

HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
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Most Cited Articles
The most cited articles are updated on a monthly basis and available as Last 3 Years. Citation data is obtained through CrossRef's Cited-Linking service.
Note: The Top 20 Citations are published across all volumes.
Published online: 1 January, 1970
■ Recent Progress in the Chemistry of Polyacylated Anthocyanins as Flower Color Pigments
Toshio Honda* and Norio Saito
*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
It is recognized that the bluing effect and stabilization of flower colors will remarkably depend on the number of aromatic acids presented in the polyacylated anthocyanins. Although polyacyl functions would be considered to contribute strongly in the bluing of the flower color at the early stage of the investigation of polyacylated anthocyanin chemistry, the stabilization of flower color is considered to be another important objective by the presence of these aromatic acids at the present time. Since aromatic acids in the polyacylated anthocyanins are obviously linked with the sugar residues through the ester bonds, the polyacylated anthocyanins are classified into seven types by the substitution pattern of acyl functions, and the effect of the stacking structures of polyacyl anthocyanins on the stabilization of the flower color depending on the substitution pattern of acyl groups will be discussed. The physicochemical properties (NMR, UV-VIS spectra) in relation to the stability of the anthocyanins will also be discussed.
Published online: 1 January, 1970
■ Recent Developments of Free-Radical Substitutions of Heteroaromatic Bases
Francesco Minisci,* Elena Vismara, and Francesca Fontana
*Dipartimento di Chimica, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy
Abstract
The most recent mechanistic and synthetic aspects of the substitution of protonated heteroaromatic bases by nucleophilic carbon-centered radicals are reviewed. From mechanistic point of view the following aspects are discussed; i ) Structurereactivity relationship; i i ) Rearomatization of the radical adducts; iii) Solvent and isotope effects; iv) Overlap area with ionic reactions. The synthetic developments concern the following topics: i) Selectivity with carbonyl radicals; ii) Alkyl iodides as sources of alkyl radicals; iii) Alkylation by carboxylic acids; iv) Vinylation by olefins; v) Oxyalkylation by ethers; vi) Catalytic processes; vii) Substitution with strongly nucleophilic radicals.
Published online: 1 January, 1970
■ Cyclic Carboxylic Imide Structures as Structure Elements of High Stability. Novel Developments in Perylene Dye Chemistry
Heinz Langhals
*Institut für Organische Chemie, Universität München, Karlstrasse 23, D-80333 München, Germany
Abstract
Cyclic carboxylic imides are structure elements in aromatic heterocycles with high persistency. Their attachment to perylene leads to the perylene dyes; the synthesis and unique properties of the dyes are reported and discussed. An extension of the principle to other aromatics is made.
Published online: 15 June, 2007
■ From Haloquinolines and Halopyridines to Quinoline- and Pyridinesulfonyl Chlorides and Sulfonamides
Andrzej Maslankiewicz,* Krzysztof Marciniec, Maciej Pawlowski, and Pawel Zajdel
*Department of Organic Chemistry, The Medical University of Silesia
Jagiellonska 4, 41-200 Sosnowiec, Poland
Abstract
The action of sodium methanethiolate (in boiling DMF) towards haloazines (i.e. chloro- or bromo-pyridines and quinolines) (1) (with halogen substituent in non-aza-activated position) causes sequentially halogen ipso-substitution to methylthioazines (2) and then S-demethylation to azinethiolates (3A), which were: i) subjected to S-methylation, ii) oxidized to diazinyl disulfides (4) and iii) oxidatively chlorinated to azinesulfonyl chlorides (5). α- and β-pyridine- and quinolinesulfonyl chlorides (5a, 5c, 5d and 5f) were prepared by oxidative chlorination of respective disulfides (4) performed in conc. hydrochloric acid and characterized by 1H and 13C NMR spectra. All azinesulfonyl chlorides (5) were effectively converted to corresponding azinesulfonamides (6).
Published online: 1 January, 1970
■ LI-F Antibiotics, a Family of Antifungal Cyclic Depsipeptides Produced by Bacillus polymyxa L-1129
Jun Kuroda, Toshio Fukai, Masataka Konishi, Jun Uno, Keiji Kurusu, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Twelve antifungal depsipeptide antibiotics named as LI-F03a, LI-F03b, LI-F04a, LI-F04b, LI-F05a, LI-F05b, LI-F06a, LI-F06b, LI-F07a, LI-F07b, LI-F08a and LI-F08b have been isolated from the fermentation broth of Bacillus polymyxa L-1129 by use of extensive preparative HPLC. Not only their intrinsic antifungal and anti-Gram positive bacterial activity, they also showed unique synergistic antifungal effect in combination with the azole group antifungal agents. The structural studies disclosed that they are cyclic depsipeptides composed of six amino acids (three of them, L-threonine, D-allo-threonine and D-alanine being in common among all components and other three amino acids variable) on which is substituted by a 15-guanidino-3-hydroxypentadecanoic acid.
Published online: 28 October, 2008
■ New [11C]Phosgene Based Synthesis of [11C]Pyrimidines for Positron Emission Tomography
Koh-ichi Seki,* Ken-ichi Nishijima, Kimihito Sanoki, Yuji Kuge, Masayuki Takahashi, Hiromichi Akizawa, Nagara Tamaki, Leonard I. Wiebe, and Kazue Ohkura*
*Central Institute of Radio Isotope Science, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan
Abstract
Thymine, 5-FU, and uracil were successfully synthesized through a procedure involving a cyclocondensation of triphosgene with newly developed α-substituted β-aminoacrylamides intermediates (1a, X = Me; 1b, X = F; 1c, X = H). The radioligands [2-11C]thymine and [2-11C]5-fluorouracil were synthesized in high radiochemical yields in 16-17 minutes from the end of bombardment by applying the cyclocondensation method with [11C]COCl2.
Published online: 8 July, 2010
■ Synthesis and Anti-HIV Activity of New 3’-O-Phosphonomethyl Nucleosides
Michal Cesnek and Piet Herdewijn*
*K.U. Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium
Abstract
The synthesis of 4’(S)-ethynyl-2’-deoxythreosyl and β-D-galactofuranose nucleosides starting from D-galactose is described. The nucleobase is introduced using Vorbruggen glycosylation. The 4’(S)-ethynyl derivatives are obtained by selective oxidation of vicinal diol to the aldehyde and subsequent Bestmann modification of Seyferth-Gilbert homologation. All compounds were evaluated for activity against HIV (MT4 cells), RSV (Hep2 cells) and HCV (HCV replicon cells), however, none of these compounds demonstrate biological activity.
Published online: 1 January, 1970
■ Synthesis and Biological Evaluation of Water Soluble Taxoids Bearing Sugar Moieties
Tadakatsu Mandai,* Hiroshi Okumoto, Tetsuta Oshitari, Katsuyoshi Nakanishi, Katsuhiko Mikuni, Ko-ji Hara, Ko-zo Hara, Wakao Iwatani, Tetsuya Amano, Kosho Nakamura, and Yoshinori Tsuchiya
*Department of Chemical Technology, Kurashiki University of Science & the Arts, 2640 Nishinoura, Tsurajima-cho, Kurashiki 712-8505, Japan
Abstract
Synthesis and biological evaluation of a variety of water soluble taxoids with sugar moieties are described.
Published online: 13 December, 2013
■ Solvent-Free Synthesis of New Chiral 3-Phenylamino-3,5-dihydro-4H-imidazol-4-one Derivatives from α-Amino Acid Phenylhydrazides
Yakdhane Kacem and Béchir Ben Hassine*
*Department of Chemistry, Faculty of Sciences, Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, Avenue of the Environment, 5019 Monastir, Tunisia
Abstract
Enantiopure 2,5-disubstituted 3-phenylamino-3,5-dihydro-4H-imidazol-4-one derivatives were obtained in good to excellent yields by condensation of chiral α-amino acid phenylhydrazides and triethyl orthoesters in the presence of dry acetic acid as catalyst. All reactions are performed under solvent-free and mild conditions.
Published online: 1 January, 1970
■ Kinetic Resolution of 2-Furylcarbinols Using the Sharpless Oxidation and Its Application to the Synthesis of (5R,6S)-6-Acetoxy-5-hexadecanolide
Tetsuji Kametani,* Masayoshi Tsubuki, Yoko Tatsuzaki, and Toshio Honda
*Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
Kinetic resolution of 2-furylcarbinols employing 10 mol % of Ti(0iPr)4 in the presence of molecular sieves 3A under the Sharpless oxidation condition generally affords corresponding optically actlve 2-furylcarbinols in a range of 80-98% ee. Application of the optically active 1f to the synthesis of (5R,6S)-6-acetoxy-5-hexadecanolide (8), the major component of the oviposition attractant pheromone of the mosquito Culex pipens fatigans, has also been achieved.
Published online: 28 April, 2021
■ Recent Achievements in the Synthesis of Heterocyclic Compounds by Phthalhydrazide-Based Multicomponent Reactions
Ghodsi Mohammadi Ziarani,* Negar Jamasbi, and Fatemeh Mohajer
*Department of Chemistry, Faculty of Physic and Chemistry, Alzahra University, Tehran, Iran. P. O. Box 1993893973
Abstract
Phthalhydrazide is one of the useful starting material toward the synthesis of heterocyclic compounds, and considered as a valuable structural unit in organic synthesis due to its significant pharmacological and biological activities. There are many multicomponent reactions using phthalhydrazide under different conditions. This review article aims to give an overview of recent applications of phthalhydrazide in the multicomponent reactions during the period of 2006 to 2021.
Published online: 27 January, 2015
■ Synthesis of Triazole, Indole, and Five or Six-Membered Saturated Heterocyclic Compounds
Yasunari Monguchi,* Yoshinari Sawama, and Hironao Sajiki*
*Laboratory of Organic Chemistry, Department of Pharmaceutical Sciences, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu 501-1196, Japan
Abstract
Heterogeneously-catalyzed synthetic methods for the preparation of 1,2,3-triazoles, indolines, indoles, and saturated heterocyclic compounds, such as piperidine and pyrrolidine, are demonstrated. Triazoles are intermolecularly synthesized by the 1,3-dipolar cycloaddition of alkynes with azides using heterogeneous copper catalysts. Solvent-free triazole syntheses are also described. Inter- and intramolecular annulations as indole syntheses are summarized; e.g., a palladium on carbon (Pd/C)-catalyzed Yamanaka–Larock method affords 2- or 2,3-substituted indoles from 2-iodoaniline derivatives and mono- or di-substituted alkynes; an intramolecular Pd/C-catalyzed Buchwald–Hartwig reaction of 2-bromophenethylamine derivatives temperature-dependently affords indolines or indoles. Pd/C can also catalyze an intermolecular aromatic amination of bromoarenes with indoles to generate the corresponding N-arylindoles. The application of the hydrogenation technology using 10% Pd/C, 10% rhodium on carbon (Rh/C), or 10% ruthenium on carbon (Ru/C) as a catalyst is finally introduced for the synthesis of indole by the intramolecular hydrogenative N-alkylation of 2-cyanomethylaniline and piperidine, pyrrolidine, and tetrahydrofuran derivatives by the arene hydrogenation of pyrridine, pyrrole, and furan derivatives under relatively mild conditions, respectively.
Published online: 1 January, 1970
■ The Crystal and Molecular Structure of 2,3,5,6-Tetraphenyl-1,4-dithiin
Ian W. Jones and Patrick E. Hoggard*
*Department of Chemistry, Santa Clara University, 500 El Camino Real, Santa Clara, California 95053-270, U.S.A.
Abstract
The phenyl rings in 2,3,5,6-tetraphenyl-1,4-dithiin have neither of the two most obvious configurations: all perpendicular to the dithiin ring (paddlewheel), or parallel to the dithiin double bonds (butterfly). Instead, there are two phenyls in each orientation.
Published online: 30 May, 2013
■ ent-3,4-seco-Labdane Diterpenoids from Callicarpa nudiflora Leaves with Anti-inflammatory Activity
Lei Zhang, Jian Huang, Mingsheng Liu,* Cui Zhang, Guoyu Li, Ke Zhang, Lin Dong, and Jinhui Wang*
*School of Traditional Chinese Materia Medicine, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang, China
Abstract
Two new ent-3,4-seco-labdane diterpenoids, ent-3,4-seco-16-hydroxy-12,15-epoxy-4(18),8(17),12,14-labdatetraen-3-oic acid (1) and ent-3,4-seco-12R,15-epoxy-4(18),8(17),13-labdatrien-3-oic acid (2), were isolated from the leaves of Callicarpa nudiflora. Their structures were elucidated by extensive spectroscopic analysis and the biosynthetic pathways leading to these compounds were proposed. The two compounds both exerted potent inhibitory activity against the production of nitric oxide (NO) in RAW264.7 stimulated by lipopolysaccharide (LPS).
Published online: 21 November, 2008
■ Facile Syntheses of Three Ahp-Type Building Blocks with Complementary Reactivity
Wen Chen, Xiao Zheng, Yuan-Ping Ruan, and Pei-Qiang Huang*
*Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, China
Abstract
Two protected 3-amino-6-hydroxy-2-piperidone derivatives (Ahp, 12 and 6), as well as a thioether analogue (7) were synthesized starting from L-glutamic acid in four, five, and six steps respectively. The Ahp derivatives 12 and 6 are not only the structural feature found in many naturally occurring bioactive depsipeptides, but also precursors of the N-acyliminium such as D; while the (S)-thioether 7 was shown to be an effective synthetic equivalent of the novel 2-piperidone N-α-carbanion E via the lithium-naphthalenide (LN)-mediated reductive lithiation, capable of reacting with carbonyl compounds without an acidic α–position to give the α-hydroxyalkylation products.
Published online: 22 December, 2011
■ Hydrolysable Tannins Isolated from Syzygium aromaticum: Structure of a New C-Glucosidic Ellagitannin and Spectral Features of Tannins with a Tergalloyl Group
Li-Ming Bao, _ Eerdunbayaer, Akiko Nozaki, Eizo Takahashi, Keinosuke Okamoto, Hideyuki Ito, and Tsutomu Hatano*
*Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
Eighteen hydrolysable tannins, including a new C-glucosidic tannin named aromatinin A (1), were isolated from an aqueous acetone extract of dried flower buds of Syzygium aromaticum Merr. et Perry. We determined that 1 had a gallic acid C-glucoside structure, based on the spectral data and synthesis from casuarinin (18) and gallic acid (20). This is a rare example of hydrolysable tannins with gallic acid C-glucoside structure. We also report the 1H nuclear magnetic resonance (NMR) spectral features of syzyginin A (2), bicornin (3), and platycaryanin A (4), which were also isolated from S. aromaticum, based on their structures with a tergalloyl group or its depsidone form. The remaining known compounds were identified as alunusnin A (5), rugosin C (6), 1,2,3-tri-O-galloyl-β-D-glucose (7), 1,2,3,6-tetra-O-galloyl-β-D-glucose (8), tellimagrandin II (9), casuarictin (10), heterophylliin D (11), rugosin D (12), rugosin F (13), euprostin A (14), 1,2-di-O-galloyl-3-O-digalloyl-4,6-O-(S)-hexa- hydroxydiphenoy-β-D-glucose (15), alienanin B (16), squarrosanin A (17), and 18. The antifungal effects of hydrolysable tannins, 9, 12, and 18 against Candida strains are also described.
Published online: 14 December, 2018
■ Synthesis, Conformation, and Biological Activities of a Des-A-Ring Analog of 18-Deoxy-Aplog-1, a Simplified Analog of Debromoaplysiatoxin
Yoshiki Ashida, Ryo C. Yanagita,* Yasuhiro Kawanami, Mutsumi Okamura, Shingo Dan, and Kazuhiro Irie
*Department of Applied Biological Science, Faculty of Agriculture, Kagawa University, 2393 Ikenobe, Miki, Kagawa 761-0795, Japan
Abstract
10-Me-Aplog-1 as a simplified analog of tumor-promoting debromoaplysiatoxin and a potent activator of protein kinase C (PKC) is a promising chemotherapeutic agent. In this study, we synthesized a des-A-ring analog (4) of 18-deoxy-aplog-1 as a synthetically-accessible analog. Compound 4 retained the conformation of the PKC-recognition part of aplogs. Moderate affinity for conventional PKC isozymes (α, β, γ) and anti-proliferative activity against NCI-H460 (lung) and MKN45 (stomach) human cancer cell lines were observed. The results suggest that 4 could serve as a lead compound for the development of conventional PKC isozyme-selective chemotherapeutic agents.
Published online: 2 July, 2021
■ New and Practical Synthesis of GS-441524, the Key Intermediate of Remdesivir
Bo Li, Han Wang,* Cong Sun, Sheng Lu, LinLin Kang, and Shun Jiang
*College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China
Abstract
A new and practical synthesis of GS-441524, the key intermediate for remdesivir, is developed. 4-Amino-7-iodopyrrolo[2,1-f][1,2,4]triazine is protected by DMF-DMA, and reacted with 2,3,5-tri-O-benzyl-D-ribonolactone to give the product in 61% isolated yield. The next cyanation and debenzylation are carried out at −30 °C successively in 67% yield over two steps with >99% purity (HPLC). Purification methods of the intermediates and the final product involved in the route are developed.
Published online: 29 May, 2017
■ Catalytic Enantioselective Desymmetrization of meso-Aziridines with Fluoromalonates
Seiya Fukagawa, Yingjie Xu, Masahiro Anada, Tatsuhiko Yoshino, and Shigeki Matsunaga*
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
Catalytic enantioselective desymmetrization of meso-aziridines with fluoromalonates is described. Optimization studies revealed that the appropriate combination of Brønsted basic metal and Lewis acidic metal is important for promoting the reaction using fluoromalonates. A heterodinuclear Gd(OiPr)3/Y(OTf)3/Schiff base = 1:1:1 was the best catalyst, and ring-opening adducts, synthetic precursors for α-fluoro-γ-amino acids, were obtained in 98%~17% yield and >99.5%~99% ee. Transformation of the ring-opening adduct into α-fluoro-γ-lactam was also demonstrated.
Published online: 10 February, 2003
■ Improved Oxidation of Active Methyl Group of N-Heteroaromatic Compounds by Selenium Dioxide in the Presence of tert-Butyl Hydroperoxide
Yoshinobu Tagawa, Katsuya Yamashita, Yoshitaka Higuchi, and Yoshinobu Goto*
*Faculty of Pharmaceutical Sciences, Fukuoka University, Nakamura, Jonan-ku, Fukuoka, 814-0180, Japan
Abstract
The oxidation of active methyl group of N-heteroaromatic compounds including both of bicyclic and monocyclic compounds using SeO2 was considerably improved in the presence of tert-butyl hydroperoxde in dioxane to give the corresponding aldehyde or carboxylic acid in the moderate to good yields. The present oxidation proceeds more mildly and more selectively to form aldehyde rather than carboxylic acid, compared with conventional SeO2 oxidation without tert-butyl hydroperoxide.