HETEROCYCLES

■ Contents

■ SYNTHESIS OF 3,7,9- AND 2,6,9-TRIAZABICYCLO[3.3.1]NONANE DERIVATIVES

Ambara R. Pradipta and Katsunori Tanaka*

*Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan

Abstract

Due to their interesting chemical and biological properties, nitrogen containing-heterocycles represent indispensable moiety in organic chemistry. From the various types of nitrogen containing-heterocycles, azabicyclic compounds in particular are of considerable importance in many aspects and have attracted attention from wide range of fields, including in the study of natural products, coordination properties, or in the development of biologically and pharmacologically active compounds. This review focuses on the hitherto reported methods for the synthesis of the triazabicyclo[3.3.1]nonane derivatives, the bicyclic compound having two nitrogen atoms at the eight-membered ring and one nitrogen atom at the bridge position, which are less explored in the literature probably due to difficulties in their synthetic accessibility.

■ Palladium-Catalyzed Mizoroki-Heck Type Reaction with Aryliodine Diacetates Using Hydrazone Ligand

Takashi Mino,* Kohei Watanabe, Taichi Abe, Taketo Kogure, and Masami Sakamoto

*Department of Applied Chemistry and Biotechnology, Graduate School and Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

We developed a palladium-catalyzed Mizoroki-Heck type reaction of olefins with such hypervalent iodine reagents as iodobenzene diacetate in good to high yields using 2 mol% of a heterocyclic hydrazone (1b)-Pd(OAc)2 system in NMP under air at 90 °C.

■ Facile Synthesis of Indolines by a Tandem Nitro-reduction Aza Michael Addition Reaction

Wellington Martins Ventura, Luiz Guilherme Souza de Assis, and Jason Guy Taylor*

*Department of Chemistry, Federal University of Ouro Preto, Bauxita, ICEB, UFOP, Ouro Preto 35400-000, Brazil

Abstract

A diverse array of substrates are conveniently prepared by coupling diazonium salts to ethyl vinyl ether and subjecting the resultant aldehyde intermediate to a Wittig reaction to provide α,β-unsaturated esters with only one purification step. The cyclisation of 4-aryl-but-2-enoates is carried out in the presence of stoichiometric amounts of SnCl2∙2H2O and thus this one-pot strategy also permitted the expeditious synthesis of indolines in good yield.

■ INTENTIONAL SYNTHESIS OF BINARY RADICAL THAT BEARING NITRONYL AND IMINO NITROXIDES: X-RAY ANALYSIS AND MAGNETIC MEASUREMENT

Fumiyasu Iwahori,* Takayuki Suzuki, and Kosuke Kato

*Department of Chemistry, College of Humanities and Sciences, Nihon University, Sakurajousui, Setagaya-Ku, Tokyo 156-8550, Japan

Abstract

We have synthesized new binary radical that bearing both nitronyl and imino nitroxides with the aim of enabling to control the occupancy of oxygen atom in the nitronyl nitroxide crystal. X-ray analysis, ESR study and magnetic measurement revealed that the tuning of occupancy of the oxygen atom in the crystal might make an effect on the magnetic property of nitronyl nitroxides.

■ GYMNOCIN-A CARBOXYLIC ACID AND GYMNOCIN-A2, CYTOTOXIC POLYETHERS FROM THE RED TIDE DINOFLAGELLATE KARENIA MIKIMOTOI

Yoshihisa Tanaka, Masayuki Satake,* Mari Yotsu-Yamashita, and Yasukatsu Oshima

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

Abstract

Gymnocins are a series of cytotoxic polyether compounds isolated from the notorious red tide dinoflagellate Kareia (formerly Gymnodinium) mikimotoi. Among them, the structures of gymnocin-A and gymnocin-B have already been elucidated. Gymnocin-A carboxylic acid and a new analog of gymnocin-A, gymnocin-A2, were isolated from K. mikimotoi cells, and their structures were determined by detailed analysis of 2D-NMR spectra. The structural changes of gymnocin-A carboxylic acid and gymnocin-A2 occurred on the terminal side chain and ring A in gymnocin-A. Gymnocin-A carboxylic acid and gymnocin-A2 showed moderate cytotoxicity against P388 cells.

■ Alkaloids from Melodinus suaveolens

Ting-Ting Zhang, Zhi-Wen Liu, Wen-Jing Wang, Yong-Bin Tong, Fang-Fang Xu,* Jing-Quan Yuan, Bo Liu, Xiao-Qi Zhang,* and Wen-Cai Ye

*Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China

Abstract

Two new quinoline alkaloids, 14,15-β-epoxyscandine (3) and meloscine N-oxide (6), along with six known alkaloids scandine (1), scandine N-oxide (2), meloscandonine (4), meloscine (5), tubotaiwine (7), polyneuridine (8) were isolated from the twigs and leaves of Melodinus suaveolens. The structures of the new compounds were elucidated on the basis of spectroscopic methods and circular dichroism experiments.

■ Synthesis of Chromeno[2,3-b]indole Derivates

Eszter Gráczol-Fördős, Tibor Novák, Gábor Blaskó, Imre Fejes, François Perron-Sierra, and Miklós Nyerges*

*CHL, Servier Research Institute of Medicinal Chemistry, Záhony utca 7, H-1031 Budapest, Hungary

Abstract

Several new chromeno[2,3-b]indole tetracycles were synthesized by the reaction of 2’-hydroxyacetophenones or 2’-hydroxypropiophenones and salicylaldehyde derivates. Under the harsh reaction conditions, the initially formed Knoevenagel adducts lost water, giving rise to the formation of ring closed tetracyclic products.

■ SYNTHESIS OF 4-METHOXY and 5-METHOXY SUBSTITUTED 7-AZA-ISOINDOLIN-1-ONES

Heng Zhou, Guanglong Sun, Zeng-Lu Liu, Xiao-Ping Zhan, and Zhen-Min Mao*

*School of Pharmacy, Shanghai Jiaotong University , No.800 Dongchuan Road, Minhang District, Shanghai 200240, China

Abstract

A simple and convenient route for the synthesis of a series of 4-methoxy or 5-methoxy substituted 7-aza-isoindolin-1-ones is described. Methoxyl substituted pyridine derivatives were cyclized with different amines under alkaline condition to give the desired products.

■ EFFICIENT SYNTHESIS OF PURINE DERIVATIVES BY ONE-POT THREE-COMPONENT MANNICH TYPE REACTION

Qian Zhang,* Bai-Wei Ma, Yong-Zhen Huang, Qian-Qian Wang, Xing-Xing Wang, Gui-Rong Qu, and Hai-Ming Guo*

*School of Chemical and Chemical Engineering, Henan Normal University, 46# East of Construction Road, Xinxiang, Henan 453007, China

Abstract

An efficient, facile three-component Mannich-type reaction on purine rings was described. This reaction proceeded smoothly under the catalysis of ethylenediamine at ambient temperature in high regioselectivities with exclusive N9-alkylated products. A wide range of purine derivatives were obtained in high yields.

■ A MICROWAVE ASSISTED SYNTHESIS OF HIGHLY SUBSTITUTED 7-METHYL-5H-THIAZOLO[3,2-a]PYRIMIDINE-6-CARBOXYLATE DERIVATIVES VIA ONE-POT REACTION OF AMINOTHIAZOLE, ALDEHYDE AND ETHYL ACETOACETATE

Bing Zhao, Li-Li Jiang, Zhuo Liu, Qi-Gang Deng,* Li-Yan Wang, Bo Song, and Yan Gao*

*College of Chemistry and Chemical Engineering, Qiqihar University, 42 Wenhuadajie, Qiqihar, Heilongjian Shang, 161006, China

Abstract

The synthesis of highly substituted 7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives by one-pot reaction of aminothiazole, aldehyde and ethyl acetoacetate under microwave irradiation have been accomplished without any catalyst. This approach provides a simple, rapid, and green method for the synthesis of 7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives.

■ Xanthone Derivatives form the Fermentation Products of an Endophytic Fungus of Phomopsis amygdali

Qiufen Hu, Deyun Niu, Shuai Yang, Hongyun Cao, Chunyang Meng, Haiyin Yang, Xuemei Gao,* and Gang Du*

*Key Laboratory of Ethnic Medicine Resource Chemistry, State Ethnic Affairs Commission & Ministry of Education, School of Chemistry and Biotechnology, Yunnan University of Nationalities, Kunming, Jingming South Road, Chenggong New District, Kunming, Yunnan 650500, China

Abstract

Two new xanthones, 1,5-dihydroxy-3-(2-oxopropyl)-6-methoxycarbonylxanthone (1) and 1-hydroxy-3-(2-oxopropyl)-8-methoxycarbonyl- xanthone (2), together with four known xanthones (3-6) were isolated from the fermentation products of a Phomopsis fungus. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compound 1 showed high cytotoxicity against A549 and PC3 cell with IC50 values of 3.5 and 2.8 μM. Compound 2 showed high cytotoxicity against PC3 cell with IC50 value of 2.4 μM. The other compounds also showed moderate cytotoxicity for some tested cell lines with IC50 values between 5.2-8.6 μM.

■ C–H MODIFICATION OF 2-AZAADAMANTANE: SYNTHESIS OF C5-FUNCTIONALIZED AZADOS FOR ADVANCED USE

Yusuke Sasano, Tomohiro Nishiyama, Masaki Tomizawa, Masatoshi Shibuya, and Yoshiharu Iwabuchi*

*Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aobayama, Sendai 980-8578, Japan

Abstract

Regioselective C–H functionalization of N-protected 2-azaadamantane was achieved via a radical-induced bromination. The obtained 5-bromo-2-azaadamantane is readily transformed to arylated/alkylated 2-azaadamantane N-oxyls [AZADOs], which exhibit high catalytic activities for alcohol oxidation.

■ Simple and Stereocontrolled Preparation of Benzoylated Phenylalanine Using Friedel–Crafts Reaction in Trifluoromethanesulfonic Acid for Photoaffinity Labeling

Yuta Murai, Lei Wang, Yasuyuki Muto, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, and Makoto Hashimoto*

*Division of Applied Science, Graduate School of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan

Abstract

Simple and stereocontrolled preparation of benzoylated phenylalanine derivatives from optically pure phenylalanine using Friedel–Crafts reaction in trifluoromethanesulfonic acid (TfOH) is reported; these derivatives are useful for photoaffinity labeling. Protected or unprotected phenylalanine derivatives converted to benzoyl derivatives in TfOH at room temperature in a short time without loss of optical purity. The reaction condition was applied to synthesize novel photoreactive phenylalanine derivative, which has two photophores (benzophenone and diazirine). The detail analysis of photo-irradiation for two different photophores contained phenylalanine derivative was also investigated.

■ Correction to ”Recent Advances in the Syntheses of Decalin Type Natural Products”: HETEROCYCLES, 2013, 87, 1625, DOI: 10.3987/REV-13-773

Hiroyuki Akita*

*Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan