HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Regular Issue
Vol. 106, No. 12, 2023
Published online: 10th November, 2023
■ Synthesis of Thiosemicarbazone Derivatives of 3-Formyl-N-pyrazolylmethyleneindoles and Their Antifungal Activities
Tianze Li, Min Lv,* and Hui Xu*
*college of Plant Protection, Northwest A&F University, Xinong road 22#, China
Abstract
In order to discover natural-product-based antifungal candidates, a series of new thiosemicarbazone derivatives of 3-formyl-N-pyrazolylmethyleneindoles were prepared. Some derivatives showed good antifungal activities. Against Curvularia lunata, compound I-2 showed 2.2 times antifungal activity compared to the precursor indole. Against Valsa mali, compound Ⅰ-1 exhibited 1.7 times antifungal activity compared to indole.
Published online: 2nd November, 2023
■ Synthesis, Characterization, Molecular Docking Studies and Antimicrobial Activity of Azomethine Derivatives of 1,3-Substituted Pyrazoles
Hissana Ather,* Aysha A. Ali Theban, Fareeaa Ashar, Boshra Yahya A. Mohamed Essa, Yomna Ali A. Albarqi, Ghadah Saad A. Alshehri, and Renad Abdulhadi M. Almodawi
*Pharmaceutical Chemistry Department, King Khalid University, King Khalid University, Abha, Saudi Arabia
Abstract
Two different series of azomethine derivatives of 1,3-substitued pyrazoles were synthesized from the intermediates 3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3a) and 3-(furan-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3b) by the condensation of various substituted anilines. The intermediates were obtained from the appropriate phenylhydrazones via Vilsmeier–Haack reaction. The synthesized compounds were characterized by IR, 1H NMR and MASS spectral studies. Molecular docking studies results revealed that 4a7 and 4a8 showed highest binding affinity against fungal target secreted aspartic proteinase (Sap) 1 (2QZW) and compounds 4a8 and 4a5 showed highest binding affinity against bacterial target glucosamine-6-phosphate synthase (2VF5). In vitro antimicrobial activity of corresponding azomethine derivatives were assessed on Gram-positive and Gram-negative bacteria. Antifungal activity was assessed on Candida albicans. The results revealed that six out of fifteen compounds screened have shown good antimicrobial activity. Among them, 4a1, 4a4, 4a6 and 4a7 shown good inhibition against Candida albicans.
Published online: 1st November, 2023
■ Diastereoselective Synthesis of 2,8-Dioxabicyclo[3.3.1]Nonane Derivatives via I2-Mediated Cascade Reactions
Dong Cheng, Xiangzhen Meng,* Yang Li, and XinRun Ji
*School of Chemical Engineering and Life Science, Chaohu College, Chaohu Anhui, Peoples 238000, China
Abstract
The highly diastereoselective one-pot synthesis generating a variety of 9,9-dimethyl-2,8-dioxabicyclo[3.3.1]nonane derivatives up to dr >19:1 has been established by the reaction of a 2’-methoxylchalcone with isobutyraldehyde via a spontaneous sequential one-pot Michael addition/aldol reaction/demethylative bicyclization in the presence of molecular iodine.
Published online: 6th November, 2023
■ Synthesis of Hepta-arbutin-branched β-Cyclodextrins at their Primary Sides via Click Reaction
Yoshiki Oda,* Junki Nakagawa, and Takashi Yamanoi*
*Technology Joint Management Office, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan
Abstract
This paper describes the synthesis of β-cyclodextrin (CD) based arbutin (4-hydroxyphenyl β-glucopyanoside) conjugates as a model for drug delivery molecules. We introduced three variants of hepta-arbutin-branched CDs at their primary side. Of these, two incorporated oligo(ethylene)chains within their spacers to demonstrate the effect of varying spatial characteristics between the β-glucopyanoside moieties. Due to the sterically hindered position on the primary side of β-CD, we employed a highly efficient click chemistry reaction.
Published online: 18th October, 2023
■ A Facile Synthesis and Anticancer Activity of (E)-Diethyl 2-Styrylquinoline-3,4-dicarboxylates
Shuling Liu, Jing Wang, Yang Li,* and Yu Chen*
*Institute of Superfine Chemicals, Bohai University, 19 Keji Road, Jinzhou 121000, China
Abstract
In the present investigation, a simple and flexible synthesis of a series of novel (E)-diethyl 2-styrylquinoline-3,4-dicarboxylates 3a-q has been achieved for the first time in good yields, involving one-pot sequential Arbuzov/Horner–Emmons reaction sequence using the newly-synthesized diethyl 2-(bromomethyl)quinoline-3,4-dicarboxylate as the substrate. The latter was obtained by NBS-mediated radical bromination reaction of the readily available diethyl 2-methylquinoline-3,4-dicarboxylate. A primary in vitro evaluation for their antiproliferative activity against human cancer cell lines (A549, HT29 and T24) revealed that the compound 3k with 3,4,5-trimethoxystyryl moiety represented the most active molecule against the tested A549 cell lines in this round of effort with the IC50 values of 2.38 µmol•L-1, being higher than the reference cisplatin.
Published online: 24th October, 2023
■ Synthetic Studies toward 11-O-Debenzoyltashironin
Hisahiro Hagiwara*
*Graduate School of Science and Technology, Niigata University, 8050, 2 no-cho, Ikarashi, Niigata 950-2181, Japan
Abstract
11-O-Debenzoyltashironin is a highly oxygenated allo-cedrane sesquiterpenoid with seven contiguous chiral centers in a compact fused ring, and shows remarkable neurite extension activity. Total syntheses of the title and related compounds are reviewed.
Published online: 30th October, 2023
■ Briastecholide N: A New Chlorine-Containing Briarane Diterpenoid Deriving from Cultured Briareum Stechei
You-Ying Chen, Yueh-Wen Liu, Su-Ying Chien, Yu-Cheng Chen, Fu-Ching Chiu, Po-Wei Huang, I-Li Su, Zhi-Hong Wen, Hung-Tsung Lee,* and Ping-Jyun Sung*
*Department of Planning and Research, National Museum of Marine Biology and Aquarium, 2 Houwan Road, Checheng, Pingtung, Taiwan 944, Taiwan
Abstract
A new chlorine-containing briarane-type diterpenoid, briastecholide N (1) was isolated from cultured octocoral Briareum stechei via chemical screening. The structure of 1 was corroborated by 2D NMR experiments and confirmed backed by single-crystal X-ray diffraction analysis. The study found that 1 is capable of increasing the release of alkaline phosphatse (ALP) at 10 μM.
Published online: 2nd November, 2023
■ Synthesis of New Glycoluril Derivatives via Ring-Closing Metathesis
Sambasivarao Kotha* and Deepshikha Singh
*Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India
Abstract
Tetra-N-allylation of glycoluril reactions followed by ring-closing metathesis has been used to generate new concave-shaped glycoluril derivatives. The advantages of this method are mild conditions, single-product formation and good yield.
Published online: 16th November, 2023
■ Synthesis of Protected L,L-Cyclotryptophyltyrosine, A Key Unit of Tryptorubin A
Ryohei Nokura, Mayu Senda, Haruhiko Fukaya, and Yukio Hitotsuyanagi*
*Department of Natural Products and Medicinal Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
A protected form of L,L-cyclotryptophyltyrosine, a key structure of the bicyclic hexapeptide tryptorubin A isolated from Streptomyces sp. CLI2509, was synthesized. Treatment of Boc-L-Trp-3-borono-L-Tyr(Me)-OMe, obtained from the coupling reaction of Boc-L-Trp-OH and H2N-3-iodo-L-Tyr(Me)-OMe and the subsequent borylation of iodide, with Cu(OAc)2, pyridine, and 4 Å molecular sieves in dichloromethane at 30 °C for 48 h at a concentration of 0.001 M gave protected L,L-cyclotryptophyltyrosine in 58% yield. The structure of obtained protected L,L-cyclotryptophyltyrosine was confirmed by X-ray crystallography, revealing the presence of a pyramidal indole nitrogen atom.
Published online: 6th November, 2023
■ Synthesis, Antioxidant Activity and Molecular Docking of Some New Thiazolyl-Pyrazolinyl-Pyran-2-One Derivatives
D. Hikem-Oukacha, S. Tellal, A. Amar, K. Ould Lamara, A. Rabahi, A. Benazzouz, S. Bouaziz-Terrachet, M. Makhloufi-Chebli, B. Jismy, and M. Abarbri*
*Chemistry, University of Tours, Faculté des Sciences et Techniques. Parc de Grandmont, France
Abstract
3-[2-(5-Aryl-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4-yl]-4- hydroxy-6-methyl-2H-pyran-2-ones 6a-h were synthesized via the ring closure reactions of 3-phenyl-5-aryl-4,5-dihydropyrazole-1-carbothioamides 3a-h with 3-(bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one 5. The new synthesized thiazolyl-pyrazolinyl-pyran-2-one compounds were evaluated for their potential antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method. The molecular docking of the synthesized compounds on DPPH oxidase protein showed a high binding affinity, confirming the experimental results recorded. The synthesized compounds deserve a consideration for further analyses regarding the control of oxidative stress and their use as possible antioxidant agents in the pharmaceutical industry.
Published online: 16th November, 2023
■ Synthesis and Properties of Novel Thiophene Polycyclic Aromatic Hydrocarbons Based on Pyrene and Their Radical Cations
Shunjie Li and Jian Chen*
*College of Chemistry and Materials Science, Huaibei Normal University, 100 Dongshan Road, Xiangshan District, Huaibei City, Anhui Province, China
Abstract
Two new thiophene-modified pyrene derivatives, 4,5,9,10-tetra- (2-(5-methyl)thienyl)-2,7-di-tert-butylpyrene (1) and 4,5,9,10-tetra- (2-(5-methoxy)thienyl)-2,7-di-tert-butylpyrene (2), were designed and synthesized via Friedel–Crafts alkylation and Stille coupling reactions of pyrene. The stable monoradical cations 1•+ and 2•+ based on the thiophene-modified pyrene derivatives were generated by the one-electron oxidation of the pyrene-based thiophene polycyclic aromatic groups with Ag[Al(ORF)4] (ORF = OC(CF3)3). Their structures and properties were investigated using 1H nuclear magnetic resonance spectroscopy, ultraviolet–visible spectrophotometry, X-ray diffraction, density functional theory calculations, and electron paramagnetic resonance spectroscopy. The electron spin density was mainly concentrated on the pyrene ring, with a minor spillover to the peripheral thienyl moieties. Compound 1•+, which is the first reported monoradical cation of thiophene-modified pyrene, is expected to have broad application prospects in the fields of semiconductors and optoelectronic materials.
Published online: 17th November, 2023
■ Diterpene Glycosides Derived from Aster Spathulifolius Have Immunomodulatory Effects
Jin Kawano, Ryosuke Fukada, Kosuke Sato, Atsuhito Kitajima, Masayuki Kirihara, Keisuke Tsuge, Mayu Kumeta, Takuya Hara, Hitoshi Hashimoto, Koji Tani,* and Takashi Kamada*
*Department of Materials and Life Science, Faculty of Science and Technology, Shizuoka Institute of Science and Technology, 2200-2 Toyosawa, Fukuroi, Shizuoka 437-8555, Japan
Abstract
Senescence-associated secretory phenotype (SASP) factors, involved in inflammation and tumorigenesis, can be inhibited by CD39, which degrades extracellular ATP. In this study, we analysed the chemical composition of the extracts of Aster spathulifolius, a coastal medicinal plant belonging to the Asteraceae family, and thereafter, isolated and determined the structures of the active components. We also treated THP-1 cells with the A. spathulifolius extracts and observed CD39 expression. Nine secondary metabolites, including a new diterpene glycoside 1, were isolated. Compounds 1 and 3–7 substantially promoted CD39 expression in THP-1 cells, and compound 3, the abundant component, showed the strongest effect in this regard, possibly degrading ATP and inhibiting the SASP.
Published online: 15th November, 2023
■ Diversity-Oriented, One Step Synthesis of Chromeno[2,3-b]Indoles and Thiochromeno[2,3-b]Indoles under Microwave-Assisted Conditions
Krisztián Biró, Camille Pinard, János Tatai, and Miklós Nyerges*
*Early Process Development, Servier, 7, Záhony utca, Hungary
Abstract
A general and efficient synthesis of tetracyclic chromeno[2,3-b]indoles, thiochromeno[2,3-b]indoles and 6H-indolo[2,3-b]quinolines has been achieved through a microwave-assisted, metal free, base catalyzed domino Knoevenagel condensation, intramolecular cyclization process starting from simple indoline-2-thiones and 2-substituted benzaldehyde derivatives. This approach provides a straightforward, atom economical and concise route to access a range of otherwise not easily available heterocycles in good yields.
Published online: 29th November, 2023
■ Evaluation of 4,4'-Diaminodiphenylmethane as A Platform for Proton, pH, and Metal Ion Responsive Fluorescent Probe
Takaaki Miyazaki,* Shunsaku Watanabe, Shoko Oka, Taiyou Tsutsumi, and Osamu Hayashida*
*Department of Chemistry, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, Japan
Abstract
4,4'-Diaminodiphenylmethane (DPM)-based fluorescent probes have been reported. We designed a new fluorescent probe 1, having bis(4-methoxyphenyl)maleimide and an amino group as a fluorophore and a sensing part, respectively, in which DPM was used as a platform for sensing molecules to utilize its advantage. The fluorescence intensity of 1 increased upon adding trifluoroacetic acid in MeCN, CH2Cl2, and toluene, indicating that 1 showed as a proton sensor. The fluorescence spectral change of 1 was observed in a mixture of MeCN and various pH buffers. Moreover, 1 behaved as a metal (zinc or nickel) ion sensor with 2-formylpyridine by forming the Schiff base skeleton. The metal ion sensing behavior of 1 could be applied to an AND circuit.
Published online: 29th November, 2023
■ Encapsulation of Cofacial Diarylacetylene Dimers Using [C2]Daisy Chain Rotaxane Strategy
Susumu Tsuda,* Kaito Kawakita, Yumeki Yano, Naoto Yasumura, Shin-ichi Fujiwara, and Yutaka Nishiyama*
*Depertment of Chemistry, Faculty of Dentistry, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan
Abstract
[c2]Daisy chain rotaxanes are mechanically interlocked molecules that can cofacially assemble two -conjugated molecules. In this study, we employed a rotaxane architecture to encapsulate diarylacetylene dimers modified with an electron-withdrawing or electron-donating substituent in two permethylated -cyclodextrins. Solvent- and concentration-dependent 1H nuclear magnetic resonance measurements indicated the selective formation of the cofacial dimers. These dimers were mechanically interlocked by condensation with 4-{2-[2-(2-hydroxyethoxy)ethoxy]ethoxy}-3,5-dimethylaniline to obtain the corresponding [c2]daisy chain rotaxanes (up to 68% yield). UV-visible absorption and fluorescence spectra revealed that the diarylacetylene substituents modulated the optical properties of the rotaxanes.
Published online: 24th November, 2023
■ Chemical Structures and Cytotoxic Activities of the Constituents Isolated from Citrus Sphaerocarpa
Takuya Muraoka, Daisuke Imahori,* Rina Miyagi, Tomoe Ohta, Tatsusada Yoshida, and Hiroyuki Tanaka*
*Pharmacognosy, Faculty of Pharmaceutical Sciences, Sanyo-onoda City University, 1-1-1 daigaku-dori, Sanyo-Onoda, Yamaguchi, Japan
Abstract
From the peels of Citrus sphaerocarpa, two new limonoids, sphaerocarpain Ⅰ and Ⅱ were isolated together with five known compounds including methyl deacetylnomilinate and ichangin. The chemical structures of the new compounds were elucidated based on chemical/physicochemical evidence. For sphaerocarpain Ⅰ and Ⅱ, the absolute configuration was established by comparison of experimental and predicted electronic circular dichroism (ECD) data. Among the isolated compounds, sphaerocarpain I, II, methyl deacetylnomilinate and ichangin showed cytotoxic activity against both human neuroblastoma cells (SH-SY5Y) and human glioblastoma cells (U-251 MG).