HETEROCYCLES

■ Contents

■ Recent Progress in The Synthetic Study of an Antitumor Marine Macrolide Aplyronine A and Related Molecules

Ichiro Hayakawa* and Hideo Kigoshi*

*Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki 305-8571, Japan

Abstract

Aplyronine A is a potent antitumor marine macrolide. The unique molecular structures of aplyronine A and its congeners, in conjunction with their potent biological activities, have made them attractive synthetic targets. This review discusses recent progress in the development of efficient routes to the synthesis of aplyronines and the related molecules.

■ Synthesis of 1,5-Dioxaspiro[3.4]octane through Bromocation-Induced Cascade Cyclization

Atsuo Nakazaki, Yoshiki Nakane, Yuki Ishikawa, and Toshio Nishikawa*

*Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi 464-8601, Japan

Abstract

A new approach to the synthesis of 1,5-dioxaspiro[3.4]octane, spiro-oxetane having acetal moiety, via the bromocation-induced cyclization is described. This reaction underwent to furnish spiro-oxetane in one-pot manner with a high degree of diastereoselectivity.

■ A New Strategy for Synthesis of the Dinucleotide pdCpA: A Convenient Method for the Deprotection of Cyanoethyl, TBDMS, and Benzoyl Groups in One Step at High Pressure

Masanori Kataoka,* Chiharu Fukui, Akiko Mimoto, Hideaki Kuge, Koichi Honke, and Hiyoshizo Kotsuki*

*Laboratory of Natural Products Chemistry, Faculty of Science, Kochi University, 2-5-1, Akebono-cho, Kochi 780-8520, Japan

Abstract

A new improved method for the preparative-scale synthesis of the dinucleotide pdCpA was developed. This method takes advantage of the complete deprotection of cyanoethyl, TBDMS, and benzoyl groups in one step under high-pressure conditions in the final stage of the synthetic sequence.

■ Preparation of Acylthiophenes by Iron(III) Chloride Catalyzed Reactions of Tris(2-thienyl)stibanes with Acyl Chlorides

Naoki Kakusawa,* Yoshie Nakagawa, Yutarou Toshima, Shuji Yasuike, and Jyoji Kurita

*Faculty of Pharmaceutical Sciences, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan

Abstract

The reactions of tris(2-thienyl)stibanes with various acyl chlorides, using a catalytic amount of iron(III) chloride, afforded 2-acylthiophenes. Iron(III) chloride is presumed to act as a Lewis acid, and the ipso substituent of each 2-thienyl group of tris(2-thienyl)stibane is replaced with an acyl group. The reaction is highly atom-efficient in that all three thiophene rings of tris(2-thienyl)stibane take part in the reaction. The reaction procedure is so simple that it can also be carried out under solvent-free and aerobic conditions.

■ Two-Step Synthesis of 5-Hydroxy-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one Derivatives from 4-Chloro-6-methoxy-2-(methylsulfanyl)pyrimidine

Kazuhiro Kobayashi,* Ryoga Ono, Shohei Yuba, Hidetaka Hiyoshi, and Kazuto Umezu

*Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

We report a facile two-step procedure that allows the synthesis of the title fused heterocyclic derivatives from 4-chloro-6-methoxy-2- (methylsulfanyl)pyrimidine, readily available from 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP). The first step is the lithiation at the 5-position of the starting material with lithium diisopropylamide (LDA) and the reaction of the resulting lithium compound with α-keto esters to give the corresponding 2-hydroxy-2-(pyrimidin-5-yl)carboxylic acid ester derivatives. In the second step, these are treated with primary aliphatic amines in the presence of triethylamine to afford the desired products.

■ Triterpene Saponins from the Aerial Parts of Ilex cornuta and Their Cytotoxic Activity

Seung Young Lee, Won Se Suh, Ho Kyung Kim, Il Kyun Lee, Sang Un Choi, Ki Hyun Kim, and Kang Ro Lee*

*Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, 300 Chunchun-dong, Jangan-ku, Suwon 440-746, Korea

Abstract

Four new triterpene saponins (1-4), together with 13 known triterpenoids (5-17), were isolated from the MeOH extract of Ilex cornuta Lindley (Aquifoliaceae). Their structures were elucidated on the basis of chemical and spectroscopic methods. The isolated compounds were tested for their cytotoxicities against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) in vitro using the sulforhodamine B (SRB) assay.

■ Flavonoids from the Leaves of Sun Cured Tobacco and their Anti-Tobacco Mosaic Virus Activity

Yun Wang, Chun-Bo Liu, Qin-Peng Shen, Feng-Mei Zhang, Pei He, Zhi-Hua Liu, Hong-Bin Zhang, Xiao-Dong Yang, Ming-Ming Miao,* and Guang-Yu Yang*

*Key Laboratory of Tobacco Chemistry of Yunnan Province, China Tobacco Yunnan Industry Company, Hongjin Road 181#, Kunming, 650231, China

Abstract

Two new flavonoids, 4',6-dihydroxy-7,8-dimethoxyisoflavone (1), 8-acetyl-4'-hydroxy-7-methoxy-6-methylflavone (2), together with four known flavonoids (3-6) were isolated from the leaves of Yunnan local sun cured tobacco. 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) activities. Compound 2 showed high anti-TMV activity with inhibition rate of 35.4%. This rate is higher than that of positive control. The other compounds also showed potential anti-TMV activity with inhibition rates in the ranges of 18.5-22.3%, respectively.

■ An Efficient Construction of 4-Oxo-4H-chromene-2-carboxylate Derivatives via One-Pot Cascade Reaction Under Solvent-Free Conditions

Chao Huang,* Jia-Hui Guo, Huang-Mei Fu, Ming-Long Yuan, and Li-Juan Yang

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Engineering Research Center of Biopolymer Functional Materials, Yunnan Minzu University, 134 Yi Er Yi Avenue, Kunming, Yunnan, 650031, China

Abstract

An efficient synthetic strategy to chromone derivatives from commercially available diethyl acetylenedicarboxylate and phenols via a one-pot cascade reaction has been developed. Performing the reaction using pyridine and polyphosphoric acid as the catalyst at room temperature and 90 oC without any solvent gave the chromone derivatives in good to high yields at one time. A possible reaction pathway was also proposed and supported by the experiment. This protocol is environmentally friendly and metal-free, with advantages including short reaction times, convenient operation, and mild reaction conditions.

■ Synthesis and Cytotoxicity Activity of Some Novel Hydrazide, Pyrazole, Isoxazole, Pyrimidine and Fused Pyran-2-one Derivatives

Hala M. Refat* and Ahmed A. Fadda

*Faculty of Science, Department of Chemistry, Suez Canal University, Al-Arish, 45511, Egypt

Abstract

The reaction of 2-cyano-3-(dimethylamino)-N-((2-methoxynaphthalen-1-yl)methylene)acrylohydrazide (2) with some nitrogen nucleophiles, phenols and compounds, having an active methylene group to synthesis polyfunctionally substituted azoles (3-5), azine (6), fused azines (7-10) and fused pyran-2-one (11-17) derivatives. All the synthesized products were confirmed by elemental analysis, IR, 1H-NMR, 13C-NMR and MS data. The antitumor evaluation of the newly products against the four human tumor cells lines namely heptacelluar carcinoma (liver) HepG-2, Colorectal carcinoma (colon) HCT-116, mammary gland (breast) MCF-7 and Epdermoid carcinoma (larynx) Hep-2 was investigated. Compound 4 exhibited superior in vitro antitumor activity in the 3-cell lines assay.

■ Synthesis and Anticancer Activities of Thiazoles, 1,3-Thiazines, and Thiazolidine Using Chitosan-Grafted-Poly(vinylpyridine) as Basic Catalyst

Sobhi M. Gomha, Sayed M. Riyadh,* Elmahdi A. Mahmmoud, and Mahmoud M. Elaasser

*Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Abstract

Three different series of ethylidenehydrazonothiazoles 5a-c, 6a-c, ethylidenehydrazono-1,3-thiazines 9a-i and ethylidenehydrazonothiazolidine 12 have been prepared via reactions of ethylidenethiosemicarbazide 3a or ethylidenethiocarbohydrazide 3b with α-halocarbonyl compounds 4a-c, acrylonitrile derivatives 7a-i, and dimethyl acetylenedicarboxylate 10, respectively. Different basic catalysts were used in these reactions such as, triethylamine, chitosan, and chitosan-grafted-poly(vinylpyridine) and the latter catalyst has precedence as environmentally friendly basic catalyst. Moreover, the selected newly synthesized products were evaluated for their anti-cancer activity against a colon carcinoma cell line (HCT-116) and liver carcinoma cell line HEPG2 and revealed promising activity especially 1,3-thiazines 9c-i.

■ Synthesis of 3-Ethenylindoles via Intramolecular Cyclization of Aryl Radical with Allene Generated by Samarium(II) Diiodide

Kenji Suzuki, Hiroki Iwasaki, Fumihito Ichiyoshi, Mao Tominaga, Naoto Kojima, Minoru Ozeki, and Masayuki Yamashita*

*Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi, Yamashina, Kyoto, Japan

Abstract

N-(2,3-Butadien-1-yl)-N-(tert-butoxycarbonyl)-2-iodoanilines cyclized intramolecularly to form 3-ethenyl-2,3-dihydroindoles after treatment with samarium(II) diiodide. The dihydroindoles were easily oxidized to the corresponding 3-ethenylindoles in good to moderate yields.

■ Synthesis and Safener Activity of Novel Substituted 4-Phenoxyacetyl-1,4-benzoxazines

Fei Ye, Shi-Long Wu, Li-Xia Zhao, Hai-Tao Qu, Shuang Gao, and Ying Fu*

*Department of Applied Chemistry, College of Sciences, Northeast Agricultural University, No.59 Mucai Street Harbin 150030, Heilongjiang, China

Abstract

A novel class of 3-methyl-4-phenoxyacetyl-3,4-dihydro-2H-1,4-benzoxazine 3 were synthesized via reduction, cyclization, and acylation reactions. The structures of the compounds were characterized by IR, 1H-NMR, 13C-NMR, MS, and elemental analyses. The configuration of 3f was determined by X-ray crystallography. The bioassay results demonstrated that most of these compounds could alleviate 2,4-D butylate injury to maize.

■ New Anti-Oxidative Compounds from Rhinacanthus nasutus : HETEROCYCLES, 2015, 91, 1037 : DOI: 10.3987/COM-15-13193

Ryuichiro Suzuki,* Hiroshi Sakagami, and Yoshiaki Shirataki

*Pharmacognosy and Natural medicies, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan