HETEROCYCLES

■ Contents

■ Three New Nervogenic Acid Derivatives from Liparis nervosa

Song-lin Wu, Chuan-lun Yang, Chun-gu Zhang,* and Shuai Huang*

*School of Life Science and Engineering, Southwest Jiaotong University, Southwest Jiaotong University, Chengdu, 610031, China

Abstract

In the present study, three new nervogenic acid derivatives (1–3) were isolated from the whole plant of Liparis nervosa (Thunb. ex A. Murray). Their structures were elucidated by extensive spectroscopic analyses including 1D, 2D NMR and HR-ESI-MS. The cytotoxicity of all the compounds was investigated against HCT116 human cancer cell line.

■ Diastereoselective Synthesis of Amide-Bridged Axially Chiral Biaryls through Point-to-Axial Asymmetric C-H Arylation

Qian Wang, Xiujuan Ma, Tingting Miao,* Jinjie Qian,* and Qian Shi*

*College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325000, China

Abstract

Amide-bridged axially chiral biaryls are important structural motif in natural products and pharmaceuticals. Herein we report a highly efficient C-H activation method to afford a novel kind of modifiable amide-bridged axially chiral biaryls. This approach has a broad scope, enabling the synthesis of various axially chiral biaryls with good reactivity and excellent diastereoselectivity. The axially chiral biaryl could be easily transformed to a new amide-bridged atropisomeric monophosphine ligand, which represent the high potential in asymmetric synthesis and catalysis.

■ An Efficient Synthesis of (Aryl)(4-(2-(arylethynyl)-phenyl)-1H-pyrrol-3-yl)methanone from the Reaction of (E)-1-Aryl-3-(2-(arylethynyl)phenyl)prop-2-en-1-one and p-Toluenesulfonylmethyl Isocyanide

Zhongwei Sun, Chengkai Wang, Fang Li, Zifeng Zhang,* and Liangce Rong*

*School of Chemistry and Materials Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan New District, Jiangsu, Xuzhou, China

Abstract

Herein we reported a facile approach to synthesize pyrrole derivatives under mild conditions. The reaction proceeds cycloaddition reactions between (E)-1-aryl-3-(2-(arylethynyl)phenyl)prop-2-en-1-one and commercially available p-toluenesulfonylmethyl isocyanide. Although the triple bond in the substrate was not involved in the reaction process, this work still provided a method for the synthesis of pyrrole derivatives. 

■ Supramolecular Chirogenesis in Amide-Linked Bis(Zinc Porphyrin): Application for Absolute Configurational Assignment of Chiral Calboxylic Acids and Chiral Amino Acids

Satoshi Hayashi,* Shiori Takeda, Takahiro Namba, Masahiro Noji, and Toshikatsu Takanami*

*Department of Life and Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A facile and derivatization-free method for determining the absolute configurations of a chiral carboxylic acid was developed by a supramolecular exciton-coupled circular dichroism (ECCD) protocol using the amide-linked bis(zinc porphyrin) BP2 as a hydrogen-bonding host molecule. Using a proposed working model, the stereochemistry of various carboxylic acids and N-protected amino acids can be determined nonempirically.

■ Access to Functionalized Pyrrolophenanthridine via an ortho C-H Amination/Interannular C-H Arylation Cascade of N-Arylpyrroles

Jitan Zhang,* Yuhang Li, Pengpeng Sun, Yue Zhang, Meihua Xie,* and Jiaping Wu*

*College of Chemistry and Materials Science, Anhui Normal University, 189 Jiuhua Nan Road, Wuhu, Anhui, 241002, China

Abstract

An expeditious access to pyrrolophenanthridine scaffold enabled by a Catellani strategy from N-arylpyrroles and O-benzoylhydroxylamines is disclosed. This reaction proceeds smoothly involving an ortho C-H amination/interannular C-H arylation cascade and well tolerates a number of pyrrole and amine substrates. Furthermore, the potential of this protocol has been highlighted by the easily accessible scale-up synthesis and a plausible mechanism of this reaction was also proposed.

■ FAB-MS Measurement of 2-Hydroxyestrone and Monosaccharides Assisted by 4-Pyridineboronic Ester Derivatization

Sachiko Komatsu, Katsuhiko Sato,* Kyoko Sugiyama, Masayuki Kumano, Kazuhiro Watanabe,* and Tsutomu Fujimura

*Laboratory of Synthetic and Medicinal Chemistry, Department of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

Phenylboronic acid (PBA) reacts specifically with diol compounds such as sugars. Compared with general derivatization, boronic ester derivatization has the advantage of being a simple procedure and requires fewer resources for sample pretreatment. To improve the detection sensitivity and selectivity for diol compounds in mass spectrometry, we investigated the effect of boronic ester derivatization of diol compounds on the detection sensitivity. As a result, several proton-affinitive boronic acids were examined, and the peak intensities of the ions associated with 2-hydroxyestrone were observed with 4-pyridineboronic acid as the reagent. The 4-pyridineboronic ester derivatization approach was found to be a useful labeling method for FAB-MS measurements due to the proton and diol affinity from the heterocyclic moiety.

■ Synthesis and Antitumor Activity of Novel Linear Tricyclic Compounds Derived from Purine

Hongmei Guo, Lifei Nie, Khurshed Bozorov, Haji Akber Aisa,* and Jiangyu Zhao*

*State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 40-1 South Beijing Road Urumqi, Xinjiang 830011, China

Abstract

Synthesis and antitumor activity of two series of novel linear tricyclic purine derivatives were reported. The structures of new compounds were characterized by 1H NMR, 13C NMR, HRMS (ESI). The inhibitory activities of the synthesized compounds were evaluated by conventional MTT assay against HT-29 human colorectal adenocarcinoma cell line, MCF-7 breast cancer cell line, and HeLa human cervical cancer cell. The compounds 5n~5q with long-chain alkane revealed the better inhibitory effect against all three kinds of cancer cells, while the compounds 4a~4l and 5a~5l with different substituted phenyl seemed to be more beneficial for the HeLa cell. Meanwhile, the toxicity of compounds 5m~5q against L-02 normal human liver cell was tested. The compound 5q showed promising antitumor activity in vitro against HT-29 (IC50 = 3.28 ± 0.57 μM), MCF-7 (IC50 = 7.13 ± 0.27 μM), and HeLa (IC50 = 14.24 ± 0.41 μM) cell lines and relatively low toxicity against L-02 (IC50 >100 μM) cell. The results suggested that compound 5q could serve as the promising antitumor lead compound for further research.

■ Microwave-Assisted Synthesis of Phenylisoxazole Derivatives via 1,3-Dipolar Cycloaddition

Yan Zhang, Zhiwu Long, Yi Le, Li Liu, and Longjia Yan*

*School of Pharmaceutical Sciences, Guizhou University, 440 Chongyi Building,Guizhou University, Huaxi District, China

Abstract

In this paper, an efficient method was developed to prepare phenylisoxazoles via metal-free microwave-assisted 1,3-dipolar cycloaddition reaction. Thirty derivatives were synthesized under the optimal condition and identified by NMR and HRMS. The yield was good from 30% to 93%.

■ Synthesis and in vitro Anticancer Efficacy of Novel Silibinin Derivatives

Jiang Zeng, Qiuchan Wu, Jinfu Dong, Cong Liang, Xiaomou Wei, Jifei Chen, Song Shi, Zhijie Yang, Tian Lan, and Hongwen Wu*

*Pharmacy, The Fourth Affiliated Hospital of Guangxi Medical University, No.1 Liushi Road, China

Abstract

A series of eleven novel silibinin derivatives bearing alkynyl or sulfonyl groups were successfully designed and synthesized, and most of them suppressed the proliferation of MCF-7, NCI-H1299, HepG2 and HT29 by CCK-8 assay. Especially 3a and 5b were determined to be the most effective derivatives in the tested series with IC50 values of 7.41 and 3.37 μM against MCF-7 and HepG2 cells, respectively. In addition, a structure-activity relationship (SAR) study revealed that monosubstituted derivatives exhibited more potent anticancer activity than multiple substituted derivatives. The proliferation inhibitory activity can be improved by oxidative dehydrogenation of silibinin derivatives. The present findings suggest C7-OH monosubstituted silybin or 2,3-dehydrosilibinin derivatives with alkynyl or sulfonyl groups would be promising for further development as an anticancer agent.

■ Concise Semi-Synthesis of a Flavone Glycoside from Marine Angiosperm

Lisha Wu, Shiqiang Yan,* and Limei Huang

*College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, Shandong 266042, China

Abstract

Starting from commercially available scutellarin, a natural flavonoid glycoside 6-hydroxyapigenin-7-O-(6”-O-(E)-coumaroyl)-β-glucopyranoside was semi-synthesized in a linear 6-step sequence with an overall yield of 31.5%. This work definitely laid the foundation for the further pharmacological study of this natural compound.

■ Characterization of Teaghrelin-Like Compounds from Tea Cultivars in Thailand and in silico Study of Their Bioactivity

Patcharee Pripdeevech, Sarunpron Khruengsai, Yue-Chiun Li, Chia-Hao Wang, Ping-Chung Kuo,* and Jason T. C. Tzen*

*School of Pharmacy, National Cheng Kung University, College of Medicine, 1, University Rd., Tainan, Taiwan, R.O.C.

Abstract

In the present research, four tea cultivars in Thailand were screening to search for the teaghrelin-like compounds and totally six components were identified. Among these, one new constituent isolated form Assam tea varieties was assigned as quercetin 3-O-[2-O-(E)-p-coumaroyl][α-L-rhamnopyranosyl(1→6)]-β-D-glucoside 4'-α-L-rhamnoside (1) through the comprehensive 1D- and 2D-NMR and mass spectrometric analysis. The isolated compounds were examined for their ghrelin receptor binding affinity in silico and antioxidant bioactivity by free radical scavenging model. However, no significant bioactivity was observed according to the experimental results.

■ Macrocarquinoid D, New Meroterpenoid from Brown Alga, Sargassum macrocarpum

Seiya Shinoda, Shin-ichiro Kurimoto, Takaaki Kubota, and Mitsuhiro Sekiguchi*

*Food analysis laboratory, Bioresources and Environmental Sciences, Food Science, Isikawa Prefectural University, 1-308, Suematsu, Nonoichi-shi, Ishikawa, Japan

Abstract

A new meroterpenoid, macrocarquinoid D (1) and 11 known meroterpenoids were isolated from brown algae, Sargassum macrocarpum. The structure of 1 was elucidated with NMR spectral data using 2D techniques. The DPPH radical scavenging and AGEs inhibitory activity of isolated compounds were examined.