Regular & Special Issues

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Published online: 20th May, 2022

Communication | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)22
Synthesis of Benzo[d]Pyrrolo[1,2-a]imidazoles by Iminocyclopropane Rearrangement of C-Cyclopropyl Benzimidazoles

Adam P. Montoya, Matthew G. LaPorte, and Peter Wipf*

*Department of Chemistry, University of Pittsburgh, Pittsburgh PA 15260, USA


The MgI2 or NH4I mediated iminocyclopropane rearrangement of trisubstituted acrylonitrile benzimidazoles provides an attractive access to novel pyrrolo[1,2-a]imidazoles. The rearrangement precursors, C-cyclopropylbenzimidazoles, are obtained by a Corey-Chaykovsky cyclopropanation of the acrylonitrile. We determine the scope of the iminocyclopropane rearrangement to 2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole-3-carbonitrile and 2,4-dihydro-2,4-disubstituted as well as 1,2,4-trisubstituted 1H-benzo[d]pyrrolo[1,2-a]imidazole-3-carbonitriles, and describe some of the limitations and side reactions, including the formation of aromatized 4H-benzo[d]pyrrolo[1,2-a]imidazole-3-carbonitriles.

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Published online: 18th May, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14672
New Dimeric Cytisine-Type Alkaloid and Lavandulyl Biflavonoid from Sophora flavescens AIT. and Their Inhibitory Effect on Cancer Cells

Shengxue Chen, Yan Liu, Chenting Meng, Min Li, Chunping Yuan, and Xiaoying Yin*

*School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, China


Two new dimeric compounds with antitumor activity were extracted for the first time from Sophora flavescens Ait. using several chromatographic separation methods. Compound 1 (sophobikushenine) is a dimeric cytisine-type alkaloid connected by an eight-membered heterocycle ring, and compound 2 (sophobiflavanone) is a lavandulyl biflavonoid consisting of a skeleton including nitrogen atoms as heteroatoms. The structures of the two compounds were elucidated using one- and two-dimensional NMR, ECD, and HR-ESI-MS. The inhibitory effects of the new compounds against A431 and BT474 were evaluated in vitro implementing CCK-8 and scratch assays. Sophobiflavanone inhibited the growth of A431 cells with an IC50 value of 37.77 ± 0.98 μM and BT474 cells with an IC50 value of 38.13 ± 0.31 μM; further, it exhibited a strong antimigratory activity toward 4T1.

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Published online: 17th May, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14664
Facile Synthesis of Fully Conjugated Aminopyrazine Based Diazobenzenes and Diazoaminobenzenes with Aryldiazonium Salts

Idris Karakaya*

*Department of Chemistry, College of Basic Sciences, Gebze Technical University, 41400 Gebze, Turkey


Herein, we report the diazotization of aminopyrazine achieved in good to excellent yields using electronically disparate aryldiazonium salts at room temperature. These novel and fully conjugated diazobenzenes and diazoaminobenzenes were characterized utilizing NMR, HRMS, single crystal X-ray diffraction, and UV–Vis techniques. Depending on the position of the functional groups substituted on the aryldiazonium salts and their ability to forge hydrogen bonds, these reactions can diverge into two possible pathways to give diazobenzenes or diazoaminobenzenes selectively. Based on the results of UV-Vis spectroscopic analysis, it was determined that the maximum absorbance band of the compounds was between 333 nm and 363 nm due to their interacting π-π* transitions. These results are further supported by DFT calculations, showing these molecules exhibit high absorbance.

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Published online: 16th May, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14666
Ultrasound Assisted One Pot, Three-Component Reaction for Facile Design of Novel 1,2,3-Diazaphosphole, 1,5,2-Diazaphosphinine and 1,5,2-Diazaphosphepine Compounds Containing Coumarin Ring

Tarik E. Ali,* Mohammed A. Assiri, Abdullah Y. Alzahrani, and Mohamed A. Salem

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo, Egypt


We have designed novel 1,2,3-diazaphosphole, 1,5,2-diazaphosphinine and 1,5,2-diazaphosphepine compounds containing a coumarin ring. The method depended on one-pot, three-component reaction of 3-(2-bromoacetyl)-2H-chromen-2-one (1) and diethyl phosphite in the presence of diamine reagent under ultrasonication effect at 50 oC. The possible reaction mechanisms of the formation of these products were displayed and discussed. The structures of isolated products were established by elemental analyses and spectral tools.


Published online: 16th May, 2022

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14669
Antimicrobial Acetophenone and Phenalenone Derivatives from a Soil-Derived Fungus Penicillium Verrucisporum JX1

Huiping Hu, Yuting Tang, Hengyi Lin, Zheng Ma, Penglai Fan, Xiachang Wang, Yongyong Zhang,* and Jiarong Pan*

*Key Laboratory of Marine Food Quality and Hazard Controlling Technology of Zhejiang Province, College of Life Sciences, China Jiliang University, Hangzhou 310018, China


A new acetophenone derivative, named veracetophenone (1), along with six known compounds communol F (2), clavatol (3), (+)-scleroquinone (4), (‒)-trypethelone (5), (‒)-sclerodin (6), and (‒)-scleroderolide (7), were isolated from a soil-derived fungus Penicillium verrucisporum JX1. Their structures were identified on the basis of spectral analysis of 1D, 2D-NMR, and HRESIMS. The configuration of 4 was depicted based on spectroscopic data as well as optical property. Their antibacterial and antifungal activities were also evaluated.

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Published online: 12th May, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14676
Synthesis and Antimicrobial Activity of 2,5-bis(Pyrazol-3-yl or Triazol-4-yl)-1,3,4-oxadiazoles

Hanan A. Mohamed, Bakr F. Abdel-Wahab, Eman Sabry, Benson M. Kariuki, and Gamal A. El-Hiti*

*Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia


The reaction of pyrazole-3-carbohydrazide (1) or 1,2,3-triazole-4-carbohydrazides 5a,b and 2-(ethoxymethylene)malononitrile (2) in ethanol under reflux conditions afforded the corresponding N,N'-diacylhydrazines 3 or 6a,b, respectively in high yields. Ring closure of 3 or 6a,b in the presence of phosphorus oxychloride furnished the corresponding 2,5-bis(heterocyclic)-1,3,4-oxadiazoles 4 or 7a,b, respectively in good yields. The synthesized heterocyclic compounds showed moderate activity against Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli.


Published online: 9th May, 2022

Paper | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)19
N-Heterocyclic Analogs of Indenocorannulene

Ansu Li, Jun Xu, Kim K. Baldridge, and Jay S. Siegel*

*School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, China


Four chiral N-heterocyclic monoindenocorannulenes were prepared by fusing pyridine, quinoline, and indole across the peri positions of corannulene via tandem Suzuki-aryl-aryl coupling and C-Cl activated ring closure reactions. The UV-Vis, fluorescence, and CV properties of these N-doped polynuclear aromatics are discussed. Resolution of enantiomers is performed on chiral stationary phase HPLC and the absolute configurations are assigned by comparison of experimental and quantum mechanically predicted ECD spectra.

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Published online: 27th April, 2022

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14644
Synthesis, Characterization and Biological Screening of New N-Substituted-7-chloro-4-hydroxy-2-quinolone-3-carboxamides as Promising Anticancer Agents

Aya Mohammed kheir Al-Zuheiri, Kamal Sweidan,* Mohammed Kamal Harb, Sanaa K. Bardaweel, Mahmoud Sunjuk, and Dima A. Sabbah

*Department of Chemistry, The University of Jordan, Amman 11942, Jordan


A new set of 7-chloro-4-hydroxy-2-quinolone-3-carboxamide derivatives has been synthesized in good yields by using simple procedure. The prepared compound has been characterized using different spectroscopic techniques including high resolution mass spectrometry (HRMS), infrared spectroscopy (IR), one-dimensional (1D), two-dimensional (2D) nuclear magnetic resonance (NMR), and by elemental analysis (EA). The target products have been tested as anticancer agents against cell lines; human colon carcinoma (HCT-116), breast adenocarcinoma (MDA-231), epithelial colorectal adenocarcinoma (Caco-II), and normal cell lines. Results indicated that compound demonstrated selective inhibitory activity; compound 14 exerted high activity against HCT-116 cell line (IC50 = 87.45 µM), compound 5 exhibited high activity against (MDA-231) cell line (IC50 = 23.66 µM), and compound 10 demonstrated high activity against (Caco-II) cell line (IC50 = 35 µM).

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Published online: 27th April, 2022

Review | Special issue | Prepress
DOI: 10.3987/REV-22-SR(R)8
Sparsomycin – a Review and Re-Assessment

Geoffrey A. Cordell* and Sharna-kay Daley

*Natural Products Inc., Evanston, IL, 60202, U.S.A.


The chemistry, biology, and biosynthesis of the microbial alkaloid sparsomycin (1) are summarized and re-assessed to identify future research initiatives for this biologically significant metabolite.


Published online: 26th April, 2022

Paper | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)20
Synthesis of 1-Azaspiro[4,5]-7-decen-2-one from L-Asparagine and L-Aspartic Acid

Punlop Kuntiyong,* Sunisa Moongmai, Natida Thongluar, and Ittiphat Klayparn

*Department of Chemistry, Faculty of Science, Silpakorn University, Sanamchandra Palace, Muang Nakhon Pathom 73000, Thailand


A synthetic strategy for 1-azaspiro[4.5]-7-decen-2-one based on N-acyliminium spirocyclization is reported. The common core structure found in biologically active alkaloids such as FR901483, TAN1251 and lepadiformine was synthesized via chiral N-alkyl-3-dibenzylaminosuccinimide intermediates. The chiral succinimides were synthesized in 2 steps from L-aspartic acid or 3 steps from L-asparagine.

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Published online: 25th April, 2022

Paper | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)17
2-Arylazoimidazoles Revamped by Quarternization or Dimerization; Another Gain in Functionality of an Industrial Dyestuff Family by Task-Specific Side-Chain Substituents

Sandro Neuner, Heidi A. Schwartz, Christoph Kreutz, Thomas Müller, Paul Mayer, Günther Bonn, Thomas Gelbrich, Ulrich J. Griesser, Klaus Wurst, Volker Kahlenberg, Sven Nerdinger,* and Herwig Schottenberger*

*Sandoz GmbH, Biochemiestr. 10, 6250 Kundl, Austria


Based on [(E)-2-(4-fluorophenyl)diazenyl]-1H-Imidazole,[210180-24-0], a versatile late stage intermediate for the divergent synthesis of direct dyes, a novel series of N,N`-disubstituted azoimidazolium salts was prepared. In particular, benzylation, 4-vinylbenzylation, phenacylation, sulfopropylation, ethylation, as well as propargylation allowed for the access of derivatives (1-6), which are useful for follow-up conversions, e.g. click reactions, or free radical polymerization. The compounds were routinely characterized spectroscopically. The diethylated tetrafluoroborate salt 5 was additionally analyzed by 19F-NMR. Hot stage microscopy of contact melts of 5 with the less commonly used anionic nucleophiles azide and rhodanide illustrate the rapid formation of deeply colored products confirming the nucleophilic aromatic replacement of fluoride in the 4-fluorophenyl substituent. Remarkably, in addition to the conceived functional quarternizations, a neutral dimer chromophore (7) resulted from using epichlorohydrin as a linking agent. Single crystal X-ray structure determinations are reported for all newly described compounds.

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Published online: 22nd April, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14652
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


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.

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Published online: 22nd April, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14641
Synthesis and Optical Properties of Substituted 5,6,7,8-Tetraaza-azuleno[1,8-b,c]fluorenes, Small Organic Molecules of Unusual Topology Designed for Circularly Polarized Luminescence

Tadeusz Lemek,* Krzysztof Danel, Oskar Michalski, and Wojciech Nitek

*Tadeusz Lemek; R&D Institute of Celon Pharma S.A., ul. Marymoncka 15, 05-152 Kazuń Nowy, Poland


Helical photoluminescent substituted 5,6,7,8-tetraaza-azuleno[1,8-b,c]fluorenes were obtained as racemates. The compounds have been designed for circularly polarized luminescence. Some of the compounds were separated on to enantiomers with chiral HPLC column and showed Cottons effects in absorption and emission spectra. The experimental results were compared with DFT calculations, which led us to assess the chirality to structure.

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Published online: 22nd April, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14658
Efficient Synthesis of Novel Spiro[indoline-3,5'-pyrano[2,3-d]pyrimidin]-2-one Derivatives and Antitumor Activity Evaluation

Zhenhua Li,* Guoqing Huang, Dayou Rong, Yingyan Cao, and Ronghui Hu

*College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, P.R. China


An efficient method for synthesis of the spiro-[indoline-3,5'-pyrano[2,3-d]pyrimidin]-2-one derivatives from 2'-amino-2-oxo-spiro[indoline-3,4'-pyran]-3'-carbonitriles using bis(trichloromethyl) carbonate (BTC) and triphenylphosphine oxide (TPPO) was developed. A series of target compounds with broad substrate scope were synthesized in moderate to good yields. In addition, the antitumor activities against four cancer cell lines A549, HepG-2, MCF-7, and HeLa were evaluated using 5-FU and cisplatin as reference, all compounds showed good antitumor activity compared with the standard drugs.

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Published online: 20th April, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14659
Synthesis of 2-Trifluoroacetonyl-3-alkyl/alkoxychromones and Their Reactions with 1,2-Bidentate Nucleophiles

Iryna M. Biletska, Galyna P. Mrug, Yaroslav O. Prostota, Kostyantyn M. Kondratyuk, Svitlana P. Bondarenko, and Mykhaylo S. Frasinyuk*

*V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of National Academy of Science of Ukraine, Kyiv 02094, Ukraine


The reaction of 3-substituted 2-methyl/2-benzyl/2-(2-phenethyl)chromones with trifluoroacetic anhydride in presence of potassium trifluoroacetate was investigated. It was established that the nature of substituent in position 3 of chromone ring has no crucial influence/limitation on this reaction, whereas only in the case of 2-benzyl substituent (in addition to 2-sec-alkyl group) no reaction was occurred at all. Reaction of synthesized 2-(3,3,3-trifluoro-2-oxopropyl)chromones with hydrazine dihydrochloride afforded 3-(2-hydroxyphenacyl)-5-trifluoromethylpyrazoles, but reaction with hydroxylamine led to oximation of side-chain carbonyl group. Reaction of 2-trifluoromethylchromones with 1,2-bidentate nucleophiles led to substituted 2-hydroxyphenylpyrazoles and isoxazoles. Mechanisms of these ring-transformation reactions are discussed.

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Published online: 14th April, 2022

Paper | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)13
Synthesis of Novel Fluorescent Bicyclic Amidines and Evaluation of Their Photophysical Properties

Wannaporn Disadee,* Kittiporn Trisupphakant, and Somsak Ruchirawat

*Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Lak Si, Bangkok 10210, Thailand


A metal-free process for the synthesis of novel bicyclic amidines was developed. The key conversions involved a cascade of double intramolecular cyclization of Michael adducts under a mild condition to provide 39 analogs in up to 93% yield. Photophysical properties of the representatives, a parent molecule and its free base form were studied on different solvents. From the results, a free base form exhibited strong fluorescent emission wavelength in up to 491 nm and large Stoke shift in up to 140 nm, offering positive information for their future development.

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Published online: 14th April, 2022

Review | Special issue | Prepress
DOI: 10.3987/REV-22-SR(R)9
The Xanthate Route to Benzazepinones and Their Aza Congeners

Béatrice Quiclet-Sire and Samir Z. Zard*

*Department of Chemistry, Ecole Polytechnique, CNRS UMR 7652, 91128 Palaiseau, France


The present brief overview highlights and discusses the synthetic potential of the degenerative radical addition of xanthates for the synthesis of benzazepinones and their aza congeners. Various routes are presented, including direct cyclisations onto the aromatic or heteroaromatic ring, intermolecular radical additions followed by ring closure, and Beckmann ring expansion of tetralones produced by radical addition-cyclisation. Many of the compounds described are medicinally relevant and not readily available by more conventional methods.


Published online: 13th April, 2022

Communication | Regular issue | Prepress
DOI: 10.3987/COM-22-14649
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


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.

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Published online: 12th April, 2022

Communication | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)18
Synthesis and Stereochemical Analysis of Planar Chiral Nine-Membered Aza-Orthocyclophyne

Yuuya Kawasaki, Sumire Tanaka, Kazunobu Igawa, and Katsuhiko Tomooka*

*Institute for Materials Chemistry and Engineering, Department of Molecular and Material Sciences, and IRCCS Kyushu University, Kasuga, Fukuoka 816-8580, Japan


Aza-orthocyclophyne 3b with an oxy-substituent on the 16 position of the benzene ring was synthesized, and it was revealed that the stereochemical stability of 3b is consistent with the order of 1,3-steric repulsion between the C2 methylene protons and the oxy-substituent.

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Published online: 12th April, 2022

Paper | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)21
Oxidative Fragmentation of Cytisine as an Entry to the Bis(piperidine) Scaffold of Virgidivarine

Worawat Niwetmarin* and Timothy Gallagher*

*School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom


Using virgidivarine as a focus, we have extended the oxidative fragmentation of (-)-cytisine as a source of functionalized heterocyclic fragments to provide a novel bis(piperidine) 2-epivirgidivarine. This stereochemically-defined scaffold offers synthetic versatility within an “sp3-rich” environment that makes it amenable to further manipulation and development within the context of de novo drug design.

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Published online: 11th April, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14633
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


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

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Published online: 11th April, 2022

Communication | Regular issue | Prepress
DOI: 10.3987/COM-22-14646
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


In the present study, three new nervogenic acid derivatives (13) 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.

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Published online: 7th April, 2022

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)14
Synthesis and Cytotoxic Activity of Wrightiadione and Its Derivatives

Sanit Thongnest and Jutatip Boonsombat*

*Chulabhorn Research Institute, Bangkok 10210, Thailand


A synthetic method for generating the tetracyclic isoflavone wrightiadione was developed through a Friedel-Crafts acylation of isoflavone-2-carboxylic acid. A series of wrightiadione derivatives was conveniently synthesized by this approach and evaluated for cancer cytotoxic, cancer chemopreventive, and antimalarial properties. Some derivatives exhibited potent cancer cytotoxic activity at the single-digit micromolar level.

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Published online: 6th April, 2022

Review | Special issue | Prepress
DOI: 10.3987/REV-22-SR(R)7
Five-Membered Nitrogen Heterocycles as New Lead Compounds in Drug Discovery

Agustono Wibowo, Mohd Fazli Mohammat, Zurina Shaameri, Fatin Nur Ain Abdul Rashid, Noor Hidayah Pungot, and Ahmad Sazali Hamzah*

*Organic Synthesis Laboratory, Institute of Science, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia


Five-membered nitrogen heterocyclic compounds are a very important group with various pharmaceutical properties. The different substitutions and functionalization of these compounds contributed to various biological activities. Five-membered nitrogen heterocyclic scaffolds are used for synthesizing numerous natural and synthetic compounds with a significant biological application. They include antidiabetic, anticancer, antimalarial, antiviral, antimicrobial, anti-inflammatory, antibacterial, and anti-neurodegenerative agents. This mini-review provides an overview of the biological activities and the synthetic methods for preparing the five-membered nitrogen heterocyclic scaffolds and their functionalization. In the final part, this mini-review also listed some commercial drugs containing five-membered nitrogen heterocyclic motifs, highlighting the versatility of the five-membered nitrogen heterocyclic core in drug discovery.


Published online: 6th April, 2022

Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14654
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


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%.

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Published online: 5th April, 2022

Review | Special issue | Prepress
DOI: 10.3987/REV-22-SR(R)6
8-Hydroxyquinolines: A Promising Pharmacophore Potentially Developed as Disease-Modifying Agents for Neurodegenerative Diseases: A Review

Veda Prachayasittikul,* Ratchanok Pingaew, Supaluk Prachayasittikul, and Virapong Prachayasittikul

*Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand


8-Hydroxyquinoline (8HQ) is an attractive heterocyclic scaffold with well-known metal chelating property, broad-ranging pharmacological activities, and preferrable drug-likeness, thus, it had gained a continual attention in areas of drug development, especially, drug repurposing. Alzheimer’s disease (AD) is one of globally health concern in an era of aging society and its management is considered challenging as effective disease-modifying drugs are still clinically unavailable. Loss of metal ion homeostasis is one of key factors contributing to pathogenesis and progression of AD in which its imbalance could trigger many related key factors and harmful events, especially, oxidative neuronal damages. Hence, restoration of homeostasis and distribution of brain’s metal ions served to be a promising strategy for development of disease-modifying agents. In this review, essential key points relating to AD pathogenesis, roles of metal ions in AD, and pioneer 8HQ-based compounds are introduced. A series of recently reported 8HQ-based neuroprotective compounds (i.e., derivatives, hybrids, conjugates, and metal complexes) focusing on compounds acting as metal chelators are reviewed. Related 8HQ-based neuroprotective compounds with other mechanisms of actions are also discussed. Additionally, summary of key contents is included to provide an overview of current development situations. Taken together, this article would be beneficial and inspiring for the related future drug design and development to tackling an increasing prevalence of neurodegenerations in the global aging society.


Published online: 5th April, 2022

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-22-14651
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


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.

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Published online: 1st April, 2022

Review | Special issue | Prepress
DOI: 10.3987/REV-22-SR(R)4
1,2,3-Triazole Scaffold in Recent Medicinal Applications: Synthesis and Anticancer Potentials

Vanida Choomuenwai,* Ronnakorn Leechaisit, Ratchanok Pingaew,* Veda Prachayasittikul, Supaluk Prachayasittikul, and Virapong Prachayasittikul

*Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand


Cancer is one of commonly concerned health problems globally and its management is challenging. Besides an availability of diverse classes of anticancer agents, the existing drugs are noted for their limitations such as considerable toxicities, low potency and responsiveness, drug resistance, and others. 1,2,3-Triazole is an attractive heterocyclic scaffold possessing considerable characteristics and is presented in many pharmacologically active molecules. Accordingly, attention has been given to this scaffold in the recent years, especially, in an area of anticancer drug development. In this review, a collection of recently reported triazole based anticancer agents are discussed along with their synthetic methods, proposed molecular targets, and mechanisms of actions. A summary of other recently reported biological activities is also provided. In overview, recent studies suggested that the 1,2,3-triazole based compounds could elicit their anticancer effects against several cancer cell lines via an inhibition of cancer cell growth, an induction of apoptosis, an inhibition of involved enzymes such as aromatase, kinases, and others. Some interesting results from computational studies also discussed relating to the predictions of possible molecular targets. In summary, it is suggested that the 1,2,3-triazole serves as a potential scaffold with noteworthy opportunity for future development of novel anticancer agents to cope with current challenging issues in cancer management.


Published online: 1st April, 2022

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)12
Asymmetric Intramolecular Aldol Reactions Mediated by Chiral Triamines Bearing a Pyrrolidine Scaffold to Provide a Wieland–Miescher Ketone

Yuichi Akahane and Kohei Inomata*

*Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara 324-8501, Japan


We established a new asymmetric route to provide (R)-Wieland–Miescher ketone [(R)-2] using a combination of trifluoroacetic acid (TFA) and known or new chiral triamines (7) bearing a pyrrolidine scaffold. Although the intramolecular aldol reaction of trione (1) mediated by chiral prrolidine (7) resulted in the production of 2 with low enantioselectivities, a remarkably increased enantioselectivity with a combination of 7b or 7c and TFA was observed. We also found that a secondary amine motif existing in the middle of the side chain was important in defining the enantioselectivity.


Published online: 31st March, 2022

Paper | Special issue | Prepress
DOI: 10.3987/COM-22-S(R)11
Novel Syhthesis and Property of Optically Pure N-Trifluoroacetylphenylglycine Hydroxysuccinimide Ester

Zeping Wang, Shoko Ishikawa, Fumina Ohashi, Reo Sagisaka, Yuta Murai, Zetryana Puteri Tachrim, Takeyuki Suzuki, and Makoto Hashimoto*

*Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Hokkaido, Japan


Phenylglycine is non-proteinogenic α-amino acid, and its partial structure is found in some biologically active compounds. C-Terminal modification of N-acyl-protected phenylglycine sometimes causes racemization due to the fact that the phenyl ring is directly connected to the α-position of the α-amino acid skeleton. In this report, synthesis and the property of N-trifluoroacetylphenylglycine hydroxysuccinimide ester was archived.

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