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
Yasuyuki Kita's Special Issues, Vol. 103, No. 1, 2021
Published online: 9th September, 2020
■ An Alternative Approach to the Development of Near-Infrared Fluorescent Dyes Based on Fluorescein
Akane Katori, Akari Yamagami, Sae Wakabayashi, Kouji Kuramochi, Ayumi Imayoshi, and Kazunori Tsubaki*
*Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Japan
Abstract
In xanthene dyes the upper aryl moiety is often a benzene ring, but in this work an L-shaped dibenzoxanthene dye (4) was synthesized with a five-membered (benz)imidazole ring as the upper aryl moiety. Although 4 was designed with the π-face of the dibenzoxanthene and the π-plane of the aryl moiety as coplanar, the reactivity of the compound at the triaryl carbon was quite high and easily attacked by solvent, such as methanol. The consequent discoloration is caused not only by the external exposure of the triaryl carbon, but also by the greatly reduced LUMO level and increased reactivity to nucleophilic attack when the π-system of the xanthene ring is expanded. The introduction of the 2,6-dimethylphenyl group was found to be effective to avoid nucleophilic attack by solvent. A compound, labeled 9c, with a 2,6-dimethylphenyl group as the aryl moiety, had sufficient stability to solvent, an emission maximum at 828 nm in DMF, and a fluorescence quantum yield of 8%.
Published online: 9th July, 2020
■ Regiodivergent Ring Opening Reactions of 2-Arylated 3-Nitrocyclopropane-1,1-dicarboxylates Leading to Polyfunctionalized Dipoles
Haruyasu Asahara,* Rikiya Kamidate, and Nagatoshi Nishiwaki*
*Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0821, Japan
Abstract
Two kinds of Lewis acid induced ring-opening reactions of 2-aryl-3-nitrocyclopropane-1,1-dicarboxylates proceeded to afford 5-aryl-2-isoxazolines and γ-keto acid derivatives, respectively. Different ring-opening modes could be controlled by choosing the ligand or solvent.
Published online: 16th September, 2020
■ Synthesis of (Trifluoromethyldiazirinyl)phenylboronic Acid Derivatives for Photoaffinity Labeling
Manami Hashinoki, Natsumi Kurokawa, Yuta Murai, Zetryana Puteri Tachrim, Yasuko Sakihama, Takeyuki Suzuki, and Makoto Hashimoto*
*Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-9, Nishi-9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan
Abstract
Trifluoromethylphenyldiazirine is one of the most reliable photophores for photoaffinity labeling during functional analysis of biologically active compounds. Phenylboronic acid derivatives containing trifluoromethyldiazirinyl moiety have not yet been reported. The construction of the photophore was achieved using (3-formylphenyl)boronic acid and (4-formylphenyl)boronic acid pinacol esters effectively.
Published online: 23rd September, 2020
■ Dirhodium(II)-Catalyzed ortho C–H Amination of N-Alkyldiarylamines
Motoki Ito,* Mamiko Mori, Tomoya Nakagawa, Miki Hori, Kazuhiro Higuchi, and Shigeo Sugiyama*
*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588,
Abstract
Dirhodium(II)-catalyzed ortho C–H amination of N-alkyldiarylamines has been developed. The C(sp2)–H amination proceeded with high preference over C(sp3)–H amination to provide N-aryl-o-phenylenediamines in up to 80% yield. With the use of unsymmetric diarylamines as substrates, selective amination of one of two distinct aromatic rings was also achieved.
Published online: 29th October, 2020
■ Synthesis of 1-Methoxy-1H-indoles with a Heterocyclic Moiety via Unstable Indole Isothiocyanate by Using Enzyme from Brassicaceae Plant
Kaori Ryu, Seikou Nakamura,* Koya Miyagawa, Souichi Nakashima, and Hisashi Matsuda*
*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan
Abstract
A synthesis of five 1-methoxy-1H-indole derivatives with imidazole, pyrazole, 1H-1,2,3-triazole, and 1H-1,2,4-triazole moieties was achieved by focusing on the formation mechanism of plant constituents. The objective 1-methoxy-1H-indole derivatives were obtained in situ (in one step) through the reaction of an unstable 3-(isothiocyanatomethyl)-1-methoxy-1H-indole, which was derived from neoglucobrassicin and plant enzyme myrosinase, and a heterocyclic compound. We have great hopes that this method would be useful for the development of medicinal seeds.
Published online: 28th October, 2020
■ Stereoselective Alkylation of Oxathiazinane N,O-Ketals for the Construction of Aza-Quaternary Carbon Centers
Hisanori Nambu, Eri Tanaka, Mai Okada, Chiaki Hirosawa, Narumi Noda, Tomoya Fujiwara, and Takayuki Yakura*
*Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
Abstract
Stereoselective construction of aza-quaternary carbon centers was achieved using the alkylation of oxathiazinane N,O-ketals prepared by Rh(II)-catalyzed C–H amination of sulfamates. The addition of alkyl Grignard reagents into N,O-ketals in the absence of any Lewis acid proceeded stereoselectively to provide the corresponding alkylated products with an aza-quaternary carbon center in high yields. The obtained product could be converted into an α-amino alcohol derivative, which is a potential synthetic intermediate for sphingofungin F and its derivatives.
Published online: 26th October, 2020
■ Synthesis and Structure-Activity Relationship Study of 1,12-Dicarba-closo-dodecaborane-based Triol Derivatives as Nonsecosteroidal Vitamin D Analogs
Shinya Fujii, Ryota Sekine, Atsushi Kano, Hiroyuki Masuno, Emiko Kawachi, Tomoya Hirano, and Hiroyuki Kagechika*
*Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10, Surugadai, Kanda, Chiyoda-ku 101-0062, Japan
Abstract
The secosteroidal hormone 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is a specific ligand of nuclear vitamin D receptor (VDR), and novel vitamin D analogs are promising candidates for multiple clinical applications. We previously developed a series of 1,12-dicarba-closo-dodecaborane (p-carborane) derivatives as nonsecosteroidal VDR agonists. Here, we report the synthesis and structure-activity relationship of p-carborane-based nonsecosteroidal vitamin D analogs bearing a nitrogen or a sulfur atom in the linker structure. Biological evaluation revealed that the structure–activity relationships of amine derivatives and sulfide derivatives are different, and therefore the choice of the linker structure significantly affects the activity. We also found that benzylamine structure could be a lead scaffold for novel vitamin D analogs. The structure–activity relationships presented here should be helpful in further development of nonsecosteroidal vitamin D analogs.
Published online: 13th May, 2020
■ Conjugate Addition Reaction of Indole to Protected 2-Amino-1-nitroethenes Mediated by Silica Gel
Kenichi Murai,* Shuji Miyazaki, and Hiromichi Fujioka*
*Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, Osaka 560-0871, Japan
Abstract
We have developed a silica-gel-mediated route for the conjugate addition of indole to protected 2-amino-1-nitroethenes for the synthesis of 1-indolyl-1,2-ethanediamines. This is the first demonstration of indole as the nucleophile for addition to protected 2-amino-1-nitroethenes.
Published online: 14th May, 2020
■ Synthesis of a Pentacoordinate Germanium Compound Possessing a γ-Lactone and a Dative-Bonding Carboxylic Acid
Hiroki Tanimoto,* Daiki Toumori, Tsumoru Morimoto, and Kiyomi Kakiuchi*
*Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan
Abstract
A pentacoordinate germanium compound consisting of a spirocyclic dilactone-like structure was synthesized. Both radical and oxidation synthetic routes afforded the diphenylgermanium dicarboxylic acid compound. Then, mono-dearylation by acid treatment successfully delivered a hypercoordinate germane product. X-Ray crystallographic analysis revealed that the product adopted trigonal bipyramidal geometry in which a γ-lactone ring and a dative-bonding carboxylic acid moiety were incorporated.
Published online: 13th May, 2020
■ Synthesis of Pyrrolo[1,2-c]pyrimidines
Easha Narayan, Liangfeng Fu, and Gordon W. Gribble*
*6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, U.S.A.
Abstract
The synthesis of several new pyrrolo[1,2-c]pyrimidines from the base-induced condensation of pyrrolo-2-carbaldehydes with either TosMIC (toluenesulfonylmethyl isocyanide) or ethyl isocyanoacetate is described, along with the preparation of novel bis(pyrrolo[1,2-c]pyrimidines).
Published online: 23rd June, 2020
■ Bifunctional-Benzothiadiazine-Catalyzed Regio- and Stereoselective Aldol Reactions Using A 1,3-Acetonedicarboxylic Acid Monoester
Yusuke Tokuhiro, Noboru Hayama, Yusuke Kobayashi, and Yoshiji Takemoto*
*Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
Regio- and stereoselective decarboxylative aldol reactions of a 1,3-acetonedicarboxylic acid monoester were achieved using an aminobenzothiadiazine organocatalyst. The products were obtained with perfect regioselectivity and moderate to good enantioselectivity using various aromatic aldehydes. Subsequently, the thus obtained adducts were efficiently converted into various chiral building blocks.
Published online: 4th September, 2020
■ Palladium on Carbon–Catalyzed Oxidative Transformation of Benzylic Ethers
Ryoya Takakura, Shoko Kuwata, Kouki Nakano, Naoki Yasukawa, Hironao Sajiki,* and Yoshinari Sawama*
*Laboratory of Organic Chmistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi 501-1196, Japan
Abstract
Palladium on carbon (Pd/C)-catalyzed oxidative transformations of primary and secondary benzylic ethers in ethylene glycol as a solvent and reagent in an oxygen atmosphere produced the corresponding hydroxyethyl esters and cyclic ketals, respectively. Commercially-available and heterogeneous Pd/C was easily removed by filtration, and molecular oxygen was used as a clean oxidant.
Published online: 11th September, 2020
■ Transition Metal-Free O-Arylation of Quinoxalin-2-ones with Diaryliodonium Salts
Masami Kuriyama,* Yuki Mochizuki, Tsubasa Miyagi, Kosuke Yamamoto, Yosuke Demizu, and Osamu Onomura*
*Graduate School of Biomedical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
Abstract
The transition metal-free O-arylation reactions of quinoxalin-2-ones with diaryliodonium salts have been achieved, and desired 2-aryloxyquinoxalines were readily obtained in moderate to high yields. This method proved to be compatible with a series of diaryliodonium salts as well as a set of quinoxalin-2-ones.
Published online: 9th November, 2020
■ Design, Synthesis, Physical Properties and Indoleamine 2, 3-Dioxygenase 1 Inhibitory Activity of Substituted Indole Derivatives with N-H, N-Methoxymethyl, or N-Mehylthiomethyl Group toward Fragment-Based Drug Discovery
Kenta Hayami, Yuichi Kuboki, Katsumi Ohta, Bangzhong Lin, Megumi Fumimoto, Kazuto Nunomura, Jun-Ichi Haruta , Kenichi Murai, Hiromichi Fujioka, Akira Asai, and Mitsuhiro Arisawa*
*Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, Osaka 560-0871, Japan
Abstract
We designed and prepared N-H, N-CH2OMe(MOM), and N-CH2SMe (MTM) forms of various substituted indoles, using a docking study, as a small fragment library toward fragment-based drug discovery (FBDD) and evaluated their indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitory activities and physical properties.
Published online: 13th November, 2020
■ De Novo Approach to Izidines via A Gold-Catalyzed Hydroamination–N-acyliminium Ion Cyclization of Acyclic Ynamides
Kenji Sugimoto,* Shota Mizuno, Misaki Shirato, Kosuke Tanabe, and Yuji Matsuya*
*Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Abstract
A gold(I)-catalyzed novel domino reaction of acyclic ynamides yielding nitrogen-fused bicyclic skeletons was described. The reaction with 10 mol% JohnPhosAuNTf2 and stoichiometric amount of PhCO2H enables constructions of quinolizidine and indolizidine skeleton having tetrasubstituted carbon center. Especially in the case of quinolizidine synthesis, the quaternary stereogenic center could be furnished under highly diastereoselective manner.
Published online: 3rd December, 2020
■ Concise Synthesis of an Amide-Functionalized [7]Helicene-like Molecule via Intramolecular Amidation
Yongning Xing, Masanori Nikaido, Takuya Murai, Shohei Hamada, Yusuke Kobayashi, Takahiro Sasamori, Takeo Kawabata, and Takumi Furuta*
*Department of Pharmaceutical Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan
Abstract
A concise synthesis of an amide-functionalized [7]helicene-like molecule was achieved via the intramolecular amidation of an in-situ-generated biaryl δ-amino acid derivative. An X-ray analysis of racemic mixture of this helicene-like molecule revealed a helically twisted π-system and that the (M)- and (P)-isomers associate pairwise via hydrogen-bonding interactions, which results in a one-dimensional columnar packing in the crystal structure.