HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Masakatsu Shibasaki's Special Issues, Vol. 95, No. 1, 2017
Published online: 7th October, 2016
■ Synthesis of the 5-Methyluridine Monomer of 3’-O,4’-C-Ethyleneoxy-Bridged Nucleic Acid
Takashi Osawa, Masakazu Dohi, Yuka Hitomi, Yuta Ito, Satoshi Obika,* and Yoshiyuki Hari*
*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
Abstract
A novel bridged nucleic acid, 3ʹ-O,4ʹ-C-ethyleneoxy-bridged nucleic acid (3ʹ,4ʹ-EoNA), forming 2ʹ,5ʹ-linkage with the flanking nucleotides in oligonucleotides was designed. The 3ʹ,4ʹ-EoNA is expected to improve the biophysical properties of the oligonucleotides (e.g., binding affinity with complementary single-stranded oligonucleotides and resistance against nuclease digestion) because of the presence of the 6ʹ-oxygen atom. In this study, the synthesis of the 5-methyluridine monomer of 3ʹ,4ʹ-EoNA was achieved via Lewis acid-mediated C4ʹ-iodoethoxylation followed by intramolecular 1,4-dioxane ring formation. Here, we describe, in detail, the results of the study.
Published online: 11th November, 2016
■ Synthesis and Electrochemical Properties of Azulene-Substituted Tetracyanobutadiene and Dicyanoquinodimethane Chromophores Connected with Naphthalene Cores
Taku Shoji,* Mitsuhisa Maruyama, Akifumi Maruyama, Daichi Nagai, Miwa Tanaka, Ryuta Sekiguchi, Shunji Ito, and Tetsuo Okujima
*Department of Chemistry, Faculty of Science, Shinshu University, Asahi 3-1-1, Matsumoto, Nagano 390-8621, Japan
Abstract
Azulene-substituted tetracyanobutadienes (AzTCBDs) and dicyanoquinodimethanes (AzDCNQs) connected with naphthalene cores were prepared by the reaction of 1-azulenylalkynes with tetracyanoethylene (TCNE) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) in a formal [2 + 2] cycloaddition–retroelectrocyclization. The characteristic intramolecular charge transfer (ICT) characters were investigated by using UV/Vis spectroscopy and theoretical calculation. The redox behaviors of AzTCBDs and AzDCNQs were examined by cyclic voltammetry and differential pulse voltammetry, which revealed their properties of multi-electron transfer depending on the number of AzTCBD and AzDCNQ moieties. Moreover, significant color changes were observed by visible spectroscopy under the electrochemical reduction conditions.
Published online: 31st October, 2016
■ Preparation of (R)-3-Hydroxy-N-methylpiperidine, a Synthetic Key Intermediate of (R)-Mepenzolate, Based on the Lipase-Catalyzed Resolution of the Racemic Form
Yasunobu Yamashita, Kengo Hanaya, Mitsuru Shoji, and Takeshi Sugai*
*Department of Pharmaceutical Science, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan
Abstract
In this study, a two-step method for the gram-scale synthesis of (R)-3-hydroxy-N-methylpiperidine in 97.8% enantiomeric excess (ee) is reported. The key chiral synthetic intermediate of (R)-mepenzolate was formed in 22% yield over two steps using a commercially available and inexpensive racemic alcohol as the starting material. In the first step, Candida antarctica lipase B-catalyzed kinetic resolution of the racemic alcohol under acetylation conditions was performed to obtain the acetate form of the (R)-enantiomer in 82.1% ee (E 18). The second step involved enantio-enrichment using the same lipase to catalyze deacetylation. The ee of the product (R)-alcohol was further enriched to 97.8%.
Published online: 22nd December, 2016
■ π-Expanded Cyclic Oligothiophene 12-Mers as Semishape-Persistent Macrocycles
Mika Imamura, Hideyuki Shimizu, Jun Yamakawa, Hiroyuki Otani, Tohru Nishinaga, and Masahiko Iyoda*
*Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan
Abstract
π-Expanded macrocyclic oligothiophene 12-mer E,E-12T10A, 18-mer E,E,E-18T15A, and 24-mer E,E,E,E-24T20A composed of thienylene, ethynylene, and vinylene moieties were synthesized in good total yield by the McMurry coupling reaction of dialdehyde 1. E,E-12T10A was converted to cyclo[12](3,4-dibutyl-2,5-thienylene-ethynylene) 12T12A in 20% yield by bromination-dehydrobromination procedure. Furthermore, the synthesis of 12T12A was carried out by using double elimination procedure starting from the sulfone dianion 22- and dialdehyde 1. The crystal structure of E,E-12T10A was determined by X-ray analysis. In the solid state, macrocyclic oligothiophenes formed nanostructured polymorphs such as single crystals, petal-shaped structure, and chained lumps depending on the ring size.
Published online: 19th December, 2016
■ Efficient Total Syntheses of Natural Neopterin Glycosides: Neopterin Glucronide and Solfapterin
Tadashi Hanaya,* Katsuya Iwasaki, Kaori Saeki, and Takafumi Hattori
*Department of Chemistry, Faculty of Science, Okayama University, Tsushima-naka, Okayama 700-8530, Japan
Abstract
1’,2’-Di-O-acetyl-N2-(N,N-dimethylaminomethylene)-3-[2-(4-nitro- phenyl)ethyl]neopterin (11a) and its 1’,2’-di-O-benzoyl analog (11b) were prepared from neopterin in 5 steps, respectively. Glycosylation of 11a with methyl 2,3,4-tri-O-benzoyl-α-D-glucopyranosyluronate bromide (15b) in the presence of silver triflate afforded the corresponding 3’-O-(β-D-gluco- pyranosyl)neopterin derivative (18) in 64% yield. The similar treatment of 11b with 2-azido-3,4,6-tri-O-benzoyl-2-deoxy-α-D-glucopyranosyl bromide (21b) provided the corresponding 3’-O-(α-D-glucopyranosyl)neopterin derivative (23a) in 58% yield. The first syntheses of neopterin glucronide (5) and solfapterin (6) were achieved by successive removal of the protecting groups of 18 and 23a, respectively.
Published online: 19th December, 2016
■ Syntheses of 2-Vinyl-2,3-dihydropyrroles and 3-Methylene-1,2,3,4-tetrahydropyridines by Palladium-Catalyzed Cyclization of N-Tosyl Imines with Allylic Diesters
Masahiro Yoshida,* Kouki Kinoshita, and Kosuke Namba
*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima, 770-8514, Japan
Abstract
A palladium-catalyzed cyclization of N-tosyl imines with allylic diesters is described. The reactions of N-tosyl imines with 2-buten-1,4-diol dicarbonate and 2-methylene-1,3-propanediol diacetate afforded 2-vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines, respectively.
Published online: 31st October, 2016
■ Concise Formation of Spirocyclic Compounds for Marine Phycotoxins
Jun Ishihara,* Shingo Tojo, Takuya Makino, Hiroshi Sekiya, Akiko Tanabe, Mitsutaka Shiraishi, Akio Murai, and Susumi Hatakeyama*
*Graduate School of Biomedical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
The stereoselective construction of azaspiro[5.6]dodecenone skeletons by the chiral BOX/copper-mediated Diels-Alder reaction is described. The cycloaddition reaction of α-methylene caprolactams and functionalized dienes allows the concise formation of spirocyclic structures of marine phycotoxins, such as pinnatoxin and spirolide.
Published online: 17th February, 2017
■ 8-Methyl Derivatives of Aristeromycin, Neplanocin, 3-Deazaneplanocin and Related Analogs
Xueqiang Yin, Qi Chen, Wei Ye, Chong Li, and Stewart W. Schneller*
*Molette Laboratory for Drug Discovery, Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849-5312, U.S.A.
Abstract
The promising biological properties of 8-methyladenosine prompted a study of the related carbocyclic analogs based on aristeromycin and neplanocin. These target compounds have been prepared from strategically protected parent carbocyclic nucleoside derivatives or built up from suitable cyclopentanols and cyclopentenols. Several of these nucleosides were evaluated against a variety of RNA and DNA viruses to determine the potential of the 8-methyl series as a source for new antiviral agents. Encouraging results towards Epstein-Barr virus, cowpox, vaccinia virus, Ebola, and the flaviviruses (dengue and yellow fever) suggests more extensive studies.
Published online: 7th December, 2016
■ Synthesis of Photophore and Fluorophore Modified O-Benzylserine Derivatives
Makoto Hashimoto,* Takuma Yoshida, Zetryana Puteri Tachrim, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, and Yuichi Kanaoka
*Graduate School of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan
Abstract
O-Benzylation of serine is one of the important protection methods for solid phase peptide synthesis. The utilities of the protection group may be indicated that chemical modifications for O-benzylserine will be utilized to make functional peptides on solid phase synthesis. Detailed studies for effective synthesis of photoreactive and fluorophore containing O-benzylserine derivatives without racemization were reported.
Published online: 20th January, 2017
■ A Direct Synthesis of 2,2-Disubstituted 3-Silylchromenes by [4+2] Cycloaddition of in situ Generated o-Quinonemethides with Electron-Rich Alkynes
Kenta Tanaka, Yujiro Hoshino, and Kiyoshi Honda*
*Graduate School of Environment and Infomation Science, Yokohama National University, Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan
Abstract
A direct synthesis of 2,2-disubstituted 3-silylchromenes by [4+2] cycloaddition of in situ generated o-quinonemethides with electron-rich alkynes has been developed. The procedure is applicable for easily available starting materials like various substituted alkynylsilanes and salicylaldehydes. The present reaction provides versatile access to functionalized 2H-chromenes that would be a useful tool for the synthesis of biologically and photochemically active molecules.
Published online: 19th December, 2016
■ Synthesis of Tricyclic Dioxetanes That Exhibit Intramolecular Charge-Transfer-Induced Decomposition: Relationship between Structure and Chemiluminescence Efficiency
Nobuko Watanabe,* Yuukou Mizuno, Yoshinori Maeda, Hisako K. Ijuin, and Masakatsu Matsumoto*
*Department of Chemistry, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan
Abstract
Tricyclic dioxetanes bearing a 3-oxyphenyl group 3–5 were stereoselectively synthesized in high yields by the singlet oxygenation of three types of 5-(3-oxyphenyl)-2,3-dihydrofurans fused with a cyclopentane ring 6b–8b. Upon treatment with tetrabutylammonium fluoride (TBAF) in DMSO or acetonitrile at 25 °C, these dioxetanes underwent charge-transfer-induced decomposition (CTID) accompanied by the emission of bright blue light. Although all of these dioxetanes gave excited oxyanions of 3-hydroxybenzoate as an emitter, their chemiluminescence efficiencies were significantly different and depended on their structures.
Published online: 22nd June, 2016
■ Synthesis of (±)-Cephalanthrin A Using Baeyer-Villiger Oxidation
Tomoki Itoh, Takumi Abe, Tominari Choshi, Takashi Nishiyama, and Minoru Ishikura*
*School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
Indoloquinazoline alkaloid (±)-cephalanthrin A was synthesized through the Baeyer-Villiger oxidation of the phenyl ketone derived from aldol reaction of tryptanthrin and acetophenone.
Published online: 13th July, 2016
■ Preparation and Biological Activity of Novel Twin-Drug Type C2-Symmetrical Cyclic Phenylboronic Acid Derivatives
Makoto Furutachi, Ayumi Ejima, Reika Tsuru, Saho Goto, Toshiaki Gondo, Kenta Ako, Saho Fuchigami, Saya Fujii, Arisa Okumura, Ayumi Tozuka, Kazumi Yokomizo, Jian-Rong Zhou, Hiroshi Inao, Yutaro Ono, Nobuhiro Kashige, Fumio Miake, and Kunihiro Sumoto*
*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Abstract
We here report the results of evaluation of antibacterial and anti-herpes simplex virus-1 (HSV-1) activities of a novel twin-drug type C2-symmetrical boronic acid and its pinacol ester derivatives. By using a primitive amide bond formation reaction, various targeted C2-symmetrical cyclic phenylboronic acid derivatives were obtained from the reactions of commercially available amino-substituted phenylboronic acid derivatives and diacid dichlorides. The C2-symmetrical bivalent molecule 3bd containing two cyclic phenylboronic acid pinacol ester moieties and a flexible hexamethylene linker showed both antibacterial activity (S. aureus) and anti-HSV-1 activity. The corresponding boronic acid derivative 3dd showed neither antibacterial nor anti-HSV-1 activity, indicating the importance of two pinacol ester functionalities.
Published online: 5th August, 2016
■ Synthesis of γ-Trifluoromethyl Tetronate Derivatives from Squarates
Yoshihiko Yamamoto,* Yosuke Takamizu, Takashi Kurohara, and Masatoshi Shibuya
*Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
Abstract
Squarates and semisquarates were treated with TMSCF3 in the presence of a catalytic amount of AcONa in DMF at room temperature to afford 4-trifluoromethyl-4-hydroxycyclobutenones. Subsequent oxidative ring expansion of these products was performed using Pb(OAc)4 in the presence of MS 4A in 1,2-dichloroethane at 50 °C to afford γ-trifluoromethyl tetronate derivatives.
Published online: 31st October, 2016
■ Two New Galloyl Glucosides from the Bark of Castanopsis fargesiI
Yong Lin Huang,* Ya-Feng Wang, Jin-Lei Liu, Rui-jie He, Xiao-Jie Yan, Lei Wang, and Dian-Peng Li
*Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, NO. 85 Yanshan Street, Guilin, Guangxi 541006, China
Abstract
In a continuing phytochemical investigation of the Castanopsis species (Fagaceae), two new galloyl glucosides, 5-O-β-D-(6'-O-galloyl)glucopyranosyl pyran-2-one (1) and 4-hydroxymethyl-2-methoxyphenol 1-O-β-D-(6'-O-galloyl)glucoside (2), were isolated from the ethanolic extract of the bark of Castanopsis fargesii, together with six known compounds. Their structures were elucidated on the basis of spectroscopic data analysis. The oxygen radical absorbance capacity (ORAC) values of the all compounds were measured and the known compound 4-hydroxy-2-methoxyphenol 1-O-β-D-(6'-O-galloyl)glucoside (3) showed the strongest antioxidant activity.
Published online: 19th October, 2016
■ Design and Synthesis of 1,3,5-Triazine Derivatives as Novel Inverse Agonists of Nuclear Retinoic Acid Receptor-Related Orphan Receptor-γ
Kazuma Kaitoh, Hirozumi Toyama, Yuichi Hashimoto, and Shinya Fujii*
*Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Abstract
1,3,5-Triazine structure is a versatile chemical species for development of functional molecules, including biologically active compounds. We report herein the design, synthesis and biological evaluation of novel inverse agonists of nuclear retinoic acid receptor-related orphan receptor-γ (RORγ), in which the 2-anilino-1,3,5-triazine moiety was used as a scaffold for structural development. Among the synthesized compounds, 13b exhibited potent and selective inverse agonistic activity toward RORγ, being more potent than the lead compound T0901317 (7). The results suggest that the 2-anilino-1,3,5-triazine moiety is a useful scaffold for development of inhibitory ligands of nuclear receptors.
Published online: 18th October, 2016
■ Synthesis of β-Dihydropyrrolyl and β-Pyrrolyl Acrylates and Their Antiproliferative Activity against HCT-116 and HL-60 Cells
Noriyuki Hatae,* Yoko Sakai, Kohei Yorozu, Chiaki Okada, Mitsuhiro Yoshimatsu, and Teruki Yoshimura*
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
The α,β-unsaturated carbonyl derivatives have been reported as bioactive substances, in particular acting as antiproliferative and antifungal agents. In this study, β-dihydropyrrolyl and β-pyrrolyl acrylates were synthesized by copper-mediated 5-endo cyclization of isolable Blaise-type β-enamino esters and were assessed for antiproliferative activity against HCT-116 and HL-60 cells. Some β-dihydropyrroles and β-pyrroles showed such activities, which were found to be due to different mechanisms: the β-dihydropyrroles act as cytotoxic agents, whereas the β-pyrroles act as cell cycle inhibitors.
Published online: 20th September, 2016
■ Palladium-Catalyzed Cross-Coupling of Aryl Chlorides with Arylsilatranes
Yutaro Yamamoto, Alexandre Baralle, Anaïs Godefroy, Kei Murakami, Hideki Yorimitsu,* and Atsuhiro Osuka
*Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Abstract
The cross-coupling reactions of arylsilatranes with readily available and inexpensive aryl chlorides were carried out in toluene/THF at 100 ºC for 3 h in the presence of tetrabutylammonium fluoride as an activator for smooth transmetalation and catalytic amounts of palladium(II) acetate and XPhos.
Published online: 31st January, 2017
■ Effective Separation of Am(III) from Cm(III) Using Modified BTPhen Ligands
Ashfaq Afsar, Alyn C. Edwards, Andreas Geist, Laurence M. Harwood,* Michael J. Hudson, James Westwood, and Roger C. Whitehead
*School of Chemistry, University of Reading, Whiteknights, Reading, Berkshire RG6 6AD, UK
Abstract
Electronic modulation of CyMe4-BTPhen with 5-bromo and 5-(4-hydroxyphenyl) substituents leads to enhanced separation of Am(III) from Cm(III) over 0.1 – 3 M HNO3 (SFAm/Cm = ca. 9 at 0.1 M HNO3). In addition, substituting bromine atoms at the 5 and 6 positions of the phenanthroline backbone provides a mean of separating Am(III) from Eu(III) (SFAm/Eu = ca. 240 at 3 M HNO3).
Published online: 16th September, 2016
■ Synthesis of 4-Substituted-Pyridine-2,6-dicarboxylic Acid Derivatives from Pyruvates and Aldehydes in One Pot
Pandurang V. Chouthaiwale, Sébastien Lapointe, and Fujie Tanaka*
*Chemistry and Chemical Bioengineering Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495, Japan
Abstract
4-Substituted-pyridine-2,6-dicarboxylic acid derivatives were synthesized in one pot under mild conditions via the formation of dihydropyran derivatives from pyruvates and aldehydes catalyzed by pyrrolidine-acetic acid, followed by the reaction with ammonium acetate.
Published online: 15th December, 2016
■ Structural Development Studies of Pyrazoloketone-Derived Acetyl-CoA Carboxylase Inhibitors
Shogo Okazaki, Taki Sakai, Minoru Ishikawa, Yuichi Hashimoto, and Takao Yamaguchi*
*Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Abstract
Acetyl-CoA carboxylase (ACC) plays a key role in fatty acid homeostasis in humans, and inhibitors of ACC are expected to inhibit fatty acid biosynthesis and to activate fatty acid β-oxidation. Therefore, they are considered to be candidates for treatment of metabolic syndrome and related diseases. In this context, an upstream kinase of ACC, adenosine monophosphate-activated protein kinase (AMPK), has also recently emerged as a potential therapeutic target, because it phosphorylates and inactivates ACC. Here, we designed a fused molecule consisting of a pyrazoloketone-type ACC inhibitor and a recently discovered AMPK activator, aiming to develop a novel combined ACC inhibitor/AMPK activator to regulate fatty acid levels. The designed compound was prepared through a convergent synthetic route. This compound and its methyl ester analogue showed potent ACC2-inhibitory activity with IC50 values of 8.8 and 1.3 μM, respectively. Exomethylene derivatives, obtained from an unexpected side reaction during deprotection, also exhibited ACC2-inhibitory activity.
Published online: 1st December, 2016
■ 2-Arylquinoline Synthesis from Cbz-Protected 2-Aminochalcone Mediated by BF3•Et2O
Tomohiro Maegawa,* Misa Nogata, Takaya Honda, Akira Nakamura, and Yasuyoshi Miki*
*School of Pharmaceutical Sciences, Kindai University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan
Abstract
A novel approach to producing the quinoline skeleton from 2-aminochalcone was developed. Treatment of benzyloxycarbonyl (Cbz)-protected 2-aminochalcones with BF3·Et2O afforded quinoline derivatives via the deprotection of the Cbz group and isomerization of olefin in a one-pot reaction. The reaction of various 2-aminochalcones proceeded to give the corresponding 2-arylquinoline derivatives in good yields. This method is applicable to the rapid synthesis of dubamine.
Published online: 7th November, 2016
■ Syntheses of Partially Brominated Derivatives of Tetra-2-thienylmethane for Three-Dimensionally Extended π-Electron Systems
Kouzou Matsumoto,* Takeshi Suzuki, Yasukazu Hirao, Hiroyuki Kurata, and Takashi Kubo*
*Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-8531, Japan
Abstract
Partially α-brominated derivatives of tetra-2-thienylmethane (Brn-TTM; n = 1–3) were synthesized and isolated in gram quantities. An alternative and more selective preparation of Br3-TTM was also developed. A new π-electron system based on the tetra-2-thienylmethane framework was synthesized from the monobromo derivative of tetra-2-thienylmethane.
Published online: 15th December, 2016
■ Synthesis of 2-Arylamino-1-azaazulenes
Satoru Tsukada,* Makoto Nakazawa, Yuya Okada, Keito Ohtsu, Noritaka Abe, and Takahiro Gunji
*Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
A series of 2-arylamino-1-azaazulenes were synthesized by the Buchwald-Hartwig cross coupling reaction. The resulting compounds were characterized by 1H NMR, 13C NMR, HRMS analyses, and elemental analysis. X-Ray crystallographic analysis revealed that 2-(1-naphthylamino)-1-azaazulene exists in dimeric form with two intermolecular N–H…N hydrogen bonds in its crystal structure.