HETEROCYCLES

■ Contents

■ Tetrazole-Fragmentation for the Generation of Alkylidene Carbenes from Cyanophosphates under Neutral Conditions and Its Application to Organic Synthesis

Hiroki Yoneyama and Shinya Harusawa*

*Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

The generation of alkylidene carbenes through tetrazole-fragmentation from cyanophosphates (CPs) under neutral conditions and its application to organic synthesis are reviewed. The following topics are covered: 1) The formation of α-azidotetrazoles and their transformation into alkynes under microwave heating conditions, 2) the transformation of carbonyl compounds into homologous alkynes via CPs, 3) the synthesis of five-membered unsaturated cyclic compounds from ketones via CPs, 4) the synthesis of C4-linked Cn-triazole ribonucleoside phosphoramidites from β-ribofuranosyl-Cn-acetylenes, and 5) the synthesis of (_)-neplanocin A and one of its important synthetic intermediates using cyclopentene-formation from CPs.

■ Regiospecific Synthesis of 1-(3,4-Dihydro-2H-benzo[b][1,4]oxazin-3-yl)indolizine Derivatives Through a Three-step Sequence from 2-Arylindolizine

Min Zhang, Xinwei He, Shanqing Li, and Yongjia Shang*

*College of Chemistry and Materials Science, Anhui Normal University, 189 Jiuhua Nan Road, Wuhu, Anhui, 241000, China

Abstract

A three-step sequence for the synthesis of new indolizine derivatives containing 1,4-benzoxazine subunits is presented. Two formyl groups were firstly introduced into 2-arylindolizine via Vilsmeier-Haack reaction. Subsequent aldimine condensation gave regiospecific indolizin-1-imine product, which underwent DMAP-catalyzed cascade reaction with α-bromoketones, giving 1-(3,4-dihydro-2H-benzo[b][1,4]oxazin-3-yl)indolizine derivatives in moderate to good yields. A wide range of substrates were tolerated in this reaction. The mechanism for DMAP-catalyzed process was briefly discussed with a tentative catalytic cycle proposed.

■ Reversible Formation of an Inter-Molecular Compound Comprising 3ʹ-Aminofluorene-9-spiro-5ʹ-imidazolidine-2ʹ,4ʹ-dithione and Benzene

Yorimasa Takazawa, Tatsuo Yamamoto, Mitsuaki Suzuki, and Tomomi Sakata*

*Department of Chemistry, Faculty of Science, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

We herein describe the synthesis of 3ʹ-aminofluorene-9-spiro-5ʹ-imidazolidine-2ʹ,4ʹ-dithione through the reaction of fluorene-9-spiro-4ʹ-thiazolidine-2ʹ,5ʹ-dithione with hydrazine, and subsequent investigation of the interactions of the synthesized spirocycle-containing imidazolidinedithione with organic solvents. Recrystallization from a solvent containing benzene led to the formation of an inter-molecular compound consisting of 3ʹ-aminofluorene-9-spiro-5ʹ-imidazolidine-2ʹ,4ʹ-dithione and benzene in a 2:1 ratio through both intramolecular N-H∙∙∙S hydrogen bonds and additional weak N-H∙∙∙π interactions. The trapped benzene molecule was reversibly released by dissolution of the inter-molecular compound in acetone and subsequent concentration under reduced pressure at room temperature, and also by heating at 130–150 °C.

■ Brevisulcenal-G, -H, and -I, Polycyclic Ether Marine Toxins from the Dinoflagellate Karenia brevisulcata

Masayuki Satake,* Raku Irie, Yuka Hamamoto, Kazuo Tachibana, Patrick T. Holland, D. Tim Harwood, Feng Shi, Veronica Beuzenberg, Yoshiyuki Itoh, Fumiaki Hayashi, and Huiping Zhang

*Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

Members of two classes of marine polycyclic ether compounds, brevisulcenals (KBTs) and brevisulcatic acids (BSXs), were isolated as causative toxins from a red tide (Karenia brevisulcata) bloom event in New Zealand in 1998. The new analogues, brevisulcenals (KBTs)-G, -H, and -I, were isolated from neutral lipophilic extracts of bulk dinoflagellate culture extracts, and the molecular structures of these compounds were elucidated by detailed analyses of NMR and matrix-assisted laser desorption/ionization tandem mass spectrometry spectra, and by comparison with the spectra of KBT-F. All the analogues have the same size and arrangement of 24 ether rings, but differ in their backbone substitution patterns and degree of terminal oxidation. The cytotoxicity of these new KBT analogues was greater than that of the co-isolated, KBT-F.

■ Facile and Solvent-Free Synthesis of Quinazolin-4(3H)-ones under Microwave Condition Promoted by SbCl3

Jun Li, Weili Wang,* Xinglin Su, Xiaoling Zhang, Yan Zhang, Xuewen Zhang, Mengmeng Cai, Yuqian Cao, Juan Jin, and Yanbin Xu*

*School of chemistry and material science, Ludong University, No. 186 Hongqi Middle Road, Zhifu District, 264025, China

Abstract

Antimony trichloride (SbCl3) was found to be an effective catalyst (1 mol%) for one-pot synthesis of quinazolin-4(3H)-ones in good to excellent yields using anthranilamide and acyl chlorides under microwave irradiation. This method has the advantages of simplicity, mild reaction conditions, highly tolerant to several functional groups, as well as the avoidance of hazardous solvents.

■ Synthesis of Imidazolium Salts Bearing Two Cyclodextrins

Susumu Tsuda,* Yohei Minami, Ryoji Ueda, Takanori Iwasaki, Shin-ichi Fujiwara, Hitoshi Kuniyasu, and Nobuaki Kambe*

*Depertment of Chemistry, Faculty of Dentistry, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan

Abstract

Cyclodextrin (CD) homo and hetero dimers including an imidazolium salt were prepared from imidazolyl CDs and the corresponding CD monotosylates. The CD dimer imidazolium salts were characterized by MALDI-TOF mass and NMR spectroscopies.

■ Three New Chromone Derivatives from Cassia pumila and Their Anti-Tobacco Mosaic Virus Activity

Guang-Hui Kong, Yu-Ping Wu, Yin-Ke Li, Jing Li, Wei-Song Kong, Xin Liu, Yong Xu, Guang-Yu Yang, Qiu-Fen Hu,* and Wan-Li Zeng*

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650031, China

Abstract

Three new (1-3), together with four known chromone derivatives (4-7), were isolated from Cassia pumila. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1-3 were evaluated for their anti-tobacco mosaic virus (Anti-TMV) activity. The results showed that compounds 1-3 showed potential anti-TMV activities with inhibition rates of 28.3%, 31.2%, and 34.8%, at the concentration of 20 µM, respectively. These rates are close to that of positive control.

■ Multigram-Scale and Column Chromatography-Free Synthesis of L-Azetidine-2-carboxylic Acid for the Synthesis of Nicotianamine and Its Derivatives

Tomohiro Takaishi, Kyosuke Wakisaka, Christopher J Vavricka, Hiromasa Kiyota, and Minoru Izumi*

*Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan

Abstract

Multigram-scale synthesis of L-azetidine-2-carboxylic acid from L-aspartic acid was achieved in 13 conventional synthetic steps, without the need for purification by silica-gel column chromatography and expensive reagents. Nicotianamine and its fluorescence-labeled derivatives could be obtained from this synthetic strategy.

■ Three New Limonoids from the Fruits of Melia toosendan

Qiong Zhang,* Min Li, Qing-Hong Zheng, and Zhi-Da Min

*Department of Pharmaceutical Science, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi Province 030001, China

Abstract

Three new limonoids, 12-ethoxynimbolinins I-K (1-3) were isolated from the fruits of Melia toosendan. Their structures were established on the basis of spectroscopic methods. In addition, Compounds 1-3 were evaluated for their antibacterial activities.

■ Synthesis of 4-Amino-6-aryl-6H-pyrrolo[1,2-a][1]benzazepine-5-carbonitriles from 1-(2-Bromophenyl)-1H-pyrroles and Arylidenemalononitriles

Kazuhiro Kobayashi,* Akane Nakajima, Takashi Nogi, and Takuma Ueyama

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

Abstract

A convenient method for the preparation of 4-amino-6-aryl-6H-pyrrolo[1,2-a][1]benzazepine-5-carbonitriles has been developed. The method is based on the hydrogen bromide-mediated cyclization reaction of 2-{aryl[2-(1H-pyrrol-1-yl)phenyl]methyl}propanedinitriles, produced by the treatment of 2-(1H-pyrrol-1-yl)phenyllithiums with arylidenemalononitriles. The lithium compounds can be easily generated by the bromine/lithium exchange between 1-(2-bromophenyl)-1H-pyrroles and butyllithium.