HETEROCYCLES

■ Contents

■ Cross-Metathesis Reaction of 1-Allylated β-Carboline and Isoquinoline Derivatives

Kazuhiro Nagata, Takashi Itoh, Hiromi Fukuoka, Shigeru Nakamura, and Akio Ohsawa*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

N-Protected 1-allyl-1,2,3,4-tetrahydro-β-carboline and 1-allyl-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline were subjected to the cross-metathesis reaction with functionalized olefins using second-generation Grubbs catalyst. The products were obtained in moderate to good yield with high (E)-selectivity.

■ Double Diastereoselective Synthesis of syn,syn-Bis(1,2-isoxazolin-5-yl)methanol and syn,syn,syn-1,2-Bis(1,2-isoxazol-5-yl)ethane-1,2-diols: Facile Route for the Synthesis of Polyols

Bum Suk Son, Bo Gan Song, Jung Ki Kim, Min Jung Seo, Zaesung No, and Hyoung Rae Kim*

*Medicinal Science Division, Korea Research Institute of Chemical Technology, P. O. Box 107, Yusong, Taejon 305-600, Korea

Abstract

syn,syn-Bis(1,2-isoxazolin-5-yl)methanols and syn,syn,syn-1,2-bis(1,2-isoxazol-5-yl)ethane-1,2-diols were synthesized from various nitrile oxides with 1,4-pentadien-3-ol and 1,5-hexadiene-3,4-diol respectively in the presence of ethylmagnesium bromide by double diastereoselective 1,3-dipolar cycloaddition reaction. The resulting isoxazolines were converted to the corresponding new polyols by hydrogenolysis with Raney Ni.

■ Synthesis and Conversion of 3-(2-Hydroxythiobenzamido)benzo[b]furans

Detlef Briel

*Institut für Pharmazie, Pharmazeutische Chemie, Universität Leipzig, Brüderstr. 34, D-04103 Leipzig, Germany

Abstract

A simple method for the introduction of a 2-aroylbenzofuran-3-yl residue at the nitrogen atom of 2-hydroxythiobenzamide is described. Thereby N-(2-aroylbenzofuran-3-yl)-2-hydroxythiobenzamides (4) were obtained which undergo an oxygen-sulfur position exchange when they were heated in acetic acid yielding the isomeric N-(2-thioaroylbenzofuran-3-yl)-2-hydroxybenzamides (6).

■ 1,2-Diazetines as Useful Tools for Ring Transformation Reactions with Isothiocyanates – A New Entry to 1,3,4-Thiadiazines

Rainer Beckert,* Jan Fleischhauer, Anja Darsen, Jennie Weston,* Stephan Schenk, Ariadna Batista, Ernst Anders, Helmar Görls, Manfred Döring, Daniela Pufky, and Olaf Walter

*Institute for Organic and Macromolecular Chemistry, Friedrich Schiller University Jena, Lessingstr. 8, D-07743 Jena, Germany

Abstract

1,2-Diazetines (1) can be acylated with isocyanates (2) to give semicyclic urea derivatives (3). In contrast, isothiocyanates (4) react with 1 under mild conditions to furnish new derivatives of 1,3,4-thiadiazine (5). DFT calculations show that two different mechanistic pathways for this ring transformation are possible. N-Acylation is preferred at lower temperatures; whereas an electrocyclic ring opening/cycloaddition process is possible at higher temperatures.

■ Synthesis of Thienobenzofuranquinone Derivatives by Photoinduced and CAN-mediated 3+2-Type Cycloaddition Reactions

Kazuhiro Kobayashi,* Keiichi Yoneda, Kazutaka Hayashi, Osamu Morikawa, and Hisatoshi Konishi

*Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

Photoinduced cycloaddition between ethyl 5-hydroxy-3-methyl-4,7-dioxo-4,7-dihydrobenzo[b]thiophene-2-carboxylate (1a) and alkenes is reported to give ethyl 7-methyl-4,8-dioxo-2,3,4,8-tetrahydrothieno[2,3-f]benzofuran-6-carboxylates (2). Cerium(IV) ammonium nitrate (CAN)-mediated cycloaddition of ethyl 5-hydroxy-4,7-dioxo-4,7-dihydrobenzo[b]thiophene-2-carboxylates (1) to alkenes or phenylacetylene, giving ethyl 4,8-dioxo-4,8-dihydrothieno[2,3-f]benzofuran-6-carboxylate (2 or 4) and ethyl 4,5-dioxo-4,5-dihydrothieno[3,2-g]benzofuran-7-carboxylate derivatives (3 or 5), is also reported.

■ Synthesis of 1,3,8,8a-Tetrahydro-3,8-epoxyazirino[1,2-b]isoquinolines and Their Reactions with Oxygen Nucleophiles

M. José Alves, * Nuno G. Azoia, and A. Gil Fortes

*Chemistry Department, University of Minho, Campus de Gualtar, 4700-320 Braga, Portugal

Abstract

Cycloadditions of 2H-azirines to isobenzofurans is described. The endo and exo products were obtained and were reacted with oxygen nucleophiles. Tetrahydroquinolines or benzofuranols were obtained, usually in excellent yields. Cycloaddition of the less electrophilic azirine (14) was performed at room temperature in the presence of ZnCl₂. The cycloadduct was hydrolysed in the reaction conditions, but dehydration to give back the original cycloadduct was obtained in the presence of 4Å molecular sieves. The structure assigned in the literature to the product of hydrolysis of the cycloadduct (10) was rectified.

■ Convenient Transformation of 3-Alkoxyfurans to 2-Alkoxy-3-furanones or cis-2-Alkoxy-2-butene-1,4-diones with Phenyltrimethylammonium Tribromide

Shinsei Sayama

*Department of Chemistry, Fukushima Medical University, Hikarigaoka, Fukushima, 960-1295, Japan

Abstract

3-Alkoxy-2,5-diphenylfurans and 3-alkoxy-2,4,5-triphenylfurans were converted to 2-alkoxy-3-furanones with phenyltrimethylammonium tribromides(PTAB) in various alcohols at room temperature. The oxidative ring-opening of 3-alkoxy-2,5-diphenylfurans to cis-2-alkoxy-2-butene-1,4-diones was also accomplished with PTAB in DMSO.

■ Synthesis of Spiro-substituted Benzo[c]azepinones

Álmos Gorka, László Hazai, Csaba Szántay Jr., Viktor Háda, Lajos Szabó, and Csaba Szántay*

*Institute for Organic Chemistry, Budapest University of Technology and Economics, H-1111 Budapest, Gellert ter 4, Hungary

Abstract

Benzo[c]azepinones spiro-substituted by cyclohexanone, cyclohexenone and cyclohexadienone rings were synthesized from 2-tetralone via simple and convenient reaction steps.

■ Generation and [2+3] Cycloadditions of a Sulfonylated Thiocarbonyl S-Methanide

Katarzyna Urbaniak, Magdalena Sobieraj, Grzegorz Mloston,* Anthony Linden, and Heinz Heimgartner*

*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland

Abstract

The sulfonylated thiocarbonyl S-methanide (2a) was generated in situ by addition of diazomethane to the C-sulfonylated dithioformate (1a) and subsequent thermal elimination of nitrogen. This 1,3-dipole was intercepted by C,C- and C,S-dipolarophiles. Whereas in the first case the cycloadducts (10) and (11) could be isolated as stable products, the cycloadducts of type (8), which are the proposed products of the reaction with thioketones, underwent a spontaneous rearrangement to give open-chain ketene dithioacetals (5) and (6).

■ Preparation and Properties of Dehydrotrichotomine-type Dyes: A New Near-Infrared Absorbing Indigoid

Hiroyuki Hashimoto, Kimiaki Shiratori, Keitaro Kawakita, Tomoaki Tanaka, Rika Sekine, and Hajime Irikawa*

*Department of Chemistry, Faculty of Science, Shizuoka University, 836 Ohya, Shizuoka 422-8529, Japan

Abstract

Dehydrotrichotomine-type dyes have been prepared from Pechmann dyes and shown to exhibit the λ_max at near-infrared region. The large bathochromic shift (109 nm) caused by introduction of a double bond into the trichotomine-type chromophore suggests that the dehydrotrichotomine-type dyes have a different intrinsic chromophore, and are regarded as a new indigoid.

■ Synthesis of New Ultraviolet Light Absorbers Based on 2-Aryl-2H-benzotriazoles

Aristides G. Koutsimpelis, Constantinos G. Screttas,* and Olga Igglessi-Markopoulou

*Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48, Vas. Constantinou Ave., 116 35 Athens, Greece

Abstract

A procedure for the synthesis of some new ultraviolet absorbers of the benzotriazole series is reported. The compounds bear a carboxylic or a formyl group para to the hydroxy group, and these functionalities impart to the absorbers improved compatibility with certain disperse dyes on polyester fibers.

■ Two New Taxoids from the Needles and Stems of Taxus chinensis

Zhi-Hua Xia, Li-Yan Peng, Rong-Tao Li, Qin-Shi Zhao,* and Han-Dong Sun

*State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Heilongtan, Kunming 650204, Yunnan, China

Abstract

Two new taxoids, named 10-O-benzoyl-15-O-acetyltaxumairol X (1) and 5-O-acetyl-20-O-deacetyl-4,20-p-hydroxylbenzylidenedioxytaxuyunnanine L (2), were isolated from the needles and stems of Taxus chinensis. Their structures were determined on the basis of combined 1D and 2D spectral techniques.

■ Two New Cycloartane Triterpene Glycosides and a New Alkaloid from Souliea vaginata

Liang Zhou, Jun-Shan Yang,* Xia Wu, Jian-Hua Zou, Xu-Dong Xu, and Guang-Zhong Tu

*Institute of Medical Plant Development, Chinese Academy of Medical Sceinces and Peking Union Medical College, Xibei Wang, Hai-Dian District, Beijing 100094, China

Abstract

Chemical investigation on the rhizome of Souliea vaginata resulted in the isolation of two new cycloartane triterpene glycosides and a new alkaloid, soulieosides D and E, and soulieotine (1—3), and their structures were elucidated on the basis of extensive NMR spectral experiments and chemical methods as (20S*,22R*,23S*,24R*)-16β:23;22:25-diepoxy-3β,24-dihydroxy-23-methoxy-9,19-cyclolanostane-3-O-β-D-(4-acetyl)xylopyranoside (1), (20S*,22R*,23S*,24R*)-16β:23;22:25-diepoxy-3β,23,24-trihydroxy-9,19-cyclolanostane-3-O-β-D-(3-acetyl)xylopyranoside (2), E-3-(3’-methyl-2’-butenylidene)-6-methoxy-2-indolinone (3).

■ Multistep Synthesis of Pyrido[3’,2’:4,5]pyrrolo[3,2-d][1,3]oxazin-4(5H)-one from 2-Aminonicotinonitriles

Sribhashyam R. Kanth, Dravidum Maitraie, Ghojala V. Reddy, Banda Narsaiah,* and Pamulaparty S. Rao

*Fluoroorganic Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India

Abstract

Pyrido[3’,2’:4,5]pyrrolo[3,2-d][1,3]oxazin-4(5H)-ones (7) were synthesized starting from 2-aminonicotinonitriles (1) through multistep synthesis involving Sandmeyer reaction, amination, Thorpe-Ziegler reaction, hydrolysis and cyclisation.

■ Reactions of Bis(silyl-substituted) Methyllithium with α-Hydrogen-free Nitriles into 1,3,5-Triazines

Xia Chen, Sheng-Di Bai, Li Wang, and Dian-Sheng Liu*

*School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China

Abstract

Bis(silyl-substituted) methyllithium has been found to catalyze a conversion of α-hydrogen-free nitriles directly to yield 2,4,6-trisubsituted s-triazines. The generally high yields and relatively mild reaction conditions of this procedure suggest an alternative to other aromatic nitrile cyclotrimerization reactions. Silicotropic rearrangements from C to N or N to N and an unusual elimination of LiCR₂R’ (R=SiMe₃, R’=SiMe₂NMe₂) were observed.

■ Isolation and Identification of Potent Stimulatory Allelopathic Substances Exuded from Germinating Burdock (Arctium lappa) Seeds

Keiko Higashinakasu, Kosumi Yamada,* Hideyuki Shigemori, and Koji Hasegawa

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

Abstract

Two stimulatory allelopathic substances, which have a significant promotive activity for the shoot growth of cockscomb (Celosia cristata), were isolated from the exudates of germinating burdock (Arctium lappa) seeds. They were identified to be arctigenic acid and arctigenin by ¹H and ¹³C NMR and EIMS spectra of them, respectively. Both substances showed growth-promoting activity at the concentrations higher than 10 mg/L for the cockscomb growth test. The contents of arctigenic acid and arctigenin were 58.5 and 39.0 mg/L in the exudates of germinating burdock seeds, respectively. These results suggest that arctigenic acid and arctigenin play important roles in the stimulatory allelopathy of burdock seeds during seed germination stage.

■ 1,4,5,6-Tetrahydropyrimidinium Halides Ligands for Suzuki-Miyaura Cross-Coupling of Unactivated Aryl Chlorides

Bülent Alici, Ismail Özdemir,* Nevin Gürbüz, Engin Çetinkaya, and Bekir Çetinkaya

*Department of Chemistry, Faculty of Science and Arts, Inönü University, 44280 Malatya, Turkey

Abstract

Four functionalized bis(1,4,5,6-tetrahyropyrimidinium) salts (2a-d) have been prepared and characterized by conventional spectroscopic methods and elemental analyses. A highly effective, easy to handle and environmentally benign process for palladium mediated Suzuki cross-coupling was developed. The in situ prepared three component system Pd(OAc)₂ / bis(1,4,5,6-tetrahyropyrimidinium) bromides (2a-d) and Cs₂CO₃ catalyses quantitatively the Suzuki cross-coupling of deactivated aryl chloride.

■ Spiroaziridines from 4-Substituted α-Ylidene-γ-butyro Lactones

Tecla Gasperi, M. Antonietta Loreto,* Antonella Migliorini, and Paolo A. Tardella

*Dipartimento di Chimica, Università degli Studi di Roma “La Sapienza”, P. le A. Moro 5, 00185 Rome, Italy

Abstract

4-Substituted α-ylidene-γ-butyrolactones produce N-ethoxycarbonylspiroaziridino γ-lactone diastereomers on treatment with NsONHCO₂Et and CaO. A good stereofacial preference is observed when the ring substituent is a phenyl group. These products are precursors of α-aminolactone as pure diastereomers.

■ An Improved Synthesis of Optically Pure (R)-4-Bromo-N-methyl-1-tosyltryptophan Derivative, a Key Intermediate in the Synthesis of Ergot Alkaloids

Yuusaku Yokoyama,* Ryoko Hara, Nahoko Kato, Yasuoki Murakami, and Hiroaki Okuno

*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

Optically pure (R)-N-Boc- or (R)-Cbz-4-bromo-N-methyl-1-tosyltryptophan methyl ester (11a or b) was synthesized in 2 steps from (R)-N-acetyl-4-bromo-1-tosyltryptophan methyl ester (7) by simultaneous N-methylation and deacetylation using methyl trifluoromethanesulfonate (TfOMe) in the presence of 2,6-di-tert-butyl-4-methylpyridine (DTBMP).

■ Chemoenzymatic Synthesis of Naturally Occurring Phenethyl (1→6)-β-D-Glucopyranosides

Eiji Kawahara, Miho Nishiuchi, Mikio Fujii, Keisuke Kato, Yoshiteru Ida, and Hiroyuki Akita*

*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

Direct β-glucosidation between phenethyl alcohol and D-glucose (5) using the immobilized β-glucosidase from almonds with the synthetic prepolymer ENTP-4000 gave a phenethyl β-D-glucoside (1) in 34% yield. The coupling of the phenethyl O-β-D-glucopyranoside congener (8) and methylthio-2,3,4-tri-O-acetyl-β-D-xylopyranoside (9), 2,3,4-tri-O-acetyl-α-L-arabinopyranosyl bromide (11), and methylthio 2,3,4-tri-O-acetyl-α-L-rhamnopyranoside (13) afforded the coupled products (10, 12, and 14), respectively. Deprotection of the coupled products (10, 12, and 14) afforded the synthetic phenethyl O-β-D-xylopyranosy-(1→6)-β-D-glucopyranoside (2), phenethyl O-α-L-arabinopyranosy-(1→6)-β-D-glucopyranoside (3), and phenethyl O-α-L-rhamnopyranosy-(1→6)-β-D-glucopyranoside (4), respectively.

■ New Nor-neolignan Glycosides from Styrax obassia (Styracaceae)

Takeshi Kinoshita,* Yasuhiro Haga, and Shintaro Narimatsu

*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan

Abstract

Three new nor-neolignan glycosides, named obassiosides A, B and C, along with one known compound egonol-β-gentiobioside were isolated from the bark of Styrax obassia (Styracaceae), and their structures were deduced on the basis of the spectroscopic evidence.

■ Ring Transformation of Dimethoxybenzenes to Heterocycles by Ozonolysis

Yuki Yoshida,* Satoshi Ichikawa, Yuka Shinozuka, Mitsuru Satoh, Kunihiko Mohri, and Kimiaki Isobe

*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

Abstract

Dimethoxybenzene derivatives, which have a hydroxyalkyl or an aminoalkyl side-chain, were oxidized with ozone and transformed to heterocycles by ring closure reaction of the oxidative products.

■ Synthesis of Polynuclear Aromatic Compounds Incorporating a Fused Thiophene Ring

Tarun Kanti Pradhan and Asish De*

*Department of Organic Chemistry, Indian Asociation for the Cultivation of Science, Jadavpur, Calcutta 700 032, India

Abstract

The present review gives an account of the various synthetic routes to polynuclear heteroaromatic compounds incorporating a fused thiophene ring which include analogs of several biologically active compounds. These compounds are synthesized using a suitably functionalised benzo[b]thiophene as the core and applying various annulation reactions. Directed metalation was extensively used both for functionalisation and in annulation reactions.