HETEROCYCLES

■ Contents

■ Heterocycles Award

HETEROCYCLES Announcement*

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

■ Nanostrucure Formation Based on the Functionalized Side Chains in Liquid-Crystalline Heteroaromatic Compounds

Atsushi Seki and Masahiro Funahashi*

*Deparment of Advanced Materials Science, Faculty of Engineering, Kagawa University, 2217-20 Hayashi-cho, Takamatsu, Kagawa 761-0396, Japan

Abstract

Heteroaromatic skeletons are important functional units for optic and electronic materials. For the construction of novel functional soft matter, the self-assembled system utilizing the heteroaromatic molecules bearing various substituents provide an effective approach. Recently, a lot of liquid crystals and fibrous aggregates with electronic functions have been developed. Among them, liquid-crystalline (LC) semiconductors are well-known examples. LC semiconductors are hopeful candidates which cope with both carrier transport property and solubility. Although the optimization of the chemical structures of the central aromatic core has been mainly considered in the past study, side chains also play a key role to form the well-defined nanosegregated superstructures. The structural optimization of the side chains as well as the rigid cores contributes to the developments of the “soft matter electronics”. Herein, we will review the recent research trend on functional π-conjugated liquid crystals focusing on the flexible side chains. Furthermore, we will describe the importance of the nanosegregation for the design of soft materials having electronic functions.

■ Applications of C-H Insertion Reaction in Total Synthesis of Biologically Active Heterocyclic Natural Products

Toshiyuki Kan,* Tomohiro Asakawa, and Makoto Inai

*Synthetic Organic ＆ Medicinal Chemistry, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka 422-8526, Japan

Abstract

Here, we summarize our work on applications of the Rh-catalyzed C-H insertion reaction to syntheses of heterocyclic natural products. Total synthesis of racemic serotobenine (4) was achieved in an optical active form. Enantioselective synthesis of SB-203207 (25) was accomplished via desymmetric C-H insertion reaction of 33 to construct the bicyclo[3.3.0] framework. Stereoselective synthesis of MFPA (53) was accomplished with the aid of an intermolecular C-H insertion reaction. Synthesis of aperidine (70) featured cis-selective construction of the dihydrobenzofuran ring of 81 by utilizing Hashimoto’s catalyst.

■ Brevisulcatic Acids from a Marine Microalgal Species Implicated in a Toxic Event in New Zealand

Raku Irie, Rina Suzuki, Kazuo Tachibana, Patrick T. Holland, D. Tim Harwood, Feng Shi, Paul McNabb, Veronica Beuzenberg, Fumiaki Hayashi, Huiping Zhang, and Masayuki Satake*

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

Abstract

Ladder-frame polyethers, known as brevisulcatic acids (BSXs) -1 (1), -2 (2), -4 (3), -5 (4) and -7 (5), were isolated from the dinoflagellate Karenia brevisulcata as potential causative toxins of a harmful algal event in New Zealand in 1998. The structures of 2, 4, and 5 were elucidated in this study. Brevisulcatic acids possessed a common fused nine ether-ring backbone, with a size and sequence determined to be 8/6/8/9/7/7/6/6/6. Rings B, C, H, I and J of the brevisulcatic acids were similar to those of brevetoxin A, a well-known polyether toxin. BSX-5 (4) had a γ-lactone as the 5-membered A-ring, analogous to brevetoxin A, while in BSX-2 (2) and BSX-7 (5) the lactone was present in its seco-acid form. In addition to this backbone variation, there were also some structural difference in side-chain substituents, with 2 and 4 having a 2-methylenepropionic acid unit, and 5 a 2-methylenepropanol unit. Cytotoxicity of 4 against neuroblastoma cells indicated that not only the structures but also activity of brevisulcatic acids are similar to those of brevetoxin A. This indicates that brevisulcatic acids potentially played a significant role in the toxicity observed during the only documented Karenia brevisulcata bloom to date.

■ Solvent Extraction Ability of New Diethyl Phosphate-Modified Thiacalix[6]arene towards PGM Solution

Kunda Uma Maheswara Rao, Takashi Kimuro, Manabu Yamada, Yoshihiko Kondo, and Fumio Hamada*

*Department of Applied Chemistry, Akita University, Tegata-gakuenncho 1-1, Akita 010-0852, Japan

Abstract

New lower rim modified phosphorylated thiacalix[6]arene derivative such as TC6A-phosphate (2) was synthesized. IR, 1H & 31P NMR and mass spectral and elemental analysis characterized the structure of the synthesized compound. We also investigated the metal extraction ability of the newly synthesized compound through solvent extraction technique from automotive catalyst residue, standard mixed metal, standard Pd and Zr solutions. This compound showed high selectivity towards Zr and Pd ions.

■ An Efficient Synthesis of 2-Selenouridine and Its Phosphoramidite Precursor

Masakazu Kogami, Darrell R. Davis, and Mamoru Koketsu*

*Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu, Gifu 501-1193, Japan

Abstract

We describe an efficient and scalable synthetic route to the natural occurring 2-selenouridine (Se2U) and its suitably protected derivative for phosphoramidite synthesis. From known fully TBDMS-protected thiouridine, the corresponding selenouridine was synthesized via the reaction of methylthiouridine with NaHSe, which was then completely deprotected without affecting the selenocarbonyl moiety to deliver Se2U. Next, Se2U was converted into the 2′-O-TBDMS-5′-O-DMT derivative in 81% yield over four steps including di-tert-butylsilylene (DTBS) introduction at O3′ and O5′, O2′-silylation, selective cleavage of DTBS, and DMT introduction. This synthetic route enabled gram-scale preparation of both Se2U and its phosphoramidite precursor in excellent yields. Furthermore, the predicted C3′-endo conformational preference of Se2U was experimentally confirmed by NMR spectroscopy.

■ Facile and Efficient Access to Tetrahydrobenzo[b]pyrans Catalyzed by N,N-Dimethylbenzylamine

Hamzeh Kiyani* and Mozhgan Sadat Jalali

*School of Chemistry, Damghan University, Cheshmeh Ali Road, Daneshgah square, Damghan 36715-364, Iran

Abstract

The N,N-dimethylbenzylamine (DMBA) has been used as an efficient, inexpensive, and commercially available organocatalyst for the one-pot, three-component synthesis of tetrahydrobenzo[b]pyrans in good to high yields. It was found that the one-pot Knoevenagel-Michael-Thorpe-Ziegler cyclization sequence of dimedone, malononitrile/ethyl cyanoacetate, and various aldehydes was efficiently implemented in ethanol at 45 °C. This procedure offers attractive several features: mild reaction conditions, use of ethanol as a green solvent, reusability the reaction media, shorter reaction times, and the ease of the work-up.

■ Radical Scavenging Activity of Ascorbic Acid Analogs Containing a Carbonyl Conjugated Ene-Diol Structure

Shogo Nomura, Keiko Inami, and Masataka Mochizuki*

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

Abstract

Small molecule antioxidants such as ascorbic acid (AscH2) prevent the oxidative damage of biological molecules by scavenging reactive oxygen species. A carbonyl-conjugated ene-diol structure is essential for the antioxidant activity of AscH2. As such, we synthesized novel AscH2 analogs containing a carbonyl conjugated ene-diol structure and evaluated their radical scavenging activities. When the 1,2-dihydroxyethyl group was removed, radical scavenging activity equal to AscH2 was observed. Analogs containing an endocyclic nitrogen atom instead of a ring oxygen displayed higher radical scavenging activities than AscH2. Therefore, the electron donating effect of the carbonyl conjugated ene-diol structure greatly increased the radical scavenging activity of AscH2 analogs.

■ TfOH-SiO2 as an Efficient and Recyclable Catalyst for Synthesis of 3-Arylbenzofurans

Baolong Wang, Jiaxing Hu, Fanglin Zhang, and Hua Zheng*

*School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, 122 Luoshi Road,Wuhan,Hubei 430070, China

Abstract

A convenient process for the synthesis of 3-arylbenzofurans and their derivatives by 2-phenoxy-1-phenylethanones via TfOH-SiO2 catalyzed is developed. This method provides several advantages such as simple work-up procedure, simple post-treatment process, high yields, broad applicability, practicability, and recycling of the catalyst.

■ Isoquinoline Alkaloids from the Twigs of Cassia fistula and Their Anti-Tobacco Mosaic Virus Activity

Hai-Yan Wu, Qiang Liu, Zhen-Hua Yu, Wei-Yao Hu, Ke-Liang Yan, Ye-De Wang, Kun Zhou, Wei Dong, Min Zhou,* and Qiu-Fen Hu*

*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 isoquinoline alkaloids, including a new natural product (1) and a compound (2) isolated from plant for the first time, and named fistulatins A and B (1 and 2), together with four known isoquinoline alkaloids (3-6) were isolated from the twigs of Cassia fistula. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-6 were tested for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that all isolates showed weak anti-TMV activity with inhibition rates in the range of 15.4-23.5%.

■ Antioxidant Effects of the Hydroxy Groups in the Simple Phenolic Carbazoles

Yuhzo Hieda, Noriyuki Hatae, Makoto Anraku, Nobuyasu Matsuura, Kazuhide Uemura, Satoshi Hibino, Tominari Choshi,* Hisao Tomida, Osamu Hori, and Haruto Fujioka*

*Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan

Abstract

Antioxidant activities of the simple phenolic carbazoles 5-11 were evaluated by 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azinobis-(3-ethylbenzthiazoline-6-sulfonate)+ radical scavenging assays. The simple phenolic carbazoles 5-7, 9, and 11 exhibited stronger antioxidant activities than α-tocopherol, and similar antioxidant activities as phenolic carbazole alkaloids carazostatin (1), and carbazomadurins A (3) and B (4). Bond dissociation energies and highest occupied molecule orbital energy levels of a series of phenolic carbazoles including phenolic carbazole alkaloids were calculated. The reducing ability of the phenolic carbazole core could be important role for the antioxidant activity of carbazole alkaloids 1, 3, and 4.

■ An Efficient One-Pot Synthesis of Azuleno[2,1-b]pyridazines

Dao-Lin Wang,* Jian Ma, Xiao-Ce Shi, and Jian-Ying Wu

*Liaoning Key Laboratory of Synthesis and Application of Functional Compound, College of Chemistry & Chemical Engineering, Bohai University, Jinzhou 121001, China

Abstract

A simple and efficient procedure was developed for the synthesis of 1-aryl-3-cyano-4-oxo-10-ethoxycarbonylazuleno[2,1-b]pyridazines (3) in good yields by condensation of ethyl 1-cyanoacetyl-2-methoxyazulene-3-carboxylate (1) with aryldiazonium salt (2) in pyridine via a domino reaction. This reaction provides a new procedure for synthesis of heterocyle-fused azulenes.