HETEROCYCLES

■ Contents

■ Tandem Reactions Initiated by the Conjugate Addition of Chalcogen Compounds ― Utilization and Synthesis of Heterocycles ―

Tadashi Kataoka and Shin-ichi Watanabe*

*College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya 463-8521, Japan

Abstract

Alkynyl- and alkenylselenonium salts reacted with nucleophiles at the α- or β-carbon depending upon the nucleophiles. The α-attack caused the addition-elimination reaction; i.e., the apparent substitution reaction and the β-attack (the conjugate addition) generated an ylide, which brought about the tandem reaction to form a variety of heterocyclic compounds. Some new reactions proceeded via the selenuranes formed by the attack of a nucleophile on the positively charged selenium atom.
An interesting tandem Michael-aldol reaction of enones (ynones) bearing a chalcogenide or a thioamide was developed. The reactions of the 1-[2-(methylchalcogeno)phenyl]propenones gave α-(α-hydroxyalkyl)enones (Morita-Baylis-Hillman adducts) after a work-up with Et3N. The reactions of the 3-cinnamoyl-1,3-oxazolidine-2-thiones with aldehydes gave tricyclic compounds with a bridgehead bound to four heteroatoms. The asymmetric reactions simultaneously induced four stereocenters, three of which are contiguous. Removal of the chiral auxiliary provided 1,3-diols bearing three consecutive stereocenters.

■ Synthesis and Biological Activity of Lamellarin Alkaloids: An Overview

Tsutomu Fukuda, Fumito Ishibashi, and Masatomo Iwao*

*Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

Lamellarins are natural products isolated from marine invertebrates having a unique heterocyclic ring system. Many of these natural products exhibit potentially useful biological activities such as antitumor and anti-HIV activities. In this review, we summarized the synthesis and biological activity of naturally occurring lamellarins and their analogues.

■ Molecular Sieves Catalyzed Synthesis of Phenazine 5,10-Dioxides under Solvent-Free Conditions Using Microwave Irradiation

Saeka Takeuchi, Hiroaki Saito, Shinichi Miyairi, and Tohru Takabatake*

*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan

Abstract

We report on the simple and quick synthesis of phenazine 5,10-dioxides in solvent-free conditions under microwave irradiation. Heating of benzofuroxan and dihydroxybenzene derivatives adsorbed on molecular sieves in a microwave oven for 30 seconds affords diverse biologically attractive phenazine 5,10-dioxides derivatives. Molecular sieves functions not only as support using microwave but also as catalyst and dehydration reagent. Synthesis of phenazine 5,10-dioxides seems to proceed on molecular sieves, not in molecular sieves.

■ One-Pot Chemoselective Synthesis of Different Pyrano-Pyrazole Derivatives

Majid M. Heravi,* Mina Saeedi, Yahya S. Beheshtiha, and Hossein A. Oskooie

*Department of Chemistry, School of Sciences, Alzahra University, Vanak, Tehran, Iran

Abstract

One-pot chemoselective synthesis of different pyrano-pyrazole derivatives has been reported via two different conditions.

■ Palladium-Catalyzed Amination of 2-Chloro-1-azaazulene with 2-Aminopyridine

Mitsunori Oda,* Daisuke Miyawaki, Naoko Matsumoto, and Shigeyasu Kuroda

*Department of Chemistry, Faculty of Science, Shinshu University, Asahi, Matsumoto 390-8621, Japan

Abstract

Palladium-catalyzed amination of 2-chloro-1-azaazulene with 2-aminopyridine was studied under various conditions in order to obtain N-(1-azaazulen-2-yl)-N-(2-pyridyl)amine (4) and N,N-bis(1-azaazulen-2-yl)-N-(2-pyridyl)amine (5) as a multidentate ligand. Results of the reaction and physical and chemical properties of 4 and 5 are described.

■ Friedel-Crafts Reactions of Vinylaziridine Linked to an Ester Group

Hisashi Takada, Eiko Yasui, Yui Sahara, Yūki Chinen, Hirotoshi Tanaka, Yusuke Morita, Chihiro Kobiki, Daiki Narisawa, Megumi Mizukami, Masaaki Miyashita, and Shinji Nagumo*

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

Abstract

Intermolecular Friedel-Crafts reactions of vinylaziridines 11, 12, 15, 16 and 20 linked to an ester with various benzene derivatives occurred at the C4 position selectively to afford 5-amino-4-aryl-2-hexenoate derivatives in good yields.

■ Resveratrol Dimers with an Oxabicyclo Ring in Vatica albiramis

Naohito Abe, Tetsuro Ito, Masayoshi Oyama, Ryuichi Sawa, Yoshikazu Takahashi, and Munekazu Iinuma*

*Laboratory of Pharmacognosy, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan

Abstract

Investigation of the chemical constituents in the stem of Vatica albiramis (Dipterocarpaceae) resulted in the isolation of six stilbenoid derivatives, albiraminols C (1) and D (5), vatalbinosides G (2)–I (4), and J (6). We determined their structures by spectroscopic analysis including two- dimensional NMR, comparison of the NMR data based on isomerism, and computer-aided molecular modeling. Compounds 1–5 had two resveratrol units and are the first instance of resveratrol derivatives bearing an oxabicyclo[3.2.2]nonadiene ring system. Compound 6 is the oxidative product of 2 bearing a carbonyl group.

■ Synthesis of Demethoxy-Lycoraminone

Klára Herke, László Hazai, Zsófia Dubrovay, Viktor Háda, Zsuzsanna Sánta, Csaba Szántay, Jr., György Kalaus, and Csaba Szántay*

*Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, H-1525 Budpest II, Pusztaszeri ut 59-67, P.O. Box 17, Hungary

Abstract

Demethoxy-lycoraminone (8) was prepared in several steps starting from the appropriate benzo[c]azepine dione derivative (9). Ketone (9) was protected as a ketal group followed by methylation on the azepine nitrogen atom. After reduction of the imide carbonyl groups, deprotection, demethylation and ring closure were carried out as a one-pot reaction in methanesulfonic acid in the presence of racemic methionine.

■ Synthesis and Transformations of Novel Benzo[c]furans

Roberta Palkó, Zsuzsanna Riedl, Sándor Sólyom, István Pallagi, Tibor András Rokob, Orsolya Egyed, and György Hajós*

*Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, H-1025 Budpest, Pusztaszeri út 59, P.O. Box 17, Hungary

Abstract

Some novel 1-cyanoisobenzofurans have been synthesized by a convenient ring closure methodology. The new products easily reacted with electron-deficient olefins and acetylenes to yield Diels-Alder products. Theoretical calculations satisfactorily support the quinonoide character of the new isobenzofuran derivatives.

■ Synthesis and Antimicrobial Evaluation of Some New Tetrahydropyrimidine Derivatives

Yahia N. Mabkhot, Nabila A. Kheder,* and Ahmad M. Farag

*Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt

Abstract

The utility of 1,2,3,4-tetrahydropyrimidine-5-carboxylate (1a,b), and 1,2-dihydropyrimidine-5-carboxylate (2) in the synthesis of some new functionalized pyrimidine derivatives such as 6-(2-(dimethylamino)vinyl)-1,2,3,4-tetrahydropyrimidine, 6-(1-cyano-2-(phenylamino)-2-thioxoethyl)-1,2,3,4-tetra-hydropyrimidine and 4,6-distyryl-1,2-dihydropyrimidine derivatives is reported. Antimicrobial evaluation of some selected examples from the synthesized products was carried out and showed promising results.

■ Photochemical Reaction of 4,7-Dimethylbenzofurazan Using Laser

Akira Mori, Yoshiteru Mikami, Hiroaki Saito, Koji Kobayashi, Shinichi Miyairi, Hisashi Ohshima, and Tohru Takabatake*

*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan

Abstract

4,7-Dimethylbenzofurazan 1 was more reactive than other dimethylbenzofurazans, methylbenzofurazans and benzofurazan for short duration irradiation using a Xe lamp (Pyrex filter). Compound 1 was transformed by irradiation with the third harmonic of a Quanta-Ray Nd:YAG laser (355 nm) into (2Z,4Z)-2,5-dimethylhexa-2,4-dienedinitrile monoxide 2 in CDCl3 at room temperature in excellent yield. With increasing temperature, the isomeric opened form compound 2 is thought to be thermally reverted to the original benzofurazan structure. The rate constant for this recyclization of 2 to 1 using CHCl3 at 293 K was 1.16 x 10-5 s-1. Irradiation of 1 in CDCl3 yields photoproduct compound 2 with a quantum yield of 0.48, and a chemical yield of 99%. The yield of this photoreaction was dependant on the laser power and exposure time.

■ Silyl Nitronate 1,3-Dipolar Cycloaddition Reactions with meso-Tetraarylporphyrins

Mothi M. Ebrahim, Maxime Moreau, and Mathias O. Senge*

*School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity College Dublin, Dublin 2, Ireland

Abstract

Isoxazoline-fused chlorins were obtained in moderate yields from the reaction of silyl nitronates and 5,10,15,20-tetra(pentafluorophenyl)porphyrin in toluene at 85 °C.

■ Phloroglucinols from the Leaves of Eucalyptus globulus

Tetsuro Kawabata, Tatsuya Hasegawa, Yuka Nojiri, Chiaki Uchida, Tomoyuki Tsubata, Hikaru Kato, Fumihide Takano, and Tomihisa Ohta*

*Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

A new acylphloroglucinol sesquiterpene structure, euglobal-IX (1), together with five known compounds, euglobal-III (2), -IVa (3), -IVb (4), -Ia2 (5) and robustadial B (6), were isolated from the leaves of Eucalyptus globulus extracted with methanol or methanolic ethylacetate. The chemical structure and relative configuration of 1 was determined by 1D, 2D NMR and MS spectroscopic analyses. New acylphloroglucinol 1 inhibited the catalytic activity of CYP3A4 (IC50 = 38.8 μM).