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
Kiyoshi Tomioka's Special Issues, Vol. 97, No. 1, 2018
Published online: 23rd February, 2018
■ Oxidative Rearrangement of Benzylamines to 4H-3,1-Benzoxazines via Cu/Mn-Promoted Intramolecular C–H Amination/Electrocyclic Reaction Cascade
Chiaki Yamamoto, Kazutaka Takamatsu, Koji Hirano,* and Masahiro Miura*
*Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Abstract
We have developed a copper/manganese-mediated oxidative rearrangement of benzylamines to 4H-3,1-benzoxazines of potent interest in medicinal applications. The reaction proceeds uniquely through the initial copper/manganese-promoted intramolecular C–H amination giving benzazetidine intermediates and subsequent 4π electrocyclic ring opening/6π electrocyclic ring closing cascade. The key to success is the introduction of picolinamide-based N,N-bidentate directing group. The obtained benzoxazines can also be readily hydrolyzed to the corresponding 2-aminobenzyl alcohols, thus indicating that the overall transformations is regarded as the ortho-aminative rearrangement of benzylamines to benzylic alcohols.
Published online: 13th March, 2018
■ Synthesis and Photophysical Properties of 5-N-Arylaminothiazoles with Sulfur-Containing Groups on the Aromatic Ring at the 2-Position
Toshiaki Murai,* Hidenori Furukawa, and Kirara Yamaguchi
*Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu, Gifu 501-1193, Japan
Abstract
5-Amino-2-(4-methylsulfanylphenyl)thiazoles were prepared by reacting 4-methylsulfanylbenzthioamides and N,N-diarylthioformamides. Demethylaiton of the resulting thiazoles gave 4-sulfhydrylphenylthiazoles. Starting from these thiazoles, a range of thiazoles with sulfur-containing functional groups were prepared. Oxidation of the thiazoles also gave thiazoles with sulfenyl and sulfonyl groups. The photophysical properties of a series of thiazoles were determined. The effects of sulfur-containing functional groups on the electronic structures of the thiazoles were elucidated by DFT calculations. Oxidation of the divalent sulfur atoms introduced to thiazoles helped to lower the energy levels of the LUMOs of the resulting thiazoles.
Published online: 26th February, 2018
■ A Short Synthesis of 9-Fluoroellipticine from 5-Fluoroindole
Deborah A. Davis and Gordon W. Gribble*
*6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, U.S.A.
Abstract
A synthesis of 9-fluoroellipticine (1c) from 5-fluoroindole (6) is described that features the regioselective lithiation of 5-fluoro-1-(phenylsulfonyl)indole (7) followed by chemoselective acylation of 3,4-pyridinedicarboxylic anhydride. Subsequent cyclization of keto acid 9 to keto lactam 10 with acetic anhydride and sequential treatment of 10 with methyllithium and sodium borohydride affords 9-fluoroellipticine.
Published online: 31st May, 2018
■ Facile Synthesis of Indolelactones Using Mn(III)-Based Oxidative Substitution-Cyclization Reaction
Takeshi Inoue and Hiroshi Nishino*
*Department of Chemistry, Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1, Chûou-Ku, Kumamoto 860-8555, Japan
Abstract
Based on the oxidation of indole with Mn(OAc)3 in the presence of 1,1-diarylethenes affording 3-vinyl-substituted indoles, a similar oxidation using indole-2-carboxylic acids was evaluated in order to effectively introduce the substituent group to the C-3 position of the indolecarboxylic acids. The coupling reaction followed by oxidative cyclization smoothly proceeded at room temperature in an AcOH-HCO2H mixed solvent to give the desired indolelactones in high yields. The reaction details, the structure determination of the products and a brief reaction mechanism are described.
Published online: 13th April, 2018
■ Computational Study for the Selective Aromatic Nucleophilic Substitution on 4-Dimethylamino-2-methoxy-3-trifluoroacetylquinoline
Norio Ota, Shota Sasakawa, Yasuhiro Kamitori, and Etsuji Okada*
*Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Abstract
The selective nucleophilic substitution on aromatic ring occurs at the 4-position of 4-dimethylamino-2-methoxy-3-trifluoroacetylquinoline 1 by the reaction with various amines to afford the N-N exchanged products solely, and any O-N exchange reactions at the 2-position are not performed. Our DFT calculation study led to a rational explanation of this unique selectivity based on the frontier electron densities (LUMO) of 1 and energies of the Meisenheimer complexes which were assumed to be formed as the intermediates on such substitution course. It was also investigated about the reaction of related 4-dimethylamino-2-methoxyquinolines bearing various electron-withdrawing groups at the 3-position.
Published online: 16th March, 2018
■ Oxidation of 1-Arylcyclohexa-2,5-dienes and Subsequent Double Michael Addition. A Rapid Access to the Büchi Ketone and the Pentacyclic Core of Aspidosperma Alkaloids
Dawood Hosni Ibrahim, Julie Dunet, Frédéric Robert, and Yannick Landais*
*Institute of Molecular Sciences, University of Bordeaux, 351 Cours de la Libération, F-33405 Talence Cedex, France
Abstract
The Pd-catalyzed oxidation of 1-arylcyclohexa-2,5-dienes, resulting from a Birch reductive alkylation, leads to the corresponding arylcyclohexadienones. A careful choice of the substituents on the starting biaryl affords arylcyclohexadieonones, which may then enter into a double Michael addition, opening an access to the tetracyclic core of terpene indole alkaloids of the aspidosperma family. This strategy was used to prepare the Büchi ketone, a key-intermediate in the synthesis of this class of alkaloids, in 6 synthetic operations and 17% overall yield from commercially available 2-aminobiphenyl.
Published online: 5th April, 2018
■ Synthesis and Biological Activities of Acetal Analogs at Position 3 of 10-Methyl-Aplog-1, a Potential Anti-Cancer Lead Derived from Debromoaplysiatoxin
Koutaro Hayakawa, Yusuke Hanaki, Harukuni Tokuda, Ryo C. Yanagita, Yu Nakagawa, Mutsumi Okamura, Shingo Dan, and Kazuhiro Irie*
*Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Oiwakecho, Kitasirakawa, Sakyo-Ku, Kyoto City, Kyoto 606-8502, Japan
Abstract
10-Methyl-Aplog-1 (1), a simplified analog of tumor-promoting debromoaplysiatoxin (DAT), is a potential anti-cancer lead because, unlike DAT, 1 is not tumor-promoting or proinflammatory. However, its synthesis required 23 linear steps with an overall yield of 1.1%. To develop a more synthetically accessible compound, we designed a new analog (2) whose carbon atom at position 4 was replaced with an oxygen atom. Simultaneous construction of the spiroketal at position 7, the acetal at position 3, and the macrolactone ring enabled us to reduce the synthetic steps to produce 2 and its 3-epimer (16) in 18 linear steps with overall yields of 0.30 and 0.67% respectively. Although both analogs retained anti-proliferative activity, it was weaker than that of 1.
Published online: 25th April, 2018
■ Enantioselective Synthesis of Spiro (Isoxazole-Isoxazoline) Hybrid Ligand
Bijan Mohon Chaki, Kazuhiko Wakita, Shinobu Takizawa, Kazuhiro Takenaka, and Hiroaki Sasai*
*The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki, Osaka 567-0047, Japan
Abstract
Enantioselective synthesis of chiral spiro hybrid ligand (R,S)-1 possessing isoxazole and isoxazoline rings as coordination sites was accomplished through a process involving desymmetrized intermediate 5. The key intermediate 5 was readily obtained via chiral Cu-catalyzed mono-acylation of 1,3-diol 3 or enzymatic mono-deacylation of diester 6.
Published online: 14th May, 2018
■ Two New Galloyl Glucosides from the Leaves of Castanopsis fordii
Yong-Lin Huang,* Zhang-Bin Liu, Ya-Feng Wang, Li Ge, Rui-Jie He, Jin-Lei Liu, Ke-Di Yang,* 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
Two new galloyl glucosides, furan-2-carbonyl 6-C-β-D-(6'-O-galloyl)glucopyranoside (1), grasshopper ketone 5-O-β-D-(6'-O-galloyl)glucopyranoside (2), and one known compound 4-quinolone-2-carboxylic acid, were isolated from ethanol extract of the fresh leaves of Castanopsis fordii (Fagaceae). The chemical structures of these compounds were determined by one and two dimensional (1D and 2D)-NMR, liquid chromatography/time-of-flight/mass spectrometry (LC/TOF/MS), chemical evidence, and comparison with the literature.
Published online: 19th December, 2017
■ Concise Approach to Mono- and Disubstituted Luotonin A Analogs and Their Cytotoxicity Test
Natsuko Kagawa,* Kimiko Nishimura, Shinya Abe, Takashi Masuko, and Masahiro Toyota*
*Department of Chemistry, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuencho, Sakai, Osaka 599-8531, Japan
Abstract
A concise approach for the preparation of luotonin A analogs has been developed. The new synthetic route contains an anion-assisted intramolecular double hetero Diels ̶ Alder reaction and a direct oxidative cross coupling reaction. Some synthetic luotonin A analogs show cytotoxic activities against Daudi and Jurkat human cancer cells as potent as camptothecin.
Published online: 26th December, 2017
■ Stereoinversion of a Tertiary Alcohol on a THP Ring: a Recovery Route to an Intermediate for Gymnocin-A
Takeo Sakai, Kayo Aoyama, Rie Oshima, Kyoko Furukawa, and Yuji Mori*
*Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan
Abstract
The stereoinversion of a tertiary alcohol on a tetrahydropyran ring was achieved through a five-step sequence including regioselective dehydration, diastereoselective epoxidation and reduction. This approach offers a recovery route from the diastereomer to the desired tertiary alcohol as part of the synthesis of gymnocin-A.
Published online: 9th February, 2018
■ Synthesis Of 2′(2′,6′)-(Di)Halogenoisoxazolopodophyllic Acids-Based Amides Derived from a Naturally Occurring Lignan Podophyllotoxin and Their Acaricidal Activity
Bingchuan Zhang, Mingqiao Yu, Min Lv,* and Hui Xu*
*Laboratory of Pharmaceutical Design & Synthesis, College of Life Sciences, Northwest A & F University, Xinong Road 22#, Yangling, Shaanxi, 712100, China
Abstract
In continuation of our program to discover natural product-based pesticides, a series of 2′(2′,6′)-(di)halogenoisoxazolopodophyllic acids-based amides were prepared by structural modification of a naturally occurring lignan podophyllotoxin. Meanwhile, their acaricidal activity was evaluated against a typically crop-threatening agricultural insect pest, Tetranychus cinnabarinus. Among all derivatives, especially compounds 10−12 displayed 4.8-7.4 folds more potent acaricidal activity than podophyllotoxin against T. cinnabarinus. This demonstrated that the carboxyl group at their C-2 position of 2′(2′,6′)-(di)halogenoisoxazolopodophyllic acids was very important for the acaricidal activity.
Published online: 2nd February, 2018
■ One-Pot Synthesis of (Z)-N-Substituted Isobenzofuran-1(3H)-imines from Secondary Benzothioamides and Carbonyl Compounds
Kazuhiro Kobayashi* and Takashi Nogi
*Applied Chemistry Field, Chemistry and Biotechnology Course, Department of Engineering, Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Abstract
An efficient one-pot methodology for the synthesis of (Z)-N-substituted isobenzofuran-1(3H)-imines starting from secondary benzothioamides has been developed. The reaction of the starting materials with two equivalents of butyllithium generated 2,N-dilithio-N-alkyl(or aryl)benzothioamides, which were then allowed to react with carbonyl compounds to give, after aqueous treatment, the desired products in satisfactory yields.
Published online: 1st March, 2018
■ Synthesis of N-ω-Phenylalkyl-4-(p-chlorophenyl)-piperidin-4-ol Analogues with Potent Antiproliferative Activity Against HCT-116 Cells
Noriyuki Hatae,* Eiko Kujime, Keigo Yano, Mami Kizuka, Rina Ashida, Tominari Choshi, Takashi Nishiyama, Chiaki Okada, Tatsunori Iwamura, and Teruki Yoshimura*
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
Some opioid analogues, such as morphine and loperamide, were reported to exhibit weak antiproliferative activity against tumor cells. In a study of loperamide analogues, we found that adding an N-ω-phenylalkyl group onto the 4-arylpiperidin-4-ol unit can have important effects on the antiproliferative activity of such compounds against HCT-116 cells. We optimized the distance between the phenyl group and 4-arylpiperidin unit to promote such activity.
Published online: 15th March, 2018
■ Reactions of Pyruvate-Derived Dihydropyrans with Formaldehyde: Synthesis of Functionalized Furopyrans and Related Products
Pandurang V. Chouthaiwale, Ravindra D. Aher, 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
Reactions that afford functionalized furopyrans and/or dimethylene derivatives from pyruvate-derived dihydropyrans and formaldehyde are described.
Published online: 17th April, 2018
■ A New Method of Deuterium Incorporation to TMS-Epoxyalcohol Using Sodium Methylsulfinylmethylide-d5 (NaDMSO-d5)
Yutaro Nanba, Shuhei Tanabe, and Yuichi Kobayashi*
*Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Box B52, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan
Abstract
A reaction of 1-TMS-1,2-epoxyoctan-3-ol with NaDMSO-d5 (Na+ CD3S(O)CD2–), prepared in situ from DMSO-d6 and NaH, afforded non-1-ene-1,1-d2-3,4-diol. Both the anti and syn isomers showed similar reactivity and the stereochemistry was preserved. α-Ethoxyethyl ether of the epoxy alcohol was converted to the corresponding mono-ethoxyethyl ether of the 1-ene-3,4-diol. Hydroboration and hydrogenation of the corresponding TBS ethers afforded compounds with the "CH2CD2OH" and "CH2CD2H" groups, respectively.
Published online: 2nd March, 2018
■ Synthesis of Phenol and Naphthol Derivatives from Furfural
Kentaro Okano, Yuki Murase, Naoki Miyagawa, Kana Ashida, and Atsunori Mori*
*Chemical Science & Technology, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Abstract
Synthesis of phenol and naphthol derivatives was performed from furfural derivatives through cycloaddition with an alkyne and benzyne, respectively. Lewis acid-promoted ring opening of the cycloadducts led to the formation of the corresponding phenol and naphthol derivatives. Amide-directed C–H alkenylation and arylation gave functionalized π-conjugated naphthalene derivatives.
Published online: 17th May, 2018
■ Lewis Acid Catalysis in Intermolecular [2+2] Photocycloaddition of Coumarin-3-carboxamide Bearing 2-Oxazolidinone Auxiliary with n-Propyl Vinyl Ether and Vinyl Pivalate
Kennosuke Itoh,* Junya Matsuura, Hideaki Kamiya, Ryuki Kudo, Yuki Takahashi, Yuta Hashimoto, Kenji Yoza, Ken Tokunaga,* Hideaki Fujii,* and Hiroyuki Suga*
*Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan
Abstract
Intermolecular [2+2] photocycloaddition reactions between 3-(2-oxo- 2H-chromene-3-carbonyl)oxazolidin-2-one with n-propyl vinyl ether and vinyl pivalate were carried out to give [2+2] cycloadducts in excellent yield with perfect regioselectivity. A Lewis acid catalyst (30 mol%) was moderately effective in accelerating the reaction. Furthermore, enantioselective reactions catalyzed by chiral Lewis acid catalysts (30 mol%) were performed to give cycloadducts in excellent yields with up to 13% ee.
Published online: 18th May, 2018
■ Preparation of Optically Active 2,2-Disubstituted 5-Hydroxychromenes by the Enzymatic Resolution of Racemic Esters
Mika Kainuma, Ai Yamada, Kazuaki Katakawa, and Takuya Kumamoto*
*Department of Synthetic Organic Chemistry, School of Pharmaceutical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Abstract
Enzymatic kinetic resolution of racemic esters of 2,2-disubstituted 5-hydroxychromenes was examined. Transesterification of acetate using Amano Lipase PS in the presence of t-BuOH was most effective to give the corresponding optically active acetate in 18% yield and 95% ee. The absolute configuration of the acetate was determined as R based on the conversion to teretifolione B with natural absolute configuration.
Published online: 2nd April, 2018
■ Synthesis of Alkynyl C-Nucleotide Triphosphates Toward Enzymatic Elongation of Artificial DNA
Yutaro Oda, Junya Chiba,* and Masahiko Inouye
*Graduate School of Medicines and Pharmaceutical Sciences for Research, Toyama University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
Four types of alkynyl C-nucleotide triphosphates were synthesized, in which heterocyclic compounds as a non-natural nucleobase were tethered to deoxyribose through acetylene bonds. The non-natural nucleobases are D*, T*, G*, and C*, corresponding to natural A, T, G, and C, respectively, from a hydrogen-bonding pattern of view. All the non-natural triphosphates were found to be a good substrate for terminal deoxynucleotidyl transferase (TdT), a natural nucleic acid-relevant enzyme.
Published online: 17th April, 2018
■ Concise Synthesis of (±)-Aurantioclavine
Hideo Ikota, Chihiro Tsukano,* and Yoshiji Takemoto*
*Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
A synthetic route to (±)-aurantioclavine has been established using a six-step transformation without toxic metal reagents. This synthetic route is useful because it is not only a short-step synthesis but is applicable to gram-scale synthesis of a protected (±)-aurantioclavine.
Published online: 12th April, 2018
■ Metal-Free Oxidative Cross-Coupling of Pyrroles with Electron-Rich Arenes Using Recyclable Hypervalent Iodine(III) Reagent
Koji Morimoto, Toru Kamitanaka, Toshifumi Dohi, and Yasuyuki Kita*
*Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan
Abstract
The facile and clean oxidative cross-coupling reaction of pyrroles has been developed using the recyclable hypervalent iodine(III) reagents having an adamantane core. The recyclable iodine(III) reagent could be recovered from the reaction mixtures as the corresponding reduced forms, i.e., the tetraiodide 2, by a simple solid-liquid separation. By re-oxidizing the recovered 2 to the initial reagent 1a using m-chloroperbenzoic acid (mCPBA), the reagent 1a can be reused.