HETEROCYCLES

■ Contents

■ Asymmetric Construction of Heterocycles via Dearomative Coupling and Addition Reactions of Phenol and Aniline Derivatives

Kotaro Kikushima,* Hideyasu China, and Toshifumi Dohi*

*College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

Abstract

Efficient methods for the formation of chiral heterocycles are considerably important in the synthesis of naturally-occurring compounds and pharmaceutical products. This review highlights the formation of chiral heterocycles through dearomative bond-formations as the key reactions, wherein the phenol or aniline derivatives serve as the nucleophiles. Transition-metal-catalyzed intramolecular coupling reactions in the presence of chiral ligands afford the enantioenriched multicyclic compounds bearing heterocycles. Chiral bifunctional organocatalysts induce the formation of dearomative coupling products, which could be converted to heterocycles through further transformations.

■ A Highly Selective Fluorescence-Enhanced Probe for the Rapid Detection of SO2 Derivatives and Its Bio-Imaging in Living Cells

Yaogen Zhou, Yiwei Zhou, Hongying Wang,* and Baoquan Chen*

*School of Chemistry and Chemical Engineering, Tianjin University of Technology, 391 Binshui Xidao, Xiqing District Tianjin 300384, China

Abstract

In this study, we report a simple coumarin-based probe CISD for the detection of SO2 derivatives. In the case of the probe CISD, HSO3− can induce an obvious fluorescence-enhanced response with high selectivity, fast response (within 10 sec) as well as low limit of detection (262 nM). HR-MS experiment revealed the sensing mechanism concerning the nucleophilic addition reaction. Furthermore, the probe CISD has been successfully applied for imaging exogenous HSO3− in living HeLa cells.

■ Piperidine and Azetidine Formation by Direct Cyclization of Diols with N-Nonsubstituted Sulfonamide under the Mitsunobu Conditions Utilizing (Cyanomethylene)tributylphosphorane (CMBP) and Its Application to the Synthesis of Lupinine

Hiroto Kaku,* Yuhei Sonoda, Hideyuki Hishida, Yuri Taniguchi, Akiko Kubo, Takumi Hamaguchi, Mitsuyo Horikawa, Makoto Inai, Kei Kitamura, and Tetsuto Tsunoda*

*Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-machi, Tokushima, 770-8514, Japan

Abstract

(Cyanomethylene)tributylphosphorane (CMBP) can promote the Mitsunobu reaction of 1,3- and 1,5-diols with N-nonsubstituted sulfonamides, such as tosylamide (TsNH2) and 3,3-dimethoxypropylsulfonamide (DimpsNH2), to prepare azetidine and piperidine ring systems directly. Utilizing this methodology, lupinine, a biologically active piperidine alkaloid, was synthesized.

■ Sugar Based γ-Amino Alcohol Organocatalyst for Asymmetric Michael Addition of β-Keto Esters with Nitroolefins

Divakar Ganesan, Madhu Chennapuram, Zubeda Begum, Chigusa Seki, Yuko Okuyama, Eunsang Kwon, Koji Uwai, Michio Tokiwa, Suguru Tokiwa, Mitsuhiro Takeshita, and Hiroto Nakano*

*Division of Sustainable and Environmental Engineering, Graduate School of Engineering, Muroran Institute of Technology, 27-1 Mizumoto, Muroran, Hokkaido 050-8585, Japan

Abstract

Sugar based γ-amino alcohol was used in asymmetric Michael addition of β-keto esters with nitroolefins for the first time affording the corresponding several chiral Michael adducts bearing quaternary chiral carbon center in moderate to good chemical yields and stereoselectivities (up to 98%, up to dr. 95:5, up to 84% ee).

■ One-Pot Synthesis of 3-(Guaiazulen-3-yl)dihydro-1H- indol-4(5H)-ones via Domino Reaction

Lu Zhang, Dao-Lin Wang,* Jin-Juan Xing, and Lin Liu

*College of Chemistry and Chemical Engineering, Bohai University, 19, Keji Rd., New Songshan District, Jinzhou City, Liaoning Province 121001, China

Abstract

A facile and efficient one-pot procedure for the preparation of 3-(guaiazulen-1-yl)dihydro-1H-indol-4(5H)-ones by a catalyst-free, three- component reaction of guaiazulene, methylglyoxal and enaminones under mild conditions in good yield is reported.

■ Facile Synthesis of (Guaiazulen-1-yl)-1H-pyrroles via Paal-Knorr Reaction

Lu Zhang, Dao-Lin Wang,* Jin-Juan Xing, and Lin Liu

*College of Chemistry and Chemical Engineering, Bohai University, 19, Keji Rd., New Songshan District, Jinzhou City, Liaoning Province 121001, China

Abstract

An efficient and simple method for the synthesis of (guaiazulen-1-yl)-1H-pyrroles was described. The construction of this new heteroarylazulene system was achieved by a the Paal-Knorr reaction of 3-acetyl-4-(guaiazulen-1-yl)hexane- 2,5-dione (4), easily preparation by a three-component condensation of guaiazulene (1), methylglyoxal (2) and acetylacetone (3), with primary amines (5).

■ One-Pot Synthesis of Pyrrolo[2,1-α]isoquinolines via Tandem Reactions of Vinylselenonium Salt, 2-Bromoethanones, and Isoquinoline

Qi Sun, Minghong Liao, Yan Zhao, Yunxia Li, Shanshan Liu, Deshou Mao,* and E Tang*

*School of Chemical Science and Technology, Yunnan University, No. 2 Green Lake North Road, Kunming 650091, China

Abstract

An convenient and one-pot synthesis of pyrrolo[2,1-a]isoquinolines via the tandem reaction of methyl(phenyl)vinylselenonium salt with isoquinoline and 2-bromoethanones has been developed, which features very mild conditions, available substrates, simple experimental procedures, moderate to good yields, and wide functional group tolerance.

■ Isochromophilol A, a New Azaphilone Isolated from Penicillium sp. RO369, a Leaf Litter Inhabiting Fungus from Tsuga diversifolia

Kan'ichiro Ishiuchi,* Dai Hirose, Yoriko Takahashi, Ryu Miyagawa, Kohei Watanabe, and Susumu Kitanaka*

*Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-Dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan

Abstract

A new sclerotiorin-type azaphilone, isochromophilol A (1), was isolated from Penicillium sp. RO369 associated with Tsuga diversifolia, along with eight known compounds (2−9). The structure of 1 was elucidated on the basis of spectroscopic data. Isochromophilol A (1) (16 μg) showed weak anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity with an inhibition diameter of 8.8 ± 1.0 mm

■ Some Hybrid Linker Mode C2-Symmetrical 1,3,5-Triazine Derivatives and Their Biological Evaluation

Nobuko Mibu, Makoto Furutachi, Yusuke Inoue, Yuka Fujita, Yumemi Matsumoto, Yuki Kawano, Syoko Tomonaga, Junko Matsuyama, Kanae Yamada, Ryo Sato, Kazumi Yokomizo, Jian-Rong Zhou, Shunsuke Shimomura, Kaori Ota, and Kunihiro Sumoto*

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

We report the preparation of some new C2-symmetrical multivalent hybrid-type molecules having a methylene linker group and 1,3,5-triazine (TAZ) recognition moieties in the molecule and we also report the results of biological evaluation of their anti-herpes simplex virus type 1 (anti-HSV-1) activity and cytotoxic activity against Vero cells. All mid-size C2-symmetrical multivalent hybrid-type molecules (3a-2, 3a-4, 3b-2, 3b-3, 3b-4) showed considerably high levels of anti-HSV-1 activity (EC50 = 7.6 ~ 95.6 μM) with low levels of cytotoxicity (CC50 > 200 μM) against Vero cells. Among the tested compounds, the hybrid-type C2-symmetrical multivalent molecule (3a-4) seems to be an interesting new lead in the search for new hybrid-type multivalent mid-size antiviral compounds.