HETEROCYCLES

■ Contents

■ The Reactivity of 8-Hydroxyquinoline and Its Derivatives Toward α-Cyanocinnamonitriles and Ethyl α-Cyanocinnamates: Synthesis, Reactions, and Applications of 4H-Pyrano[3,2-h]quinoline Derivatives

Ahmed M. El-Agrody* and Tarek H. Afifi

*Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt

Abstract

The main purpose of this review is to present a literature survey on the reactivity of 8-hydroxyquinoline and its derivatives toward α-cyanocinnamonitrile or ethyl α-cyanocinnamate derivatives, which leads to the formation of a variety of 4H-pyrano[3,2-h]quinoline derivatives. The reactions of the synthesized β-enaminonitriles and β-enaminoesters with different electrophilic followed by nucleophilic reagents were also explored. Some of these reactions provided successful routes to produce biologically important privileged structures.

■ Two New Clerodane Diterpenoids from Croton crassifolius

Wei-Huan Huang, Guo-Qiang Li, Jia-Gui Li, Xia Wu, Wei Ge, Hau Yin Chung, Wen-Cai Ye, Yao-Lan Li,* and Guo-Cai Wang*

*Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China

Abstract

The root of Croton crassifolius was evaluated for its anti-angiogenic properties and anti-angiogenic components. The ethanol extract of the herb and its successive four subfractions were investigated in zebrafish model by quantitative endogenous alkaline phosphatase assay. Both petroleum ether (PE) and ethyl acetate fractions (EtOAc) showed potent anti-angiogenic activities. Two new clerodane diterpenoids, crassifolin I (1) and crassifolin H (2) were isolated from EtOAc fraction. Their structures were elucidated by extensive spectroscopic methods (IR, UV, HRESIMS, 1D and 2D NMR), and compound 1 was confirmed by single-crystal X-ray diffraction analysis. The further activities study showed that crassifolin H possessed anti-angiogenic activity by reducing vessel formation to 59.3% of the control value at concentrations of 15 μg/mL.

■ Synthesis and Reactions of 2-Pyrido-Fused Bicyclic Compounds

Shang-Shing P. Chou* and Yi-Ting Wu

*Department of Chemistry, Fu Jen Catholic University, 510 Chung-Cheng Rd., Hsin-Chuang, New Taipei City 24205, Taiwan, R.O.C.

Abstract

Dihydropyridones derived from the aza-Diels–Alder reaction of 3-phenylthio-3-sulfolenes with p-toluenesulfonyl isocyanate (PTSI) gave readily the epoxy sulfones, which upon treatment with base afforded the 2-pyrido-fused bicyclic compounds. Some synthetic transformations of these compounds are also reported.

■ The Synthesis and Evaluation of New Carbocyclic Pyrrolo[2,3-d]pyrimidine Nucleoside Analogs

Jongbok Lee, Hyewon Seo, Sangeun Yoon, Kowoon Choi, Chul-Hoon Lee,* and Hakjune Rhee*

*Chemistry and Applied Chemistry, Department of Bionanotechnology, Hanyang University, 1271 Sa-3-dong, Sangrok-gu, Ansan, Kyunggi-do, 426-791, Korea

Abstract

New carbocyclic pyrrolo[2,3-d]pyrimidine nucleoside analogs were synthesized with the key intermediate, 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine (2), by SN2 reaction. One of the products, 4-amino-6-bromo-1-cyclopentyl-1H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (9), showed significant anti-proliferative activity to the human ovarian cancer PA-1 cells (IC50: 3.9 μM). Based on the biological effects and the functional group characteristics of the compound 9, other carbocyclic nucleoside analogs related to the compound 9 were synthesized with key intermediate 2 by a Pd(0)-catalyzed coupling reaction. As expected, syn-4-amino-6-bromo-7-[4-(methoxymethyl)-2-cyclopenten-1-yl]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (15) showed very similar anti-proliferative activity (IC50: 2.6 μM) when compared to compound 9.

■ Stereochemical Assignment of Four Diastereoisomers of 3,4-Dimethylpyroglutamic Acid, a Moiety of Callipeltin B

Mari Kikuchi and Hiroyuki Konno*

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

Abstract

The synthesis and stereochemical assignment of four diastereoisomers of 3,4-dimethylpyroglutamic acid (pDME) (1) are described. Stereo-divergent synthesis of four pDMEs (1) was achieved starting from Thottathil’s synthon and Garner’s aldehyde for comparison of synthetic pDMEs (1) by 1H NMR analysis and CD spectra. The stereochemistry of pDME (1) in cyclic depsipeptide callipeltin B (2) with cytotoxic and anti-HIV activities was confirmed to be 2S,3S,4R. Coupling constant between H2 and H3 of synthetic (2S,3S,4R)-pDME (1a) showed a smaller value than those of other isomers. In addition, synthetic pDMEs (1) hardly showed cytotoxicity against HeLa cells.

■ A Practical Synthesis of (4-(Spiro[chromane-2,4'-piperidin]-6-yl)phenyl)methanol as a Key Intermediate of Novel GPR119 Agonist

Tomoaki Koshizawa, Hayato Hosoi, Gen Watanabe, Toshiharu Morimoto, Tadaaki Ohgiya, and Kimiyuki Shibuya*

*Pharmaceutical Division, Tokyo New Drug Research Laboratories, Kowa Co., Ltd., 2-17-43, Noguchicho, Higashimurayama, Tokyo 189-0022, Japan

Abstract

Starting from commercially available 4'-hydroxy-[1,1'-biphenyl]-　4-carboxylic acid, a practical synthesis has been established in high yield for (4-(spiro[chromane-2,4'-piperidin]-6-yl)phenyl)methanol as a key intermediate for a novel GPR119 agonist.

■ The Synthesis of Dipyrazolylmethanes, X-Ray Structure Analysis

Yuan Ma, Jinxia Wang, and Hengchang Ma*

*Key Laboratory of Eco-Environment-Related Polymer Materials Ministry of Education, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China

Abstract

A small dipyrazoylmethane compounds library was established via the reaction of 5-alkyl- and 5-aryl-2-aryl-3H-pyrazol-3-ones with DMSO in the presence of NaOAc·3H2O as base using LiBr·H2O as additive at 100 oC.

■ A New Dihydrooxazole Antibiotic from the Fermentation Broth of Streptomyces djakartensis

Ji-Wen Zhang, Wen-Juan Zhang, Shao-Peng Wei, and Wen-Jun Wu*

*College of Science, Northwest A＆F University, Yangling 712100, Shaanxi Province, China

Abstract

A new antibiotic was isolated from the fermentation broth of Streptomyces djakartensis by bioassay-guided fractionation. It was elucidated as (S)-2-(2-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydrooxazole mainly by analyses of 2D NMR and MS spectral data and the absolute configuration of the antibiotic was established by X-ray crystal data. It exhibited broad spectrum antibacterial activities with MIC values of 7.81~31.25 μg/mL.

■ Speradines B-E, Four Novel Tetracyclic Oxindole Alkaloids from the Marine-Derived Fungus Aspergillus oryzae

Xiao Hu, Qi-Wen Xia, Yang-Yang Zhao, Qiu-Hong Zheng, Qin-Ying Liu, Li Chen,* and Qi-Qing Zhang*

*College of Chemistry and Chemical Engineering, Institute of Biomedical and Pharmaceutical Technology , Fuzhou University, No. 523, Gongye Road, Fuzhou City, 350002, China

Abstract

Four novel tetracyclic oxindole alkaloids, namely, speradines B (1), C (2), D (3), and E (4) were isolated from the marine-derived fungus Aspergillus oryzae. The structures of these compounds were elucidated through 1D and 2D nuclear magnetic resonance and high-resolution mass spectrometric analyses. Among these compounds, 1 and 4 showed weak cytotoxic effects on the hela cell line, with IC50 values of 57.2 and 73.4 μg/mL, respectively.

■ One-pot Synthesis of Novel Pyrano-Fused Coumarins Catalyzed by ZnO Nanoparticles

Saeed Khodabakhshi,* Bahador Karami, and Khalil Eskandari

*Department of Chemistry, Yasouj University, P.O.Box 353, Yasouj 75918-74831, Iran

Abstract

A new class of pyrano[3,2-c]coumarins containing an aryloylgroup was synthesized via the three-component reactions of 4-hydroxycoumarin with arylglyoxals and malononitrile. The reactions are efficiently catalyzed by zinc oxide nanoparticles as powerful and recyclable catalyst. The green chemistry principles were also considered and the present method has some advantages, such as simplicity, low catalyst loading, and high yields.

■ Selective Photocyclization Reactions of (Z)-N-Acetyl-α-dehydro(9-phenanthryl)alanine Alkyl Esters and N′,N′-Dialkylamides to Dibenzo[f,h]isoquinoline Derivatives

Yuto Iijima, Tetsutaro Igarashi, and Tadamitsu Sakurai*

*Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

(Z)-N-Acetyl-α-dehydro(9-phenanthryl)alanine alkyl esters and N′,N′-dialkylamides [(Z)-1] were synthesized, and their photocyclization behavior in methanol was explored. The irradiation of (Z)-1 in a protic polar solvent at wavelengths greater than 280 nm caused selective cyclization reactions, producing the corresponding dibenzo[f,h]isoquinoline derivatives. Moreover, the formation efficiency of these derivatives showed strong dependence on the steric bulk and electronic property of the alkoxycarbonyl and dialkylaminocarbonyl groups.

■ Synthesis of N,N-Dialkyl-5(or 10)-oxobenzo[b][1,8 or 1,7(or 1,6)]naphthyridine-10(5H)(or 5(10H))-carbothioamides Based on the Reaction of the Respective (Chloropyridinyl)(2-isothiocyanatophenyl)methanones with Secondary Amines

Kazuhiro Kobayashi,* Kazuhiro Nakagawa, and Hiroki Inouchi

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

Abstract

The addition of secondary amines to (2-chloropyridin-3-yl)(2-isothiocyanatophenyl)methanone, derived from 2-chloropyridine and N-(2-formylphenyl)formamide, followed by treatment of the resulting thiourea intermediates with sodium hydride has proven to provide a method for the synthesis of N,N-dialkyl-5-oxobenzo[b][1,8]naphthyridine-10(5H)- carbothioamides. Similarly, N,N-dialkyl-5-oxobenzo[b][1,7]naphthyridine-10(5H)-carbothioamides and N,N-dialkyl-10-oxobenzo[b][1,6]naphthyridine-5(10H)-carbothioamides can be prepared from the respective (chloropyridinyl)(2-isothiocyanatophenyl)methanones.