HETEROCYCLES

■ Contents

■ Development of Novel Asymmetric Reactions and Their Application to the Synthesis of Natural Products

Manabu Node,* Tetsuya Kajimoto, and Minoru Ozeki

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

Abstract

Asymmetric Michael addition of zinc enolate to a chiral nitroolefin was improved and the method was applied to the synthesis of (–)-Δ9(12)-Capnellene [(–)-6], (–)-aphanorphine [(–)-7], and (–)-eptazocine [(–)-8]. Whisky lactone (28) was also prepared by taking advantage of tandem Michael addition-MPV-reduction, which was capable of constructing three contiguous chiral centers of 1,3-mercaptoalcohols. In addition, (+)-negamycin [(+)-35] was synthesized by using the Michael addition of a chiral amine [(–)-31] as a key step with the best overall yield and with shortest steps to date. Efficient synthesis of galanthamine [(-)-51] was attained by a novel strategy of remote asymmetric control of intramolecular Michael addition of phenolic hydroxyl group to the dienone moiety. Moreover, epibatidine [(–)-42] was synthesized by using the Diels-Alder reaction, of which the dienophile, chiral allene dicarboxylate, was prepared by asymmetric crystallization. Finally, the first synthesis of naturally occurring form of dichroanal B (71), dichroanone (72), and taiwaniaquinone H (73) were achieved by using intramolecular asymmetric Heck reaction.

■ Recent Progress of New Catalytic Synthetic Methods for Nitrogen Heterocycles Based on Hydrogen Transfer Reactions

Ryohei Yamaguchi,* Ken-ichi Fujita, and Mingwen Zhu

*Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan

Abstract

This review summarizes a variety of synthetic methods for nitrogen heterocycles based on hydrogen transfer reactions catalyzed by transition metals in a past decade. Most of them employ iridium and ruthenium complexes as the catalysts and provide a versatile and environmentally benign synthetic methodology of various nitrogen heterocyclic compounds. Intermolecular cyclization reactions of amines with alcohols afford 5-7 membered alicyclic amines, quinolines, piperazines, indoles, quinoxalines, pyrroles, benzimidazoles, and benzoxazoles. Intramolecular cyclization reactions of amino alcohols give indoles, 1,2,3,4-tetrahydroqunolines, 1,2,3,4-tetrahydroquinoxalines, 3,4-dihydro-2(1H)-quinolinones, and oxindoles. Friedländer-type cyclization reactions provide a convenient route to various quinolines. Finally, cyclization reactions of amines with amines afford quinolines and phenylpyrrolidines.

■ L-Fructo- and D-Psicofuranosylation Reactions Catalyzed by Scandium Triflate

Takashi Yamanoi,* Toshiaki Ishiyama, Yoshiki Oda, Sho Matsuda, and Mikio Watanabe

*The Noguchi Institute, 1-8-1, Kaga, Itabashi-ku, Tokyo 173-0003, Japan

Abstract

This paper describes the formation of L-fructo- and D-psicofuranosidic bonds by the scandium triflate catalyzed glycosidation. The reaction of the benzoylated L-fructofuranosyl acetate with an alcohol in the presence of 5 mol% scandium triflate in toluene at room temperature for 3 h stereoselectively afforded the corresponding α-L-fructofuranoside in good yields. Several α-D-psicofuranosides were predominantly obtained in good yields by the reactions between the benzoylated D-psicofuranosyl acetate and alcohols under similar reaction conditions. This method successfully provided the sucrose mimics composed of D-glucopyranose and L-fructofuranose or D-psicofuranose.

■ Asymmetric Intermolecular N-H Insertion Reaction of Phenyldiazoacetates with Anilines Catalyzed by Achiral Dirhodium(II) Carboxylates and Cinchona Alkaloids

Hiroaki Saito,* Taketo Uchiyama, Muneharu Miyake, Masahiro Anada, Shunichi Hashimoto, Tohru Takabatake, and Shinichi Miyairi

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

Abstract

Asymmetric N–H insertion of phenyldiazoacetates with anilines catalyzed cooperatively by achiral dirhodium(II) carboxylates and cinchona alkaloids is described. A new catalytic system of dirhodium(II) tetrakis(triphenylacetate), Rh2(TPA)4, and dihydrocinchonine provides phenylglycine derivatives in up to 71% ee.

■ Synthesis of Diaza-Analogue of Fluorenone and Spirobifluorene

Guo-Hong Wu, Qian-Cai Liu,* and Jie Tang

*Department of Chemistry, East China Normal University, 3663 Zhongshan RD(N9, Shanghai 200062, China

Abstract

The effective syntheses of diaza-analogue of fluorenone and spirobifluorene with N=N bond has been conducted with the using of ninhydrin and corresponding acetyl derivatives of arenes. Single-crystal X-ray diffraction of 2-(spirobifluoren-2-yl)- 3,4-dizaspirobifluorene (4a) proved the conformation.

■ Regioselective Synthesis of 3-Indolyl(alkoxy)acetates

Oscar R. Suárez-Castillo,* Myriam Meléndez-Rodríguez, Indira C. Cano-Escudero, Sandra Luz De Ita-Gutiérrez, Maricruz Sánchez-Zavala, Martha S. Morales-Ríos, and Pedro Joseph-Nathan

*Área Académica de Química, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma, Hidalgo, 42184, Mexico

Abstract

The regioselective synthesis of N-carbomethoxy-2-alkoxyindolenines and α-alkoxyindoles is reported. Bromination of indole 5 with NBS/AIBN/CCl4 gave α-bromoindole 6 which after treatment with ROH/3Å molecular Sieves afforded (Z-) and (E)-2-alkoxyindolenines 8a-d as the main products, together with minor amounts of α-alkoxyindoles 9a-d. The reversed regioselectivity was achieved in the absence of molecular Sieves to give α-alkoxyindoles 9a-d as the main products, while no traces of Z- or E-8a-d were detected.

■ Synthesis, Spectral Characterization and Antimicrobial Activity of Novel 5-[(Substituted Methyl]-5-oxo-1,3,2λ4,5λ5-dioxaselena Phosphinan-2-ones

S. Subba Reddy, B. Satheesh Krishna, V. Koteswara Rao, and C. Naga Raju*

*Department of Chemistry, Sri Venkateswara University, Tirupati - 517502, India

Abstract

A series of novel 5-[(substituted) methyl]-5-oxo-1,3,2λ4,5λ5-dioxa selenaphosphinan-2-ones (4-17) were successfully synthesized from tris(bromomethyl)phosphine oxide (1) and sodium selenite (2) to form the intermediate(3) which on further treatment with various alcohols/ thiols/ phenols/ aminoacid esters afforded the title compounds (4-17) and their structures were established by multinuclear NMR (1H-, 13C- and 31P-) and mass spectral data. Their antimicrobial activity was evaluated and they exhibited promising antibacterial activity.

■ Geranyl Derivatives of Isoquinoline Alkaloids Show Increased Biological Activities

Yumi Nishiyama, Kinuko Iwasa,* Suguru Okada, Sousuke Takeuchi, Masataka Moriyasu, Miyoko Kamigauchi, Junko Koyama, Atsuko Takeuchi, Harukuni Tokuda, Hye-Sook Kim, Yusuke Wataya, Kazuyoshi Takeda, Yi-Nan Liu, Pei-Chi Wu, Kenneth F. Bastow, Toshiyuki Akiyama, and Kuo-Hsiung Lee

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

Abstract

Three types of isoquinoline alkaloids were tested for antimicrobial, cytotoxic, anti-malarial, anti-oxidant, and anti-HIV activities, as well as inhibitory activity against Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. N- or O-Geranylation contributed to increased potency in four types of activities except anti-HIV and anti-oxidant. Some types of alkaloids may be useful as lead compounds for developing potential chemotherapeutic agents. N,N-Geranylated salsolinol was significantly active in three different assays, antimicrobial, cytotoxic, and EBV-EA, and may be a most useful compound.

■ Palmariols A and B, Two New Chlorinated Dibenzo-α-pyrones from Discomycete Lachnum palmae

Takunori Matsumoto, Tsuyoshi Hosoya, and Hideyuki Shigemori*

*Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

Abstract

Two new chlorinated dibenzo-α-pyrones, palmariols A (1) and B (2), together with alternariol 9-methyl ether (3), were isolated from the mycelial extract of discomycete Lachnum palmae (NRBC-106495), and the structures of 1 and 2 were elucidated using spectroscopic data. Palmariols A (1) and B (2) are rare dizenzo-α-pyrones containing a chlorine. Compounds 1~3 exhibited weak antimicrobial activity against Mucor racemosus and Bacillus subtilis.

■ Synthesis of (3S)-2,5-Diethoxy-3,6-dihydro-3-isopropyl-6-methylsulfanylpyrazines and Stereoselectivity in Alkylation of the Anions

Yoshihide Usami,* Masao Arimoto,* Chisaka Kioka, Masako Yamanaka, Naoko Matsuda, and Hayato Ichikawa

*Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

The introduction of a sulfur function into Schöllkopf’s bislactim ether was carried out to synthesize the diastereomers of (3S)-2,5-diethoxy-3,6-dihydro-3-isopropyl-6-methylsulfanylpyrazine. Stereoselectivity in the alkylation of the anions derived from those compounds was examined as a basic study of the synthesis of chiral α-sulfanylamino acids.

■ Synthesis of 4-Alkylidene-2-(dimethylamino)methyl-4H-3,1-benzoxazines by the Reaction of Alkyl 2-Isocyanophenyl Ketones with Eschenmoser’s Salt

Kazuhiro Kobayashi,* Yuta Okamura, Shuhei Fukamachi, and Hisatoshi Konishi

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

Abstract

4-Alkylidene-2-(dimethylamino)methyl-4H-3,1-benzoxazines could be prepared in one-pot by simply treating alkyl 2-isocyanophenyl ketones with dimethyl(methylene)ammonium iodide (Eschenmoser’s salt) in dichloromethane at 0 ˚C without any catalysts.

■ Antitumoral Alkaloids from Clausena lansium

Wisanu Maneerat and Surat Laphookhieo*

*School of Science, Mae Fah Luang University, 333 Moo 1, Tasud, Muang, Chiang Rai, 57100, Thailand

Abstract

Three new carbazole alkaloids, mafaicheenamine A-C (1-3), along with five know compounds (4-8) were isolated from the twigs of Clausena lansium. All compounds were characterized by the analysis of spectroscopic methods. In addition, the evaluation of antitumoral activity against three human cancer cell lines, KB, MCF-7 and NCI-H187, of compounds 1, 2 and 4-8 were also reported.

■ An Efficient One-Pot and Solvent-Free Synthesis of Chromeno[2,3-d]pyrimidine Derivatives: Microwave Assisted Reaction

Afsaneh Zonouzi,* Mojtaba Biniaz, Roghieh Mirzazadeh, Merzieh Talebi, and Seik Weng Ng

*School of Chemistry, University College of Science, University of Tehran, Tehran 14155-6455, Iran

Abstract

An efficient synthesis of some new chromeno[2,3-d]pyrimidine derivatives has been described by a solvent-free, multi-component reaction in fairly high yields.