HETEROCYCLES

■ Contents

■ Efficient Synthesis of Indoles and Benzo[b]furans via [3,3]-Sigmatropic Rearrangement of N-Trifluoroacetylenehydrazines and Enehydroxylamines

Okiko Miyata,* Norihiko Takeda, and Takeaki Naito*

*Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan

Abstract

This review summarizes an efficient synthesis of benzo[b]furans and indoles via [3,3]-sigmatropic rearrangements of N-trifluoroacetyl enehydroxylamines and enehydrazines, which were triggered by acylation of oxime ethers and hydrazines. TFAA and TFAT-DMAP have been proved to be the best reagent to induce [3,3]-sigmatropic rearrangement for the synthesis of benzo[b]furans and indoles. This method was successfully applied to the short synthesis of natural products.

■ Recent Advances in the Total Synthesis of Xanthanolide Sesquiterpenoids

Kozo Shishido*

*Graduate School of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan

Abstract

Recent advances in the total synthesis of xanthanolide/dinorxanthanolide sesquiterpenoids are described. This family of natural products can be divided into two structural classes according to the stereochemistry at C8 of the basic carbon framework, the oxabicyclo[5.3.0]decene core, i.e., the cis- and trans-fused γ-butyrolactone series. This article reviews the successful total syntheses of the five natural products, 8-epi-xanthatin (1) and sundiversifolide (2) (the cis-series), and 11α,13-dihydroxanthatin (3), xanthatin (4) and diversifolide (5) (the trans-series).

■ Synthesis and Structures of New C2-Symmetrical Chiral Macrocycles Containing the Ephedrine Moiety

Yiwen Chen, Mingzhang Gao, Songde Tan, Joseph H. Reibenspies, and Ralph A. Zingaro*

*Department of Chemistry, Texas A & M University, College Station, Texas 77843-3255, U.S.A.

Abstract

Three kinds of novel C2-symmetrical chiral macrocyclic compounds containing an ephedrine moiety have been designed and synthesized; two of their crystal structures have been determined.

■ One-Pot Synthesis of 6-Substituted Amino-2,4-diaminopyrimidine Derivatives Using Ketene Dithioacetals with Amines and Guanidine Carbonate

Miki Hirose, Masayori Hagimori, Yasuhiro Shigemitsu, Naoko Mizuyama, Bo-Cheng Wang, and Yoshinori Tominaga*

*School of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

6-Substituted amino-2,4-diaminopyrimidine derivatives were prepared by one-pot synthesis using ketene dithioacetals, amine compounds, and guanidine carbonate in pyridine. These pyrimidine products displayed blue fluorescence in the solid state.

■ Silica Gel Catalyzed Synthesis of Quinoxaline 1,4-Dioxides under Solvent-Free Conditions Using Microwave Irradiation

Yusuke Sumiyoshi, 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 quinoxaline 1,4-dioxides in solvent-free conditions under microwave irradiation. Heating of various benzofuroxans and β-ketoesters or 1,3-diketones adsorbed on silica gel in a microwave oven for two minutes affords diverse biologically attractive quinoxaline 1,4-dioxides in high to excellent yields. Silica gel functions not only as support using microwave but also as catalyst and dehydration reagent.

■ Preparation of 4-Cyano-3-methyl-1-phenyl-1H-pyrazole-5-(4-bromophenyl)nitrile Imine: Regio- and Stereoselective Synthesis of a New Class of Substituted 3-Pyrazolines and Pyrazoles

Attreyee Mukherjee and Kumar K. Mahalanabis*

*Department of Chemistry, Jadavpur University, Kolkata-700032, India

Abstract

A regio and stereoselective preparation of a new class of substituted 3-pyrazolyl-2-pyrazolines and pyrazoles in good to excellent yields has been developed by reacting 4-cyanopyrazole-5-nitrile imine with dipolarophiles.

■ Novel and Efficient Synthesis of Pyrazolo[3,4-b]pyridin-6-ones or Their Hydrogenated Derivatives through One-Pot Reaction in Ionic Liquid

Xin-Ying Zhang,* Xiao-Yan Li, Xue-Sen Fan,* Xia Wang, Gui-Rong Qu, and Jian-Ji Wang

*College of Chemistry and Environmental Science, Henan Normal University, Xinxiang, 453007, Henan, China

Abstract

Pyrazolo[3,4-b]pyridin-6-ones or their hydrogenated derivatives were obtained selectively and conveniently through one-pot reaction of aldehyde, ethyl cyanoacetate and 5-amino-3-methyl-1-phenylpyrazole in [bmim][BF4] with or without ferric chloride at different temperatures. Advantages of this novel method include high yield, mild conditions, simple procedure and good selectivity. In addition, the ionic liquid used can be easily recovered and effectively reused.

■ A Convenient Route to New Pyrrolo[1,2-c]pyrimidone, Thiazolo[3,4-c]pyrimidone and Pyrimido[4,5-d]pyridazine Derivatives

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

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

Abstract

The utility of versatile, readily accessible ethyl 6-bromomethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3) and ethyl 6-bromomethyl-2-oxo-4-phenyl-1,2-dihydropyrimidine-5-carboxylate (4) in the synthesis of some new pyrimidine, pyrimido[4,5-d]pyridazine, pyrrolo[1,2-c]pyrimidone and thiazolo[3,4-c]pyrimidone derivatives is reported.

■ Structural Modification of Diketo Acid Portion in 1H-Benzylindole Derivatives HIV-1 Integrase Inhibitors

Stefania Ferro,* Sara De Grazia, Laura De Luca, Maria Letizia Barreca, Zeger Debyser, and Alba Chimirri

*Department of Medicinal Chemistry, University of Messina, Viale Annunziata, 98168 Messina, Italy

Abstract

Our previous studies led to discovery of a very potent benzylindoldiketo acid (CHI-1043) acting as HIV-1 integrase strand transfer inhibitor. We herein report the synthesis of new structurally different compounds in which the 1,3-diketo acid moiety has been substituted with other functionalities. The synthesized derivatives were evaluated for their activity on the IN enzyme and in MT-4 cells but only 4-[1-(4-fluorobenzyl)-4-methoxy-1H-indol-3-yl)-3-hydroxyfuran-2(5H)-one (12) was able to strongly inhibit HIV-1 probably by biotransformation into CHI-1043.

■ Synthesis, Fungicidal and Antibacterial Activity of New Pyridazine Derivatives

Henryk Foks,* Krystyna Wisterowicz, Agnieszka Miszke, Kamil Brożewicz, Katarzyna Wiśniewska, and Maria Dąbrowska-Szponar

*Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland

Abstract

Compounds 1 - 3 were obtained in the reaction of 3,6-dichloropyridazines with phenylacetonitriles in the biphasic system - DMSO / 50% NaOH. The chlorine atom was replaced with cycloalkylamino (4 - 13) and hydrazinyl (23, 24) moiety. These last compounds were condensed with aldehydes (25 - 34). Pyridazynylphenylacetonitriles were converted into amides 14 - 18 and thioamides 19 - 22. In compounds 2, 3 the chlorine atom was replaced with thiophenyl (37, 38) and in compound 1 with thioethyl and thiophenyl (35, 36) functional groups. In the reactions of compounds 1, 2 with ammonium polysulfide thioamides with thiol group (39, 40) and chlorine atom (41, 42) were obtained. Compounds 1 – 17, 19 – 43 were screened for antibacterial and fungicidal activities.

■ Synthesis of 4-Substituted 3,5-Dicyano-2,6-piperidinediones Using Lithium Nitride as a Convenient Source of Ammonia

Li qiang Wu,* Chunguang Yang, Liming Yang, and Lijuan Yang

*College of Pharmacy, Xinxiang Medical University, East of JinSui Road, XinXiang City, Henan Province, 453003, China

Abstract

A simple and efficient one-pot synthesis of 4-substituted-3,5-dicyano-2,6-piperidinediones was achieved in good yields via the three-component reaction of aldehyde or ketone, ethyl cyanoacetate, lithium nitride (Li3N) as a convenient source of ammonia in MeOH.

■ Kinetic Study on Huisgen Reaction Catalyzed by Copper(I): Triazol Formation from Water-Soluble Alkyne and Alkyl Azide

Yosuke Kasuga, Mamoru Ito, Wataru Onoda, Yosuke Nakamura, Seiichi Inokuma, Takehisa Matsuda, and Jun Nishimura*

*Department of Chemistry, Gunma University, 1-5-1 Tenjin-cho, Kiryu 376-8515, Japan

Abstract

The kinetics was examined for the copper(I)-catalyzed Huisgen reaction. Despite the complex reaction pathway, it was successfully analyzed by the second-order kinetics with equal amounts of two organic substrates in the presence of 0.1 equivalent of copper catalyst, after dividing the time course into two stages, the early and late ones. Both stages gave almost the same activation parameters. The reaction of water-soluble alkyl azide (1) was 60 times as fast as that of water-soluble aromatic azide (4) at the early stage and surprisingly 822 times after 15 min reaction time at 30 ˚C.

■ Novel Charge-Transfer Chromophores Featuring Imidazole as π-Linkage

Anjan Patel, Filip Bureš,* Miroslav Ludwig, Jiří Kulhánek, Oldřich Pytela, and Aleš Růžička

*Department of Organic Chemistry, Faculty of Chemical Technology, University of Pardubice, nám. Čs. legií 565, Pardubice, CZ-532 10, Czech Republic

Abstract

Overall 21 imidazole-based chromophores have been synthesized and fully characterized. The imidazole core was systematically substituted with donors (NMe2 and OMe) and acceptors (NO2 and CN groups) additionally separated from the imidazole by π-spacers such as 1,4-phenylen, styryl or thiophen-2-yl in order to finely tune their intramolecular charge transition. The target chromophores were further investigated by UV/Vis spectroscopy as potentially NLO-active compounds.

■ The Condensation of (Chlorocarbonyl)phenylketene with 1,3-Dinucleophiles. II. Preparation of 2-Hydroxy-3-phenyl-4H-pyrimido[2,1-b][1,3]benzothiazol-4-ones and Thioxo Dihydro-4,6(1H,5H)-pyrimidinones

Hassan Sheibani* and Mahboobeh Zahedifar

*Department of Chemistry, Shahid Bahonar University of Kerman, Kerman 76169, Iran

Abstract

A simple one-pot and efficient method is described for the synthesis of 2-hydroxy-3-phenyl-4H-pyrimido[2,1-b][1,3]benzothiazol-4-one and thioxodihydro-4,6(1H,5H)-pyrimidinone derivatives via the reaction of (chlorocarbonyl)phenylketene with 1,3-dinucleophiles such as 2-aminobenzothiazoles and N-arylthioureas respectively. This method offers a simple and convenient route to prepare the title compounds in good to excellent yields in a short reaction time.

■ Medicinal Flowers. XXV. Structures of Floratheasaponin J and Chakanoside II from Japanese Tea Flower, Flower Buds of Camellia sinensis

Sachiko Sugimoto, Masayuki Yoshikawa,* Seikou Nakamura, and Hisashi Matsuda

*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Abstract

Following the investigation of floratheasaponins A, B, and C, a new acylated oleanane-type triterpene saponin termed floratheasaponin J and an aromatic glycoside called chakanoside II were isolated from the flower buds of Japanese tea plant (Camellia sinensis). The structures of the new glycosides were determined by chemical and physicochemical evidence.

■ A Convenient One-Pot Synthesis of Arene-Centered Tris(thiazoline) Compounds

Xuhong Lu, Qingqing Qi, Yumei Xiao, Nan Li, and Bin Fu*

*Department of Applied Chemistry, College of Science, China Agriculural University, Beijing, 100094, China

Abstract

A simple and practical one-pot synthesis of novel enantiopure tris(thiazoline) compounds was documented. The desired products were obtained in moderate to good yields through three steps from commercially available 1, 3, 5-benzenetricarboxylic acid or 2, 4, 6-pyridinetricarboxylic acid, and chiral amino alcohols. Only one column chromatographic purification was needed for the three steps.

■ One-Pot Synthesis of 2-Arylimino-2,3-dihydropyrido[3,2-e]-1,3-thiazin-4-ones by the Reaction of Secondary 2-Chloropyridine-3-carboxamides with Aryl Isothiocyanates

Kazuhiro Kobayashi,* Toshihide Komatsu, Daizo Nakamura, and Hisatoshi Konishi

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

Abstract

A very facile method for the synthesis of 2-arylimino-2,3-dihydropyrido[3,2-e]-1,3-thiazin-4-ones has been developed. Thus, secondary 2-chloropyridine-3-carboxamides undergo addition to aromatic isothiocyanates in the presence of sodium hydride, followed by attack of the sulfur atom of the resulting adducts on the 2-position of the pyridine ring, to give the desired products in fair to good yields.

■ A New and Facile Synthesis of Rutaecarpine Alkaloids

Chih-Shone Lee,* Cheng-Kuo Liu, Yen-Yao Cheng, and Che-Ming Teng

*Department of Chemistry, National Sun Yat Sen University, Kaohsiung, 80424, Taiwan, R.O.C.

Abstract

Relevant rutaecarpine analogues (1a-d) have been synthesized efficiently from the ring opened β-carboline derivatives (3a-d) as key intermediates. A unique one-pot reductive-cyclization as key reaction furnished the synthesis of rutaecarpine alkaloids in excellent yields. The key intermediates (3a-d) were prepared from tryptamine following acylation, Bischler-Napieralski cyclization, benzoylation, and oxidative cleavage of the exocyclic double bond. This new synthetic approach provides a facile access to rutaecarpine analogues with potent inhibitory effect on platelet aggregation.