HETEROCYCLES

■ Contents

■ Synthesis of Five- and Six-Membered Heterocyclic Compounds by the Application of the Metathesis Reactions

Krishna C. Majumdar,* Sanjukta Muhuri, Rafique Ul Islam, and Buddhadeb Chattopadhyay

*Department of Chemistry, University of Kalyani, Kalyani 741 235, West Bengal, India

Abstract

This review describes the formation of five- and six-membered heterocyclic rings in various compounds by ring closing diene and enyne metathesis.

■ Cyclo[-His-His-] Derived C2-Symmetric Diketopiperazine as Chiral Ligand for Asymmetric Diels-Alder Reactions

Masahiro Furutani, Seiji Sakamoto, and Kazuaki Kudo*

*Institute of Industrial Science, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8505, Japan

Abstract

A cyclic dipeptide based chiral ligand, cyclo[-His(Tr)-His(Tr)-] (Tr = triphenylmethyl), was designed and prepared through bis-N(τ)-tritylation of two imidazole rings of cyclo[-His-His-]. The complex prepared in situ by mixing Cu(OTf)2 with equimolar amount of this ligand successfully catalyzed asymmetric Diels-Alder reactions in fair to good yields and moderate selectivities.

■ Facile Synthesis of 1-Aryl-2,3-dihydro-1H-isoindoles by Cyclization of N-Formyliminium Ion via Geometrically Disfavored 5-Endo-trig Process

Michikazu Kitabatake, Toshiaki Saitoh, Takehiro Sano, and Yoshie Horiguchi*

*Showa College of Pharmaceutical Sciences, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

Abstract

Synthesis of 1-aryl-2,3-dihydro-1H-isoindoles (isoindolines) (10) was achieved in a highly effective manner via acid catalyzed cyclization of N-formyliminium ion (8) obtained from 2,3-dimethoxybenzylamine and carbonyl compounds with acetic-formic anhydride under a one pot procedure. This Pictet-Spengler type reaction provides a convenient method for preparing 1-arylisoindolines.

■ Regiospecific Synthesis of Unsubstituted Basic Skeletons of Heterocycles Containing Nitrogen Neighboring an Aromatic Ring by the Reductive Ring Expansion Reaction Using Diisobutylaluminum Hydride

Hidetsura Cho,* Yusuke Iwama, Kenji Sugimoto, Eunsang Kwon, and Hidetoshi Tokuyama*

*Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan

Abstract

A systematic investigation of reductive ring expansion reaction of oximes with diisobutylaluminum hydride (DIBAH) was performed. The reaction regiospecifically provided a variety of unsubstituted bicyclic heterocycles 3a-3g or tricyclic heterocycles 3h, 3j-3l that contained nitrogen attached to an aromatic ring.

■ An Efficient Method for the Preparation of New Analogs of Leucettamine B under Solvent-Free Microwave Irradiation

Mansour Debdab, Steven Renault, Samar Eid, Olivier Lozach, Laurent Meijer, François Carreaux,* and Jean Pierre Bazureau*

*Department of Chemistry, University of Rennes 1, Campus de Beaulieu, Avenue du general leclerc, bat. 10A, France

Abstract

A simple and efficient microwave-assisted protocol has been developed for the synthesis of new 2-amino-3,4-dihydro-4H-imidazol-4-one derivatives of leucettamine B. This solvent-free protocol involves sulphur/nitrogen displacement of 2-ethylthio-5-arylidene-imidazolone 5 with a variety of functionalized polar primary amines 6 and this general method afforded a small library of the desired pure products 7a-n in yields ranging from 33 to 92% in moderate reaction times (30-100 minutes).

■ Copper-Mediated N-Arylation in the Synthesis of Aryladenines

Jan Krouželka and Igor Linhart*

*Department of Organic Chemistry, Institute of Chemical Technology Prague, 166 28 Prague, Technická 1905, Czech Republic

Abstract

A series of N3 and N9 aryladenines was prepared by arylation of 8-bromoadenine under modified Chan-Lam-Evans coupling conditions followed by reductive debromination with hydrogen on palladium. Conditions of arylation were optimised to maximise the yield of N3-arylated products. The selectivity of the reaction varied with temperature the ligand used. The best results were obtained in DMF with phenanthroline as a ligand at 60°C.

■ Caprolactam, an Inhibitory Allelochemical Exuded from Germinating Buckwheat (Fagopyrum esculentum) Seeds

Wai Wai Thet Tin,* Hisayoshi Hayashi, Toshihiko Otomatsu, Katsutoshi Hirose, Koji Hasegawa, and Hideyuki Shigemori

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

Abstract

An allelochemical, which showed an inhibiting activity against the radicle growth of cress seeds, was isolated from the exudates of germinating buckwheat seeds. It was identified as caprolactam based on its 1H and 13C NMR spectra. The occurrence of caprolactam in the exudates from seeds of various plant species was studied on the basis of HPLC retention time and its UV spectrum. Caprolactam was detected in the exudates from seeds of sunflower as well as buckwheat, but not in those from seeds of cress, rice, pea, lettuce and radish. The mode of exudation of caprolactam from buckwheat seeds into the culture solution, was studied in relation to seed germination. About 0.8 µg of caprolactam was found in a dry seed. Upon water imbibition for 1 day about 15 % of caprolactam was exuded into the culture solution. The content of caprolactam in an imbibed seed was about 0.69 µg. These results suggest that caprolactam, already presents in dry seeds, was exuded from the seeds into the environment during seed germination stage. Caprolactam inhibited the radicle growth of cress seeds at the concentrations higher than 3 mg/L. All these results suggest that caprolactam may play as an allelochemical in the inhibitory allelopathy of buckwheat seeds during seed germination stage.

■ Synthesis and Retro Aza Diels-Alder Reaction of Some New Isoquinuclidine Derivatives

Liliana Marzorati,* Patrícia Busko Di Vitta, Blanka Wladislaw, Julio Zukerman Schpector, and Claudio Di Vitta*

*Chemistry Institute of the University of São Paulo, Av. Prof. Lineu Prestes 748, 05508-000, São Paulo, Brazil

Abstract

N-Benzyl- and N-(α-methoxycarbonylethyl)-2,4,6-triphenyl-1,2-dihydropyridines were submitted to Diels-Alder reactions with maleic anhydride or N-phenylmaleimide yielding, diastereoselectively, the corresponding endo-anti adducts. These novel isoquinuclidines showed to be resistant to N-alkylation or N-protonation, undergoing an unexpected fragmentation via a retro aza Diels-Alder process.

■ Medicinal Flowers. XXVIII. Structures of Five New Glycosides, Everlastosides A, B, C, D, and E, from the Flowers of Helichrysum arenarium

Li-Bo Wang, Toshio Morikawa, Seikou Nakamura, Kiyofumi Ninomiya, Hisashi Matsuda, Osamu Muraoka, Li-Jun Wu, and Masayuki Yoshikawa*

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

Abstract

Five new glycosides, everlastosides A (1), B (2), C (3), D (4), and E (5), were isolated from the methanolic extract of the flowers of Helichrysum arenarium. Their structures were elucidated on the basis of chemical and physicochemical evidence.

■ Synthesis of Homoproline Analogues Containing Heterocyclic Rings and Their Activity as Organocatalysts for Michael Reaction

Efrosini Barbayianni, Paola Bouzi, Violetta Constantinou-Kokotou, Valentine Ragoussis, and George Kokotos*

*Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Athens 15771, Greece

Abstract

Two homoproline derivatives containing either the 5-thioxo-1,2,4-oxadiazole or the 2-oxo-1,2,3,5-oxathiodiazole bioisosteric groups, in replacement of the carboxyl group, were synthesized and their catalytic activities in Michael reactions were evaluated. The derivative containing the 5-thioxo-1,2,4-oxadiazole ring outperforms proline in the context of enantioselectivity in the reactions between β-nitrostyrene and acetone or cyclohexanone, indicating that the conversion of the carboxylic group of homoproline to a bioisosteric heterocyclic ring leads to a superior organocatalyst.

■ Eremophilane Derivatives from Pittocaulon praecox

Amira Arciniegas,* Ana-L. Pérez-Castorena, Erick Gastélum, José Luis Villaseñor, and Alfonso Romo de Vivar

*Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán 04510, D.F., Mexico

Abstract

Five new compounds; two eremophilane glucosides (1, 2) and three eremophilanolides (3, 11, 12), together with several known compounds were isolated from Pittocaulon praecox. Their structures were elucidated by spectroscopic methods. The anti-inflammatory activity of extracts and main isolated metabolites was evaluated on 2-O-tetradecanoylphorbol-13-acetate (TPA) induced model of acute inflammation.

■ Substituent Effects on Photophysical Properties of N-Thienylcarbazoles

Hideyuki Shimizu, Atsushi Kobayashi, Shingo Itoi, Toshitada Yoshihara, Seiji Tobita, Yosuke Nakamura,* and Jun Nishimura

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

Abstract

The electronic and photophysical properties of a series of N-thienylcarbazoles were first clarified and compared to one another. The characters of both ground and excited states of carbazole moiety are much more affected by a 2-thienyl group than a 3-thienyl group.

■ Synthesis of Quinolizino[3,2-a]quinolizine Derivatives and Their Fluorescence

Kenichirou Yokota, 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

Polycyclic quinolizine derivatives, quinolizino[3,2-a]quinolizines (4a–c), were synthesized in moderate yields by a one-pot method using ketene dithioacetal, methyl bis(methylsulfanyl)methylene-cyanoacetate (2), alkyl 2-pyridylacetates (1a, b), and 2-pyridylacetonitrile (1c). Compounds 4a, b exhibited red fluorescence (Em max: 576 nm) in solid state.

■ Convenient Synthesis of Novel Bis(hydrazone) and Bis(indole) Derivatives

Nabila A. Kheder*

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

Abstract

The synthetic potency of (Z,Z)-3,3'-(ethane-1,2-diyldiimino)-dibut-2-enoate (1) as a versatile precursors for the synthesis of novel bis(hydrazone) and bis(indole) derivatives via its reaction with some electrophiles and nitrogen nuclephiles was investigated.

■ Acyl and Sulfonyl Derivatives of 10-Aminoalkyl-2,7-diazaphenothiazines

Beata Morak-Młodawska and Krystian Pluta*

*Department of Organic Chemistry, The Medical University of Silesia, Jagielloñska Str. 4, 41-200 Sosnowiec, Poland

Abstract

Reaction of 3,3’-dinitro-4,4’-dipyridinyl disulfide (1) with sodium hydroxide in DMF led to 10H-2,7-diazaphenothiazine (4). N-Alkylation of (4) with phthalimidopropyl and phthalimidobutyl bromides gave phthalimidoalkyl derivatives (5) and (6) which were hydrolyzed to aminoalkyldiazaphenothiazines (7) and (8). N-Acylation with acetyl anhydride, benzoyl chloride, ethyl chloroformate and 2-chloroethyl isocyanate gave N-acyl derivatives (9-16). N-Sulfonylation with methanesulfonyl and p-toluenesulfonyl chlorides led to N-sulfonyl derivatives (17-20).

■ New Xanthones from the Barks and Fruits of Cratoxylum cochinchinense

Surat Laphookhieo,* Wisanu Maneerat, Wanwasan Narmdorkmai, and Sorwaporn Koysomboon

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

Abstract

Four new xanthones named cochinxanthone D-G (1, 5, 8, and 9) along with five known xanthones were isolated from the barks and the fruits of Cratoxylum cochinchinense. Extensive 1D, and 2D NMR and other spectroscopic studies were employed to determine the structure of all new compounds.

■ Chemical Constituents and Cytotoxicity from the Stem Bark of Citrus medica

Yu-Yi Chan, Tian-Shung Wu,* and Yao-Haur Kuo

*Department of Chemistry, National Cheng Kung University, 1, Ta-Shiueh Rd., Tainan 70101, Taiwan, R.O.C.

Abstract

A new biscoumarin, namely citrumedin-A [6,6',7,7'-tetramethoxy- 3,3'-biscoumarin] (1), together with twenty two known compounds were isolated from the stem bark of Citrus medica L. var. sarcodactylis Swingle. The structure of this new compound was completely elucidated using a combination of 2D NMR techniques (COSY, NOESY, HMQC and HMBC) and HR-EI-MS analyses. The known compounds were identified by comparison of their spectroscopic and physical data with those reported in the literatures. The isolates were also screened their cytotoxicity against Daoy, Hep2, MCF-7 and Hela cell lines. Lonchocarpol A (12) showed marginally cytotoxic activity against those four cancer cell lines.

■ Studies on the Synthesis and Crystal Structure of N-(1-Naphthyl)succinimide

Ying Wang, Hailong Yang, Hexian Li, and Guochang Wang*

*Institute of Polymer Chemistry, Nankai University, 94 Weijin Road, Tianjin, 300071, China

Abstract

A modified two-step procedure for synthesis of N-(1-naphthyl)succinimide (NaS) was developed, and its single crystal was prepared for the first time. The molecular and crystal structures were characterized by XRD, FT-IR, 1H NMR, DSC, etc. It has been found that the melting point (159-160.5 °C) of our product is ca 10 °C higher than the documented values, while the characteristic infrared absorption band of carbonyl group splits into two peaks (1705cm-1/1779cm-1) rather than one as reported in the references. These discrepancies were further examined by X-ray crystallographic analysis. Meanwhile, photophysical spectroscopy was found to be powerful to study the molecular structure and crystal morphology of organic compound.