HETEROCYCLES

■ Contents

■ Total Synthesis and Structure Reinvestigation of So-called Isochimonanthine

Yohei Matsuda, Mariko Kitajima, and Hiromitsu Takayama*

*Graduate School of Pharmaceutical Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

The data for the proposed structure of isochimonanthine, a dimeric pyrrolidinoindoline alkaloid that was synthesized from tryptamine, were not identical with those of the natural product. Careful structure reinvestigation led to the conclusion that the so-called isochimonanthine was a ca. 1:1 mixture of (+)-chimonanthine and meso-chimonanthine.

■ Cu(I)-catalyzed Formation of D-Mannofuranosyl 1,4-Disubstituted 1,2,3-Triazolecarbohybrids

Penny L. Miner, Timothy R. Wagner, and Peter Norris*

*Department of Chemistry, Youngstown State University, 1 University Plaza, Youngstown, OH 44555-3663, U.S.A.

Abstract

2,3:5,6-Di-O-isopropylidene-D-mannofuranose has been exploited as a platform for the synthesis of new 1,2,3-triazolecarbohybrids. Placement of an azide group at C-1 (and C-6) of the carbohydrate allows for reaction with various alkynes in the presence of a Cu(I) catalyst to generate 1,4-disubstituted triazoles regiospecifically. The use of sugar-derived alkynes leads to 1,2,3-triazole-linked di- and trisaccharide carbohybrid analogs with retention of the β-D-manno configuration.

■ Functional 1,3-Benzodioxoles Making a Fluorescent Response to Local Transformation in Chemo-reactive Pendant Groups

Masaya Suzuki, Yoshihiro Nishida,* Yuya Ohguro, and Kazukiyo Kobayashi

*Department of Molecular Design & Engineering, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan

Abstract

From bi-functional methyl 5-nitro-1,3-benzodioxole-4-carboxylates designed as artificial β-amino acid homologues, a series of chemo-functional 5-amide derivatives (acrylamide, maleimide, 4-azidobenzamide and 4-vinylbenzamide) were prepared. These functional compounds were non-fluorescent while they all gave fluorescent products in the corresponding thiol coupling, photo-activated transformation, hydrogenation, and polymerization reations.

■ Synthesis of Functionalized Tetrahydro-β-carboline Derivatives by Modified Pictet-Spengler Reaction

Donghong Li, Yongbin Zhang, Wei Guo,* and Chizhong Xia*

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

Abstract

Instead of iminium salt in Pictet-Spengler reaction, a series of indole-bearing secondary enamines were synthesized through one-carbon unit transfer reactions of a tetrahydrofolate coenzyme models with tryptamine, and applied to Pictet-Spengler reaction. Reaction of the secondary enamines in acid conditions produced a series of functionalized tetrahydro-β-carboline derivatives in good to excellent yields.

■ Preliminary Study of Palladium Catalyzed Iminoannulation in an Imidazo[1,2-a]pyridine Series

Mounir Andaloussi, Jean M. Chezal, Emmanuel Moreau, Claire Lartigue, Anas El Laghdach, Jean C. Teulade, and Olivier Chavignon*

*Laboratoire de Chimie Organique Thérapeutique, Groupe de Recherche en Pharmacochimie, Faculté de Pharmacie, Université de Clermont I, 28, Place Henri Dunant, B.P. 38, 63001 Clermont-Ferrand Cedex, France

Abstract

Palladium-catalyzed iminoannulation was carried out in an imidazo[1,2-a]pyridine (IP) series. tert-Butylimine of 3-haloimidazo[1,2-a]pyridine-2-carbaldehyde reacted with suitably functionalized alkynes in the presence of a catalytic amount of Pd(OAc)₂/PPh₃ and a base to yield dipyrido[1,2-a; 3’,4’-d]imidazoles (5).

■ Reactions of Benzonitrile Oxide with Methoxypyrimidines and Pyrimidones

Antonino Corsaro,* Venerando Pistarà, Antonio Rescifina, Maria A. Chiacchio, Anna Piperno, and Giovanni Romeo

*Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy

Abstract

Methoxypyrimidines preferentially add to benzonitrile oxide to give cycloadducts to their C=N double bonds. These, however, lose benzonitrile affording the corresponding pyrimidones. Cycloadditions to their C=C double bonds take place to a very low extent, and products generally undergo a ring opening process which affords the corresponding oximes. Pyrimidones preferentially give addition products to their nitrogen atoms, and only in the case of 4-pyrimidone, the cycloadduct to its C=C double bond was isolated.

■ Improved Synthesis of (±)-Linderol A and Its First Conversion to (±)-6-epi-Adunctin E

Masayuki Yamashita, Takashi Shimizu, Tomoki Inaba, Ai Takada, Ikuko Takao, Ikuo Kawasaki, and Shunsaku Ohta*

*Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan

Abstract

The synthetic route to a dibenzofuranone (7), a key intermediate of the total synthesis of (±)-linderol A (2), was considerably improved by using a novel stereoconvergent transformation of a cyclobutane (5), and the first synthesis of (±)-6-epi-adunctin E (8) was achieved by application of this route.

■ High-Performance Liquid Chromatographic Enantioseparation Based on Diastereomer Formation with New Fluorescent Chiral Quinoxalines

Akira Katoh,* Ryoji Yamamoto, Takeshi Fujimoto, and Ryota Saito

*Department of Applid Chemistry, Faculty of Engineering, Seikei University, Musashino-shi, Tokyo 180-8633, Japan

Abstract

Two kinds of chiral 2,3-dimorpholinoquinoxalines bearing L-proline and N-bromoacetylproline residues at C-6 position were newly synthesized. The derivatization of (±)-naproxen, (±)-ibuprofen, and (±)-2-phenylpropionic acid with chiral quinoxalines afforded the diastereomers, which emitted an intense fluorescence. All the diastereomers were clearly separated within 16 min on reversed-phase (Finepak SIL C₁₈S) HPLC equipped with a fluorescence detector. The detection limit of the derivatized product was estimated to be 5 pmol/10μL injection volume at S/N=5. Further, the quantum yield of the diastereomer was estimated to be 0.052 by using the relative quantum yield measurement with anthracene as a standard.

■ Synthesis of Polyfused Heterocycle Derivatives Containing the Dipyridoimidazole Core by Friedländer’s Reaction: Access to Analogs of Ellipticine

Nicolas Desbois, Jean-Michel Chezal, Florence Fauvelle, Jean-Claude Debouzy, Claire Lartigue, Alain Gueiffier, Yves Blache, Emmanuel Moreau, Jean-Claude Madelmont, Olivier Chavignon, and Jean-Claude Teulade*

*UMR 484, Inserm UdA-CJP, 28 place H. Dunant, 63001 Clermont-Ferrand, France

Abstract

Reaction of 3-amino-2-formylimidazo[1,2-a]pyridine with various aldehydes and ketones by Friedländer’s methodology afforded an entry to dipyridoimidazole, tri(tetra)azacyclopenta[b]fluorene, tri(tetra)azabenzo[b]fluorene and triazaindeno[2,1-b]phenanthrene derivatives. Intercalation with a synthetic oligodeoxynucleotide was examined.

■ Practical Synthesis of Chiral cis-Cyclohex-4-ene-1,2-dicarboxylic Acid Derivatives by Utilizing (4S)-Isopropyl-1,3-thiazolidine-2-thione

Tinh Van Dang, Motoyuki Miyamoto, Shigeki Sano, Motoo Shiro, and Yoshimitsu Nagao*

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

Abstract

Both enantiomers of chiral cis-cyclohex-4-ene-1,2-dicarboxylic acid derivatives were synthesized by optical resolution of the corresponding enantiomeric mixtures by utilizing (4S)-isopropyl-1,3-thiazolidine-2-thione followed by mild aminolysis, methanolysis, and hydrolysis.

■ A New Synthesis of 2-Substituted 4H-3,1-Benzoxazin-4-ones by Cyanuric Chloride Cyclodehydration of N-Benzoyl- and N-Acylanthranilic Acids

Mohammad S. Khajavi* and Seyed M. Shariat

*Department of Chemistry, Faculty of Science, Shahid Beheshti University, Tehran 1983963113, Iran

Abstract

A new and a convenient method for the synthesis of aryl- and alkyl-2-substituted 4H-3,1-benzoxazin-4-ones by cyclodehydration of N-benzoyl- and N-acylanthranilic acid by cyanuric chloride is described.

■ Synthesis of 2-Pyrones Bridged at the 3- and 6-Positions by Ring-closing Metathesis

Yasuko Morie, Yumiko Suzuki, Kiyoshi Ikeda, and Masayuki Sato*

*School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan

Abstract

Synthesis of 4-hydroxy-2-pyrones bridged at the 3- and 6-positions by ring-closing metathesis was studied. The reaction of 6-(9-decenyl)-4-methoxy-3-(10-undecenoyl)pyran-2-one (6b) by the first generation ruthenium catalyst (7) gave 3,6-bridged 2-pyrone (10b) in 62% yield. The reaction of 3-(6-heptenoyl)-6-(5-hexenyl)-4-methoxypyran-2-one (6a) (n = 4) under the same conditions afforded the 3,6-bridged 2-pyrone (10a) in 6% yield together with considerable amounts of intermolecular metathesis products.

■ A Green Approach to the Synthesis of 2,3-Dihydropyrimidin-2(1H)-ones by Uronium Hydrogensulfate under Solvent-free Conditions

Peyman Salehi,* Minoo Dabiri, Mohammad Ali Zolfigol, and Mostafa Baghbanzadeh

*Department of Phytochemistry, Aromatic and Medicinal Plants and Drug Research Institute, Shahid Beheshti University, Evin, Tehran 1983963113, Iran

Abstract

3,4-Dihydropyrimidin-2(1H)-ones and -thiones are synthesized in high yields by a one-pot condensation of an aldehyde, a β-dicarbonyl compound with hydrogensulfate salt of urea or thiourea under solvent-free conditions.

■ Nitrilimine Cycloadditions to the Cyano Group in Aqueous Media

Giorgio Molteni* and Paola Del Buttero

*Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy

Abstract

Dipolar cycloadditions between nitrilimines (2) and the cyano group of activated nitriles (3) were exploited in aqueous sodium hydrogencarbonate as reaction media in the presence of a surfactant. Short reaction times and mild conditions were experienced affording 1-aryl-5-substituted 1,2,4-triazoles.

■ Four New Coumarin Glucosides from the Roots of Heracleum rapula

Weilie Xiao, Shenghong Li, Yunheng Shen, Xiaoli Li, and Handong 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

Four new coumarin glucosides, 7-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl]demethylsuberosin (1), 8-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyl]-8-hydroxybergapten (2), 8-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranosyl]xanthotoxol (3), and 5-O-[β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl]-8-hydroxybergaptol (4), were isolated from the roots of Heracleum rapula. The structures of these compounds were determined on the basis of their 1D NMR, 2D NMR and HRMS spectral data. Their inhibitory effects on rabbit platelet aggregation respectively induced by PAF, AA and APD were tested. Weak to moderate inhibitory activities for each compound were observed.

■ Two New Steroid Saponins from Paris polyphylla

Yinan Zhang, Feng Yin, and Lihong Hu*

*National Center for Drug Screening, Shanghai Institute of Materia Medica, Graduate School of Chinese Academy of Sciences, 189 Guo-Shou-Jing Road, Shanghai 201203, China

Abstract

Two new steroid saponins (1-2), together with five known compounds (3-7), were isolated from the underground part of Paris polyphylla. They also showed moderate cytotoxic activities against the liver cancer cell line of BEL-7402 in vitro as antineoplastic agents.

■ Synthesis of Benzo[b]naphtho[2,3-d]thiophene-6,11-diones via Palladium(II) Acetate-mediated Cyclization of 3-Arylthio-1,4-naphthoquinone

Chung-Kyu Ryu,* Ik Hwa Choi, Jung Yoon Lee, and Seong Hee Jung

*College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-ku, Seoul 120-750, Korea

Abstract

Palladium(II)-mediated oxidative cyclization of 3-arylthio-1,4-naphthoquinone (4) giving biologically important benzo[b]naphtho[2,3-d]thiophene-6,11-diones (2) has been performed with a stoichiometric amount of palladium(II) acetate in distillated acetic acid.

■ Total Synthesis and Antioxidative Activity of Magnolamide from Magnolia coco

Wen-Fei Chiou, Chien-Chang Shen, Hsi-Jung Yu, Chang-Han Chiang, Ching-Chuan Chen, Wenyi Chang, and Ming-Jaw Don*

*National Research Institute of Chinese Medicine, 155-1, Sec. 2, Li-Nung Street, Taipei 112, Taiwan, R.O.C.

Abstract

A simple total synthesis of naturally occurring magnolamide, N-[4-(2-formyl-5-hydroxymethylpyrrol-1-yl)butyl]-3-(4-hydroxy-3-methoxy- phenyl)-2-propenamide, from pyrrole-2,5-dicarbaldehyde was performed in six steps and its antioxidant activity was compared with probucol and resveratrol. Results showed that magnolamide markedly inhibited CuSO₄-induced oxidation of human low-density lipoprotein (IC₅₀ = 9.7 μM) with similar activity to probucol and resveratrol.

■ Advances on the Chemistry of Furano-diterpenoids from Teucrium Genus

Franco Piozzi,* Maurizio Bruno, Sergio Rosselli, and Antonella Maggio

*Department of Organic Chemistry, Palermo University, Viale delle Scienze, 90128 Palermo, Italy

Abstract

This paper updates the previous reviews, reporting the results published in the last six years on the chemistry of these diterpenoids.