HETEROCYCLES

■ Contents

■ New Developments in the Synthesis of Saccharin Related Five- and Six-Membered Benzosultams

Zhaopeng Liu* and Yoshio Takeuchi

*Department of Organic Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44, WenHua XiLu, Jinan 250012, China

Abstract

Recent developments in the novel synthesis of saccharin related five- and six-membered benzosultams are reviewed.

■ The Diterpenoids from the Genus Hyptis (Lamiaceae)

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

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

Abstract

The genus Hyptis (family Lamiaceae) is known mainly for the essential oils isolated from the aerial parts of several species. Less known are the diterpenoids, extracted from a limited number of species. In consideration of the interest for the structures of this class of compounds, largely occurring in the whole Lamiaceae family, the present paper means to review and update their chemistry. Also the use of many species of Hyptis in folk-medicine is reported.

■ Novel Application of an Electrooxidative Method for the Formation of a Tetrahydrofuran Ring from 5-Hydroxy-2-pentanone Phenylhydrazone

Mitsuhiro Okimoto,* Takashi Yoshida, Masayuki Hoshi, Kazuyuki Hattori, Masashi Komata, and Tomohito Chiba

*Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, Koen-cho 165, Kitami, Hokkaido 090-8507, Japan

Abstract

Various ketone phenylhydrazones that possess a hydroxy group on the parent ketone moiety were subjected to electrooxidation in methanol in the presence of KI and NaOMe. In the case of 4-hydroxy-2-butanone phenylhydrazone, the nucleophilic attack of the azomethine carbon by a methoxide ion affording the corresponding methoxy(phenylazo)alcohol was dominant. Interestingly, however, in the case of 5-hydroxy-2-pentanone phenylhydrazone, similar reaction conditions favored the intramolecular cyclization to afford a (phenylazo)tetrahydrofuran derivative.

■ Lossen-Type Rearrangement Products in the Reaction of N-(Phthalimidoyloxy)-3-phenylpropionate and -tosylate with Benzyl Alcohol

Shunsuke Takagi, Md. Chanmiya Sheikh, Asako Ogasawara, Masayuki Ohira, Hitoshi Abe, and Hiroyuki Morita*

*Department of Material Systems Engineering and Life Science, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

This paper reports the reaction of N-(phthalimidoyloxy)-3-phenylpropionate (2a) and -tosylate (6) with benzyl alcohol as a nucleophile to afford the products via Lossen-type rearrangement. To study the scope of this reaction mechanism, we also studied the reaction of several N-sulfonyloxyimide derivatives with benzyl alcohol under similar conditions and found that the same types of products were obtained in high yields.

■ Synthesis of (–)-Heliannuol E via Mercuric Triflate Catalyzed Arylene Cyclization

Tomoyo Kamei, Tamiko Takahashi, Masahiro Yoshida, and Kozo Shishido*

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

Abstract

The third-generation synthesis of (–)-heliannuol E has been accomplished employing mercuric triflate catalyzed arylene cyclization as the key step.

■ Convenient Synthesis of Novel Nitrones: (Z)-4-Amino-5-hydroxyimino-2,5-dihydro-1H-imidazole 3-Oxides

Xue-Qin Cao, Zhan-Xiong Li, Wen-Xing Zhong, Li-Hua Qiu, and Guo-Qiang Chen*

*College of Textile and Clothing Engineering, Soochow University, 178#, Ganjiang East Road, Suzhou, Jiangsu 215021, China

Abstract

Highly functionalized derivatives of (Z)-4-amino-5-(hydroxyimino)-2,5-dihydro-1H-imidazole 3-oxide were first and conveniently synthesized by the reactions of 3,4-diaminoglyoxime with benzaldehyde derivatives in the presence of p-toluenesulfonic acid. The procedure represents an effective method to obtain a new kind of nitrones.

■ New Cytotoxic Nor- and Bisnorditerpene Dilactones, Makilactones A-D, from Podocarpus macrophyllus D. Don

Kimihiko Sato, Keito Sugawara, Hirono Takeuchi, Hyun-Sun Park, Toshiyuki Akiyama, Tetsuo Koyama, Haruhiko Fukaya, Yutaka Aoyagi, and Koichi Takeya*

*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

Four new nor- and bisnorditerpene dilactones, makilactones A-D, were isolated from a MeOH extract of bark and root of Podocarpus macrophyllus D. Don (Podocarpaceae) with three known diterpene dilactones. The structures of the new nor- and bisnorditerpene dilactones having a 7:8, 9:11-dienolide moiety were determined by the spectroscopic studies, including 1D and 2D NMR spectral analysis, and single crystal X-Ray crystallographic analysis. Two of the presently isolated compounds were shown to be very strongly cytotoxic.

■ Synthesis of Indolylindolines Mediated by tert-BuNH2

Oscar R. Suárez-Castillo,* Myriam Meléndez-Rodríguez, Ana L. Morales-García, Indira C. Cano-Escudero, Yaneth M. A. Contreras-Martínez, 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

An improved synthesis of N1-carbomethoxylated indolylindolines 2 from 5-substituted indoles 1, by replacing the previously employed strong acids or toxic metals with t-BuNH2/MeOCOCl in CH2Cl2/H2O, is described. The substituent effect of electron donor or acceptor groups was examined, revealing that electron-deficient indoles are less reactive to dimerization than electron-rich indoles, with 5-cyano and 5-nitroindoles leading to no reaction. A dynamic process caused by the restricted rotation of the N-CO2Me bond of 2 was evidenced by 1H NMR measurements.

■ Diketopiperazine Supramolecule Derived from Hydroxyphenylglycine

Yosuke Ohta, Kayo Terada, Toshio Masuda, and Fumio Sanda*

*Department of Polymer Chemistr, Graduate School of Engineering, Kyoto University, Kyoudai-katsura, Nishikyo, Kyoto 615-8510, Japan

Abstract

A diketopiperazine (DKP) having long alkyl chains was synthesized from D-p-hydroxyphenylglycine, and the formation of supramolecules was examined. The 1H NMR and UV-vis spectroscopic measurements and molecular modeling have suggested that the DKP molecules are aligned based on hydrogen bonding between the amide groups, and there is no stacking between the phenyl groups.

■ Role of 2-Naphthyl Ether Intermediate in Formation of Isolable Atropisomers Derived from the Coupling Reaction of (2-Hydroxy-3,3-dimethylindolin-1-yl)(substituted Phenyl)methanones with 2-Naphthol

Masashi Eto, Fumikazu Ito, Hidetoshi Sato, Itaru Shinohara, Koki Yamaguchi, Yasuyuki Yoshitake, and Kazunobu Harano*

*Laboratory of Molecular Design, Sojo University, 4-22-1, Ikeda, Kumamoto-shi, 860-0082, Japan

Abstract

The formation pathway of the atropisomers derived from the reaction of (2-hydroxy-3,3-dimethylindolin-1-yl)(4-substituted phenyl) methanones with 2-naphthol in the presence of BF3•Et2O was discussed on the basis of the isolation of the 2-naphthyl ether intermediate whose structure was determined by single crystal X-ray analysis. The results indicate that the coupling reaction proceeds through stepwise mechanism, i.e., the ether intermediate formation followed by Fries-type rearrangement.

■ Isolation of β-Sitosterol and Digalactopyranosyl-diacylglyceride from Citrus hystrix, a Thai Traditional Herb, as Pancreatic Lipase Inhibitors

Daisuke Watanabe, Rie Kerakawati, Tetsuo Morita, Tomonori Nakamura, Koichi Ueno, Takuya Kumamoto, Waka Nakanishi, Tsutomu Ishikawa,* Jun Uzawa, Hiroko Seki, Masahiko Tachi, Ken-ichi Harada, Yoshinori Higuchi, and Chaiyo Chaichantipyuth

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

Abstract

β-Sitosterol and 3-[O-α-galactopyranosyl-(1”→6’)-O-β-galactopyranosyl]-1-O-linolenyl-2-O-palmitylglyceride were isolated from the leaves of Citrus hystrix, a Thai traditional herb, as pancreatic lipase inhibitors.

■ A Facile Access for Synthesis of Novel Isoquinoline-Based Heterocycles

Hamdi M. Hassaneen,* Tayseer A. Abdallah,* and Enas M. Awad

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

Abstract

Hydrazonoyl halides 2, 7 and 12 react with alkyl 2-(3,4-dihydro-6,7-dimethoxy-2H-isoquinoline-1-ylidene)carboxylate 1 to give 4-(3,4-dihydro-6,7-dimethoxy-2H-isoquinoline-1-ylidene)-2,5-diaryl-2,4-dihydropyrazol-3-one 6, alkyl 2-arylazo-5,6-dihydro-8,9-dimethoxy-3-alkyl(or aryl)pyrrolo[2,1-a]isoquin-oline-1-carboxylate 10 and alkyl 2-(2-arylhydrazono)-2,3,5,6-tetrahydro-8,9-dimethoxy-3-oxopyrrolo[2,1-a]isoquinoline-1-carboxylate 15, respectively. The structures of the new compounds were elucidated on the basis of elemental analyses, spectral data and X-ray crystallographic analyses.

■ Structure and Conformation of Photosynthetic Pigments and Related Compounds. 13. Identification of Localized Vibrational Modes in Chlorophyll A Derivatives

Mathias O. Senge*

*School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity College Dublin, Dublin 2, Ireland

Abstract

A Resonance Raman investigation of chlorophyll a and meso-chlorinated and ring V hydroxylated derivatives and pheophytins reveals localized vibrational modes in the chlorophyll series. Both chlorination and hydroxylation give rise to changes in both band intensity and frequency throughout the spectrum. Chlorination affects mainly the core sensitive bands with CaCm and CaN character. Hydroxylation leads to changes in the carbonyl and ring V associated bands. Small, but real spectral differences were found between the 10-epimers.

■ Tetrahydropyrimidine Derivatives as Efficient Organic Reductants for Transfer Hydrogenation

Yongbin Zhang, Guofu Zhou, and Wei Guo*

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

Abstract

Two six-membered heterocyclic organic reductants, 1-acetyl-2,3-dimethyltetrahydropyrimidine (ADMP) and 1-tosyl-2,3-dimethyltetrahydropyrimidine (TDMP), were designed and synthesized for transfer hydrogenation. It was shown that both the two reductants could directly reduce a variety of aldehydes and imines to the corresponding saturated products in good yields.

■ Thermal Decomposition of N-Alkylated 2-Aminobenzophenones

Evelyn Cuevas Creencia,* Atsushi Takahashi, and Takaaki Horaguchi*

*Department of Chemistry, College of Science and Mathematics, MSU-Iligan Institute of Technology, Iligan City 9200, Philippines

Abstract

Thermal decomposition of N-alkylated 2-aminobenzophenones 1a-d was studied at 400-560 °C, using calcium oxide as catalyst. The reactions yielded both 5- and 6-membered heterocyclic compounds. The N-methylated-2-aminobenzophenones 1a-b decomposed at 400-560 °C to give 2-phenylindole 2 (47% at 500 °C from 1b), acridine 4 and phenanthridine 5, while the N-benzylated-2-aminobenzophenones 1c-d decomposed at 400-560 °C to give 2,3-diphenylindole 3 (33% at 450 °C and 400 °C from 1c and 1d, respectively), acridine 4 and phenanthridine 5.

■ Scyphiphorins C and D, Two New Iridoid Glycosides from the Chinese Mangrove Scyphiphora hydrophyllacea

Shu-Hong Tao, Shu-Hua Qi, Si Zhang,* Zhi-Hui Xiao, and Qing-Xin Li

*Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China

Abstract

Two new iridoid glycosides with a lignan substituent, named scyphiphorins C (1) and D (2), were isolated from the stem bark of a Chinese mangrove Scyphiphora hydrophyllacea Gaertn. f., together with five known iridoid glycosides, 10-O-acetylgeniposidic acid (3), 7-deoxy-8-epi-loganic acid (4), mussaenoside (5), 7-deoxygardoside (6), and 10-deoxygeniposidic acid (7). The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic data, especially 2D NMR techniques.

■ Rumphellolide H, a New Natural Caryophyllane from the Gorgonian Rumphella antipathies

Tsong-Long Hwang, Yin-Di Su, Wan-Ping Hu, Li-Fan Chuang, and Ping-Jyun Sung*

* , National Museum of Marine Biology and Aquarium, 2 Houwan Road, Checheng, Pingtung, Taiwan 944, Taiwan, R.O.C.

Abstract

A new natural caryophyllane-type sesquiterpenoid, rumphellolide H (1), which possesses a tetrahydropyran moiety in structure, was isolated from the gorgonian coral Rumphella antipathies. The structure of 1 was established by spectral data analysis and this metabolite showed moderate inhibitory effects on elastase release by human neutrophils.

■ A Facile and Convenient Method to the One-Pot Synthesis of 2-Mercapto-4(3H)-quinazolinones

Farzad Nikpour,* Roya Mozafari, and Touraj Paibast

*Department of Chemistry, Faculty of Sciences, University of Kurdistan, Sanandaj, Pasdaran Bivd., P.O.Box 66135-416, Iran

Abstract

A facile and convenient method to the one-pot synthesis of 2-mercapto-4(3H)-quinazolinones is described from the reaction of anthranilic acid derivatives with thiourea in PEG.

■ Synthesis and Properties of 9,9’-Spirobifluorene-Based Heterocycles

Jong Myoung Chea and Yurngdong Jahng*

*College of Pharmacy, Yeungnam University, Kyongsan 712-749, Korea

Abstract

A series of 9,9’-spirobifluorene-derived N-heterocycles were prepared by Frieländer reaction of 2-acetyl-9,9’-spirobifluorene with a series of ortho-aminoaldehydes in 74-88% yields. Spectral properties and abilities to form Ru(II) complexes were examined.

■ Studies of Traditional Folk Medicines in Xinjiang Uighur Autonomous. II. Research for Chemical Constituents of Xinjiang Licorice

Noriaki Iwasaki, Masaki Baba,* Halisha Aishan, Yoshihito Okada, and Toru Okuyama

*Natural Medicine and Phytochemistry, Meiji Pharmaceutical Uni1versity, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A new chromene, 5-[2-(4-hydroxyphenyl)ethyl]-2,2-dimethyl-7-[(3- methyl-2-butenyl)oxy]chromene, named xinjiastilbene A (1), a new benzofuran, 4-[2-(4-hydroxyphenyl)ethyl]-6-[(3-methyl-2-butenyl)oxy]benzofuran, named xinjiastilbene B (2), and a chalcone, 4'-hydroxy-2-methoxy-4-prenyloxy-chalcone, named xinjiachalcone A (3), were isolated from licorice of Xinjiang origin (botanically assigned to Glycyrrhiza inflata Batalin), together with seven known phenolic compounds. The structure was elucidated on the basis of spectrometric evidence.