HETEROCYCLES

■ Contents

■ Total Synthesis of Tetrahydropyran-Containing Natural Products Exploiting Intramolecular Oxa-Conjugate Cyclization

Haruhiko Fuwa*

*Graduate School of Life Sciences, Tohoku University, 2-1-1, Katahira, Aoba-ku, Sendai, 980-8577, Japan

Abstract

A growing number of tetrahydropyran-containing biologically active substances are being discovered from nature. Intramolecular oxa-conjugate cyclization (IOCC) is known as one of the most powerful methodologies for the stereoselective synthesis of substituted tetrahydropyran derivatives, although there is clearly room for methodological improvement. In this review, we describe our successful total synthesis of tetrahydropyran-containing natural products by exploiting IOCC and the discoveries that we have made during the course of the synthetic campaigns.

■ Bioactive Natural Products from Myxomycetes Having Effects on Signaling Pathways

Masami Ishibashi* and Midori A. Arai

*Department of Natural Products Chemistry, Graduate School of Pharmaceutical Science, Chiba University, 1-8-1 Inohana, Chuo, Chiba, Japan

Abstract

The myxomycetes (true slime molds) are an unusual group of primitive organisms that may be assigned to one of the lowest classes of eukaryotes. We studied the chemical constituents of a laboratory culture of plasmodia as well as field-collected fruit bodies of myxomycetes, and isolated various compounds with unique chemical structures and bioactivities. We recently also performed screening studies of natural products targeting signaling pathways related to basic studies of diseases and life sciences. Among myxomycetes constituents, we found several bioactive compounds that have effects on signaling pathways, including a cycloanthranilylproline with TRAIL resistance-overcoming activity, peptide lactone derivatives with Wnt signal inhibitory activity, a naphthoquinone pigment with Hes1 dimerization inhibition activity, and bisindole alkaloids with hedgehog signal inhibitory activity. Here we describe our recent results of their isolation, structure elucidation, synthesis, and findings in bioactivity studies.

■ Multicomponent Coupling Reaction of Arynes for Construction of Heterocyclic Skeletons

Hiroto Yoshida* and Ken Takaki

*Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi-Hiroshima 739-8527, Japan

Abstract

Recent progress on the multicomponent coupling reactions of arynes, directed toward straightforward construction of heterocyclic skeletons, by use of 2-(trimethylsilyl)aryl triflates as aryne precursors is reviewed.

■ Chiral Synthesis of Iminosugars

Hiroki Takahata*

*Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

An chiral synthesis of iminosugars such as fagomine, 1-deoxynojirimycine, and isofagomine together with their stereoisomers are described.

■ New Triterpenoid Saponins from Stenocereus eruca

Kazutaka Kakuta, Takeshi Koike, Kaoru Kinoshita, Satoru Ito, Kiyotaka Koyama, and Kunio Takahashi*

*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

Eight new triterpenoid saponins, stellatosides C (1), D (2), and E (3), stellatoside B methyl ester (4), stellatoside C methyl ester (5), thurberoside A (6), phillyriside A (7), and treleaseside A (8) were isolated from Stenocereus eruca A. C. Gibson & K. E. Horak (Machaerocereus eruca Br. & R). The structures of these compounds were elucidated on the basis of spectroscopic evidence and their physicochemical properties.

■ Expedient N-Arylation for the Synthesis of 2-Arylamino-3-cyanopyridines Using Ionic Copper(I) Complex as a Catalyst

Min Zhang,* Biao Xiong, Ting Wang, Xiaoting Wang, Fengxia Yan, and Yuqiang Ding*

*School of Chemistry and Materials Engineering, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu Province, 214122, China

Abstract

The N-arylation of 2-amino-3-cyanopyridines is firstly described by using ionic copper(I) complex (Phen)2Cu+BF4- (phen = 1,10-phenanthroline) as an efficient catalyst. The synthetic protocol can be applied to synthesize a wide range of 2-arylamino-3-cyanopyridine products in good to excellent isolated yields. The resulted products are potentially building blocks for further preparation of biologically interesting products or useful ligands for metal catalysis.

■ Synthesis of 5,6-Disubstituted Thieno[2,3-d]pyrimidines from 4-Chloropyrimidines

Kazuhiro Kobayashi,* Teruhiko Suzuki, Taketoshi Kozuki, Naoki Matsumoto, Hidetaka Hiyoshi, and Kazuto Umezu

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

Abstract

Facile reaction sequences for the preparation of 5,6-disubstituted thieno[2,3-d]pyrimidines starting with 4-chloropyrimidines have been developed. 4-Chloro-6-methoxypyrimidines were aroylated at the 5-positions via lithiation with LDA and subsequent treatment with benzaldehyde or N-methoxy-N-methylbenzamides to give aryl(4-chloro-6-methoxypyrimidin-5-yl)methanones. These pyrimidinyl ketones were transformed in one-pot into 5,6-disubstituted 4-methoxythieno[2,3-d]pyrimidines by a successive treatment with sodium sulfide, BrCH2EWGs, and sodium hydride. Lithiation of 4,6-dichloro-2- (methylsulfanyl)pyrimidine at the 5-position was followed by treatment with tertiary formamides to give 4-chloro-6-(dialkylamino)pyrimidine-5-carboxaldehydes, which could be transformed into 5,6-disubstituted 4-(dialkylamino)thieno[2,3-d]pyrimidines via aryl[4-chloro-6-(dialkylamino)pyrimidin-5-yl]methanones using the same one-pot thiophene ring forming sequence.

■ Facile and Efficient Cyclization of Anthranilonitrile to 2,4-Dichloroquinazoline by Bis(trichloromethyl) Carbonate and Catalytic Amount Triphenylphosphine Oxide

Zhenhua Li, Danli Wu, and Weihui Zhong*

*Key Laboratory of Pharmaceutical Engineering of Ministry of Educations, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310014, China

Abstract

2,4-Dichloroquinazolines were synthesized by the cyclization of anthranilonitrile using bis(trichloromethyl) carbonate (BTC) with the aid of catalytic amount of triphenylphosphine oxide (Ph3PO) at 120 °C. This method was also applied to the synthesis of 2,4-dichlorothieno[2,3-d]pyrimidine. The plausible mechanism is presented.

■ Floral Pigments Isolated from the Sky-Blue Flowers of Oxypetalum caeruleum

Norio Saito, Kenjiro Toki, Toshio Honda, and Fumi Tatsuzawa*

*Laboratoryof Olericultural and Floricultural Science, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate 020-8550, Japan

Abstract

Three anthocyanins (pigments 1 - 3) were isolated from the sky-blue flowers of Oxypetalum caeruleum ‘Caerulea’ as the floral anthocyanins. These three anthocyanins were elucidated to be cyanidin 3-O-[2-O-(β-xylopyranosyl)-β-glucopyranoside]-7-O-β-glucopyranoside (1), cyanidin 3-sambubioside (2), and cyanidin 3-O-[2-O-(β-xylopyranosyl)-β- glucopyranoside]-7-O-[6-O-(trans-feruloyl)-β-glucopyranoside] (3), respectively, by chemical and spectroscopic means. Pigment 1 was present in the flowers as a main anthocyanin, and pigment 3 was a new anthocyanin in plants. Three flavonols glycosides were also isolated from these flowers, and identified to be the 3-O-(2-O-(β-xylopyranosyl)-β-glucopyranoside)s of quercetin (pigment 4) and kaempferol (pigment 5) and kaempferol 3-glucoside (pigment 6). Moreover, the bluing effect on the flower color of O. caeruleum ‘Caerulea’ was discussed.

■ Identification of New Polyprenyl Hydroquinone Derivatives from Tropical Marine Sponge lrcinia Ircinia sp.

Hyi-Seung Lee,* Yeon-Ju Lee, Jong Wook Lee, Hee Jae Shin, Jong-Seok Lee, Kil-Nam Kim, Weon-Jong Yoon, Soo-Jin Heo, and Hye-Kyeong Kim*

*Marine Natural Products Laboratory, Korea Ocean Research & Development Institute, Ansan PO Box 29, Ansan 426-744, Korea

Abstract

Chemical investigations of the tropical marine sponge of the genus Ircinia have resulted in the isolation of three new polyprenyl chromenes (1–3), together with known hydroquinone derivatives (4–9). Their structures were elucidated on the basis of mass spectrometry and detailed 2D NMR spectroscopic data. The anti-inflammatory activity of these compounds was evaluated. Compounds 7, 8, and 9 exhibited moderate inhibition of LPS-induced NO production in RAW 264.7 macrophages.

■ Efficient Synthesis of N-Substituted 4-Arylquinoline Derivatives Using ZnCl2 or ZrO2

Afsaneh Zonouzi,* Roghieh Mirzazadeh, Azadeh Peivandi, and Shahrzad Dehdari

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

Abstract

N-Substituted 7,8-dihydro-7,7-dimethyl-4-arylquinolin-5(1H,4H,6H)-ones 4a-l have been reported by one-pot reaction of cinnamaldehyde derivatives, dimedone and various amines in the presence of ZnCl2 or ZrO2 in fairly high yields.

■ Improved Synthesis of 1-Oxo-1,2,3,4-tetrahydroacridine-9-carboxylic Acids from Isatins and 1,3-Cyclohexanedione

Qinghua Lv, Lizhen Fang,* Chenjuan Lu, and Pengfei Wang

*College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China

Abstract

An improved protocol for the preparation of 1-oxo-1,2,3,4-tetrahydroacridine-9-carboxylic acid derivatives via Pfitzinger condensation under acidic conditions is described, it provides a simple one-pot synthetic method for some useful 1-oxo-1,2,3,4-tetrahydroacridine-9-carboxylic acids which could not be synthesized successfully by Pfitzinger reactions under usual conditions using the corresponding isatins and 1,3-diketones. All the synthesized compounds are characterized by spectral data.