzyl-1H-pyrazole-3,5-diamine Core

Lukáš Jedinák, Vladimír Kryštof, and Petr Cankař*

*Department of Organic Chemistry, Palacký University, Trida Svobody 8, 77146 Olomouc, Czech Republic

Abstract

The three-step synthesis of 4-benzyl-1H-pyrazole-3,5-diamines 2 from commercially available aldehydes 3 is given. The Knoevenagel condensation was utilized to assemble the initial carbon framework, resulting in the benzylidenemalononitriles 4 which were directly transformed by the reduction of the electron deficient C=C bond to benzylmalononitriles 5. Subsequent cycloaddition of hydrazine with 5 afforded the desired pyrazoles 2. Due to the high similarity with 4-arylazo-1H-pyrazole-3,5-diamines, the biological activities of the 4-benzyl-1H-pyrazole-3,5-diamines 2 were evaluated while focusing on the inhibition of cyclin-dependent kinases (CDKs), but no significant results were obtained.

■ Synthesis and Biological Activities of Some N-Acyl-2,6-diaminopyridines and Related Linker Mode Identical Twin Drugs

Nobuko Mibu, Kazumi Yokomizo, Miyuki Saisho, Marumi Oishi, Hatsumi Aki, Takeshi Miyata, and Kunihiro Sumoto*

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

Abstract

In connection with our studies on biologically active compounds in the class of N-acyl-2,6-diaminopyridines, some molecular modifications were attempted. All of the synthesized compounds were evaluated for biological activity with herpes virus type 1 (HSV-1) by a plaque reduction assay. We observed that most of the synthesized derivatives showed no significant anti- HSV-1 activity, but we found that compounds 5 and 6 with a branched long alkyl chain showed high cytotoxicity to Vero cells.