HETEROCYCLES

■ Contents

■ Construction of Unique Heterocyclic Frameworks by Photochemical Reaction of 5- and 6-Membered Heteroaromatics

Noriyoshi Arai* and Takeshi Ohkuma*

*Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628, Japan

Abstract

Photochemical reaction is an attractive synthetic method since it enables peculiar transformations that are not achievable under thermochemical reaction conditions. Construction of heterocyclic frameworks is one of the largest research fields in synthetic organic chemistry, but the utilization of photochemical reactions for heterocyclic-framework construction is limited to such reactions as typical [2+2] cycloaddition reaction, dye-sensitized generation of singlet oxygen, and photochemical radical generation. In this review, we focus on novel methods for the construction of unique molecular frameworks by means of photochemical reactions of heteroaromatic cyclic compounds, including mainly 5-membered heteroaromatics, furans, thiophenes, thiazoles, and oxazoles, as well as several 6-membered compounds. In some cases, heteroaromatic compounds act as acceptors of other photochemically excited molecules, such as 3(n-π*) of carbonyl compounds, and in other cases the heteroaromatic compounds themselves are excited to generate reactive species that participate in the unique bond-forming reactions.

■ Synthesis and Antifungal Activities of Pyridine Bioisosteres of a Bismuth Heterocycle Derived from Diphenyl Sulfone

A. F. M. Hafizur Rahman, Toshihiro Murafuji,* Kazuki Yamashita, Masahiro Narita, Isamu Miyakawa, Yuji Mikata, Katsuya Ishiguro, and Shin Kamijo

*Graduate School of Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan

Abstract

Heterocyclic iodobismuthanes 7–9 [IBi(C6H4-2-SO2C5H3N-1´-)] derived from phenyl pyridinyl sulfones were synthesized. Their antifungal activities against the yeast Saccharomyces cerevisiae were compared with those of halobismuthanes [XBi(RC6H3-2-SO2C6H4-1´-)] (1: X=Cl; 2: X=I, R=H) derived from diphenyl sulfone derivatives to determine how the bioisosteric replacement of the benzene ring in 2 with the pyridine ring in 7–9 affects their activities. The antifungal activities of 7–9 were higher or comparable to those of 1 and 2. The DFT calculations suggested that the generation of the antifungal activity of the bismuthanes was well understood by the nucleophilic addition of methanethiolate anion as a model biomolecule at the bismuth atom to give an intermediate ate complex.

■ Four Cyclodipeptides, Asnovolenins A-B and Asnovozines A-B, from Aspergillus novofumigatus

Kazuki Ishikawa, Daigo Wakana, Takeshi Itabashi, Hisashi Takeda, Takashi Yaguchi, Ken-ichi Kawai, and Tomoo Hosoe*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Four new cyclodipeptides, asnovolenins A (1) and B (2), and asnovozines A (3) and B (4), were isolated from the fungus Aspergillus novofumigatus CBS 117520. The structures of 1-4 were determined by the detailed analysis of mainly 1D- and 2D-NMR and MS data. Compounds 1 and 2 are composed of epi-aszonalenin (5) and dihydroterrein (6), and they are 2’-epimers of each other. Compounds 3 and 4 consist of D-alanine and tryptophan attached to a 3-methyl-1-butene group. The stereochemistry of 1 and 2 was determined from ROESY spectra and the exciton chirality method from CD spectra, and that of 3 and 4 was determined from NOE or NOESY spectra using the modified Marfey’s method.

■ A Practical Synthesis of 2-Substituted 5-Bromoindoles

Yang He, Lianlian Fan, Haoting Zhu, Xiaolin Li, Pu Zhou, and Yu Luo*

*Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China

Abstract

This paper describes a non-cryogenic synthetic procedure for a variety of 2-substituted 5-bromoindoles. The direct magnesiation of 5- bromo-1-(4-toluenesulfonyl)indole with a mixture of i-PrMgCl/LiCl and diisopropylamine allows for the preparation of various 2-substituted indoles. The advantages of this procedure include the non-cryogenic conditions, simple operations and inexpensive Grignard reagents. In addition, this procedure is especially advantageous for the preparation of 2,5-dibromoindole with reduced synthetic steps, low production cost and good overall yields.

■ Novel Antioxidant Isolated from Warcupiella spinulosa JCM 2358, 7-Hydroxycordylactam

Ryosuke Shigemoto, Ken-Ichi Oinuma, Shunsuke Masuo, and Naoki Takaya*

*Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan

Abstract

We identified a new compound, 7-hydroxycordylactam, together with the known compound, cordylactam, from cultured Warcupiella spinulosa JCM 2358. Their structures were elucidated using high-resolution mass spectrometry and NMR spectroscopy. The spectra indicated that these compounds have a γ-lactam-fused γ-pyrone skeleton. Analysis of their antioxidant activities showed that both 7-hydroxycordylactam and cordylactam scavenged 1,1-diphenyl-2-picrylhydrazyl radicals with an IC50 of 340 µM.

■ One-Pot Synthesis of Model 1H,1'H-5,5'-Bi(1,2,4-Triazoles)

Mustafa M. El-Abadelah, Monther S. Zreid, and Mohammed M. Abadleh*

*Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, University of Petra, Amman 11196, Jordan

Abstract

Direct interaction of diaminomaleonitrile with model in situ generated nitrile imine 1,3-dipoles resulted in a direct synthesis of the corresponding 5,5'-bi(1,2,4-triazoles). A plausible mechanism is advanced for this new preparative route.

■ Preparation of Novel Bivalent Linker Mode Phenylboronic Acid Derivatives and Their Biological Evaluation

Makoto Furutachi, Ayaka Matsumoto, Tetsuya Tamenaga, Aya Sugita, Misato Kuroiwa, Kazumi Yokomizo, Jian-Rong Zhou, Nobuhiro Kashige, Fumio Miake, and Kunihiro Sumoto*

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

Abstract

We report a new route to the preparation of C2-symmetrical bivalent phenylboronic acids having alkyl linker groups in the molecule and results of biological evaluation of their biological activity and cytotoxic activity against Vero cells. Among the tested compounds, C2-symmetrical bivalent meta-oriented phenylboronic acid 2f (n=7) showed high cytotoxic activity (CC50=5.43 μM) against Vero cells. The results of an SAR study suggested that the presence of a C7-methylene linker group in the molecule is an important structural factor for expression of potential cytotoxic activities. A sugar recognition property of this C2-symmetrical geometric molecule was suggested by NMR analysis of compound 2f with methyl α-D-glucopyranoside 6.

■ Pyrimidine Derivatives of N-Acetylguanidine: Novel Inhibitors of Sodium-Hydrogen Exchanger 1

Alexander Ozerov,* Mikhail Novikov, Alexander Spasov, Igor Iezhitsa, Natalia Gurova, and Valeria Gurova

*Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq. 1, Volgograd 400131, Russia

Abstract

Sodium-hydrogen exchanger (Na+/H+) type 1 (NHE-1) inhibitors have been shown to protect the heart during ischaemia and early reperfusion. As such, NHE-1 inhibitors are of special interest for clinical development for the attenuation of both acute and chronic post-myocardial infarction responses. New pyrimidine derivatives of N-acetylguanidine containing fragments of uracil, thymine, and their 3-benzyl derivatives were synthesised. These compounds showed in vitro inhibitory effects on NHE-1 that were significantly higher than those of zoniporide in platelet swelling assays.

■ Cs2CO3 Promoted [3+4] Annulation of Sulfur Ylides and Alkenylthiazolones: Synthesis of 5,8-Dihydrooxepino[2,3-d]thiazole Derivatives

Yin He, Aimin Yu, and Xiangtai Meng*

*Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China

Abstract

An efficient [3+4] annulation reaction of crotonate-derived sulfur ylides and alkenylthiazolones is described. Crotonate-derived sulfur ylides act as a three-carbon synthon in this [3+4] annulation reaction, which was rarely reported before. This new methodology is particularly effective for the synthesis of 5,8-dihydrooxepino[2,3-d]thiazole derivatives.

■ Cinchona Alkaloid Thiourea Catalyzed Asymmetric Synthesis and Anticancer Activity Evaluation of Tetrahydro-β-spirooxindoles

Liang Qi, Huacui Hou, Fei Ling, Lu Fang, Wenjun Luo, and Weihui Zhong*

*Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, No.18 Chaowang Road, 6th Zhaohui District, Hangzhou, Zhejiang Province 310014, China

Abstract

Asymmetric synthesis and activity evaluation of tetrahydro-β-spirooxindole compounds is reported in this paper. Cinchona alkaloid thiourea has been utilized as catalyst for the asymmetric synthesis of tetrahydro-β-spirooxindoles, affording the desired products in moderate to good yields and with up to 94:6 er. Interestingly, the spirooxindoles exhibited moderate to good in vitro antitumor activity for A549 cells. Besides, the growth inhibitory activities of these selected compounds against normal lung cell CHL cells were further evaluated.

■ Errata “Synthesis of Novel Angular and Linear Fused [5-6-5] Heterocycles by the Reaction of Methyl Cyano-(3-cyano-4,5-dihydro-2(3H)-furanylidene)acetate with Hydrazines and Dimethylformamide Dimethyl Acetal”: HETEROCYCLES, 2018, 96, 664, DOI: 10.3987/COM-17-13861

Fumi Okabe-Nakahara,* Eiichi Masumoto, Hiroshi Maruoka, and Kenji Yamagata

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