HETEROCYCLES

■ Contents

■ Contents

■ Heterocycles Award

HETEROCYCLES Contents*

*The Japan Institute of Heterocyclic Chemistry, 1-7-17, Motoakasaka, Minato-ku, Tokyo 107-0051, Japan

■ Recent Advances in Transition-Metal-Catalyzed Synthesis of 3- and/or 4-Aryl-2(1H)-Quinolones

Yoshihiko Yamamoto*

*Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan

Abstract

2(1H)-Quinolone is a privileged nitrogen heterocycle that is found in various bioactive compounds and functional molecules. In particular, derivatives possessing aryl substituents at the 3- and/or 4-positions are significant synthetic targets as they are promising drug leads. This review surveys the synthetic methods for 3- and/or 4-aryl-2(1H)-quinolones that involve transition-metal-catalyzed construction of the 2(1H)-quinolone framework. Transition-metal-catalyzed arylations of 2(1H)-quinolone scaffolds are also surveyed.

■ Interaction of the Dihydropyridine/Pyridinium Redox Pair Fixed into a V-Shaped Conformation

Yasukazu Hirao,* Mitsuru Teraoka, and Takashi Kubo*

*Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan

Abstract

A new V-shaped molecule incorporating a dihydropyridine and a pyridinium moiety was synthesized and evaluated for its effect on the interaction between the hydride donor-acceptor pair. Spectroscopic, electrochemical, and computational studies have revealed the presence of the charge transfer interaction as a consequence of the electron donor-acceptor association.

■ Unexpected Formation of 4,7-Dihalobenzo[B]Thiophenes Using Ohira-Bestmann Reagent and Reactivity of The Halogen-Substituted Benzo[B]Thiophenes in Suzuki-Miyaura Coupling with Phenylboronic Acid

Kozo Toyota,* Hirotaka Mutoh, Hiroki Kishi, Shinichi Mikami, Hiroki Tanaka, Shuhei Yoshida, and Daisuke Naganuma

*Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan

Abstract

Reaction of 2-(1-adamantylsulfanyl)-3,6-dihalobenzaldehydes with Ohira-Bestmann reagent gave 4,7-dihalobenzo[b]thiophenes along with normal alkyne products. Nine types of 4,7-dihalobenzo[b]thiophenes bearing chlorine, bromine, or iodine atoms, were prepared by this method. Regioselectivity in Suzuki-Miyaura cross coupling reactions of the 4,7-dihalobenzo[b]thiophenes with PhB(OH)2 was also studied.

■ The One-Pot Synthesis of Pyridine Derivatives from The Corresponding 1,5-Dicarbonyl Compounds

Hiromichi Mihara, Takeru Miyakoshi, Yui Kikuchi, and Hiroyuki Konno*

*Graduate School of Science and Engineering, Yamagata University, 3-16 Jonan 4-Chome, Yonezawa 992-8510, Japan

Abstract

The optimization of the one-pot, acid-promoted synthesis of pyridine and alkylpyridine derivatives from simple alkyl-1,5-dicarbonyl derivatives and via the corresponding oxime intermediate is described. Of all the combinations of acids and solvents tested, the use of HCl in refluxing dioxane was found to result in the highest chemical yields. Twelve pyridines were prepared using this method.

■ Rearrangement Reaction in 1-Hydroxyindole Chemistry: A Synthesis of Novel 7-Substituted Yohimbine, and 4a-Substituted 1,2,3,4-Tetrahydro-β-Carboline DerivaTives1

Katsumasa Yoshino, Fumio Yamada, Koichi Noguchi, Kiyoka Kusuno, and Masanori Somei*

*Noto Marine Laboratory, Institute of Nature and Environmental Technology, Faculty of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, 56-7 Matsuhidai, Matsudo-shi, Chiba 270-2214, Japan

Abstract

X-Ray analyses of 1-hydroxyyohimbine derivatives definitely show the deviation of the N(1)—O bond from the indole molecular plane. This fact supports our working hypothesis “bishomoallylic conjugation”. The deviation is responsible for the rearrangement reaction in 1-hydroxyindole chemistry. Effective synthetic method for novel 7α- and 7β-heteroarylyohimbine, and 4aα- and 4aβ-heteroaryl-1,2,3,4-tetrahydro-β-carboline derivatives are reported.

■ Fast, Solvent-Free, and Highly Efficient Synthesis of Pyrazolo[3,4-b]Pyridines Using Microwave Irradiation and Khso4 as A Reusable Green Catalyst

Jinjing Qin, Zhenhua Li,* Xiaomeng Sun, Yi Jin, and Weike Su

*Collaborative Innovation Centre of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, 18#, Chaowang Rd., Hangzhou, Zhejiang 310014, China

Abstract

A simple, ecofriendly, and effective method was described for forming pyrazolo[3,4-b]pyridines from 5-aminopyrazoles and 3-formylchromones, in good to excellent yields, under microwave irradiation in solvent-free conditions using KHSO4 as a reusable catalyst. Some noteworthy features of this method were its cleanliness, short reaction time, easy work-up, and broad substrate tolerance. The catalyst was reused several times without losing activity.

■ Elucidation of The Conformational Properties of 3-Pyridinoyl Indoles as Intermediates of Cannabimimetics

Hideyo Takahashi,* Koji Araki, Hidetsugu Tabata, Kosho Makino, Ryohei Ujiie, Kohei Sezaki, Hiroshi Nakayama, Tetsuta Oshitari, and Hideaki Natsugari

*Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan

Abstract

The conformations of 3-pyridinoyl indoles, which are intermediates of 5-fluoropentyl-3-pyridinoyl indole, were investigated using their X-ray crystal structures. All derivatives existed as s-trans conformers. A pseudo-planar conformation was observed in the 2'-yl isomer of 3-pyridinoyl indoles. On the other hand, twisted conformations were observed in 3-pyridinoyl 2-methylindoles. The conformations of these compounds in solution were also investigated using VT-NMR.

■ Anti-Tmv Isoquinoline Alkaloids from The Whole Plants of Thalictrum glandulosissimum

Chun-Man Song,* Guang-Hui Kong, Yu-Ping Wu, Eric Yin, Bradley Liu, Zhen-Yuan Xia, Hai-Tao Huang, Guang-Yu Yang, and Qiu-Fen Hu*

*Chemistry, Cyats, Keyi Rd 653100, China

Abstract

Three new (1-3), together with three known (4-6) isoquinoline alkaloids were isolated from the whole plants of Thalictrum glandulosissimum. Their structures were elucidated by spectroscopic methods, including extensive 1H, 13C, and 2D-NMR techniques. Compounds 1-6 were evaluated for their anti-tobacco mosaic virus (Anti-TMV) activity. The results revealed that compounds 2, 3 and 4 showed potential anti-TMV activities with inhibition rates of (35.6±3.5)%, (36.2%±3.8)%, (46.3%±3.2)%, at the concentration of 20 µM, respectively. These rates are higher than that of positive control.

■ A Propeller-Shaped Mesomeric Betaine, Tetraphenylbenzene-1-Quinolinium-2-Benzoate

Sviatoslav Batsyts, Felix Lederle, Eike G. Hübner, Jörg Adams, Jan C. Namyslo, and Andreas Schmidt*

*Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany

Abstract

4-[(Quinolin-4-yl)ethynyl]benzoic acid underwent a cycloreaction with tetraphenylcyclopentadienone to give the hexa(hetero)arylbenzene- 1-(quinolin-4-yl)-2-(4-benzoic acid)-3,4,5,6-tetraphenylbenzene which was N-methylated and finally deprotonated to give the title compound. The molecule adopts a propeller-shaped configuration in which the benzoate ring as well as the phenyl ring adjacent to the quinolinium substituent display non-isochronous resonance frequencies, respectively, due to a hindered rotation. Although the molecule formally belongs to the class of pseudo-cross-conjugated heterocyclic mesomeric betaines, the propeller-shape causes a charge distribution of cross-conjugated systems. DFT-calculations (frontier orbital profiles, geometries) have been carried out.