HETEROCYCLES

Published online: 6th December, 2019

■ Synthesis and Evaluation for Biological Activities of 2-Thio-Acylated Thiazoles Containing Pyrazole Moiety

Eiichi Masumoto, Nobuhiro Kashige, Hayate Nagabuchi, Fumi Okabe-Nakahara, and Hiroshi Maruoka*

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

An approach to the synthesis of novel 2-thio-acylated thiazoles containing pyrazole moiety is described. The pyrazole-thiazolethione derivative as the key building block for bis-heterocycles was formed via a Knoevenagel-type condensation of rhodanine with pyrazol-3-one. Thermal treatment of the pyrazole-thiazolethione derivative with acid anhydride and/or chloride in refluxing toluene caused diacylation reaction to give the corresponding 2-thio-acylated thiazoles containing pyrazole moiety. All the synthesized compounds were characterized by spectroscopic analysis and were tested for their DNA cleavage activity in vitro. Furthermore, they were evaluated for their antifungal activity against Candida albicans and Saccharomyces cerevisiae.

Published online: 26th November, 2019

■ Some Hybrid Linker Mode C2-Symmetrical 1,3,5-Triazine Derivatives and Their Biological Evaluation

Nobuko Mibu, Makoto Furutachi, Yusuke Inoue, Yuka Fujita, Yumemi Matsumoto, Yuki Kawano, Syoko Tomonaga, Junko Matsuyama, Kanae Yamada, Ryo Sato, Kazumi Yokomizo, Jian-Rong Zhou, Shunsuke Shimomura, Kaori Ota, and Kunihiro Sumoto*

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

We report the preparation of some new C2-symmetrical multivalent hybrid-type molecules having a methylene linker group and 1,3,5-triazine (TAZ) recognition moieties in the molecule and we also report the results of biological evaluation of their anti-herpes simplex virus type 1 (anti-HSV-1) activity and cytotoxic activity against Vero cells. All mid-size C2-symmetrical multivalent hybrid-type molecules (3a-2, 3a-4, 3b-2, 3b-3, 3b-4) showed considerably high levels of anti-HSV-1 activity (EC50 = 7.6 ~ 95.6 μM) with low levels of cytotoxicity (CC50 > 200 μM) against Vero cells. Among the tested compounds, the hybrid-type C2-symmetrical multivalent molecule (3a-4) seems to be an interesting new lead in the search for new hybrid-type multivalent mid-size antiviral compounds.

Published online: 25th November, 2019

■ One-Pot Synthesis of 3-(Guaiazulen-3-yl)dihydro-1H- indol-4(5H)-ones via Domino Reaction

Lu Zhang, Dao-Lin Wang,* Jin-Juan Xing, and Lin Liu

*College of Chemistry and Chemical Engineering, Bohai University, 19, Keji Rd., New Songshan District, Jinzhou City, Liaoning Province 121001, China

Abstract

A facile and efficient one-pot procedure for the preparation of 3-(guaiazulen-1-yl)dihydro-1H-indol-4(5H)-ones by a catalyst-free, three- component reaction of guaiazulene, methylglyoxal and enaminones under mild conditions in good yield is reported.

Published online: 25th November, 2019

■ Sugar Based γ-Amino Alcohol Organocatalyst for Asymmetric Michael Addition of β-Keto Esters with Nitroolefins

Divakar Ganesan, Madhu Chennapuram, Zubeda Begum, Chigusa Seki, Yuko Okuyama, Eunsang Kwon, Koji Uwai, Michio Tokiwa, Suguru Tokiwa, Mitsuhiro Takeshita, and Hiroto Nakano*

*Division of Sustainable and Environmental Engineering, Graduate School of Engineering, Muroran Institute of Technology, 27-1 Mizumoto, Muroran, Hokkaido 050-8585, Japan

Abstract

Sugar based γ-amino alcohol was used in asymmetric Michael addition of β-keto esters with nitroolefins for the first time affording the corresponding several chiral Michael adducts bearing quaternary chiral carbon center in moderate to good chemical yields and stereoselectivities (up to 98%, up to dr. 95:5, up to 84% ee).

Published online: 21st November, 2019

■ Recent Advances in Synthetic Hetaryne Chemistry

Yu Nakamura, Suguru Yoshida,* and Takamitsu Hosoya*

*Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10, Surugadai, Kanda, Chiyoda-ku 101-0062, Japan

Abstract

Recent advances in synthetic hetaryne chemistry are reviewed. Various methods for the generation of hetaryne intermediates from several types of precursors enabled facile syntheses of a broad range of heteroaromatic compounds including natural products.

Published online: 14th November, 2019

■ Piperidine and Azetidine Formation by Direct Cyclization of Diols with N-Nonsubstituted Sulfonamide under the Mitsunobu Conditions Utilizing (Cyanomethylene)tributylphosphorane (CMBP) and Its Application to the Synthesis of Lupinine

Hiroto Kaku,* Yuhei Sonoda, Hideyuki Hishida, Yuri Taniguchi, Akiko Kubo, Takumi Hamaguchi, Mitsuyo Horikawa, Makoto Inai, Kei Kitamura, and Tetsuto Tsunoda*

*Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-machi, Tokushima, 770-8514, Japan

Abstract

(Cyanomethylene)tributylphosphorane (CMBP) can promote the Mitsunobu reaction of 1,3- and 1,5-diols with N-nonsubstituted sulfonamides, such as tosylamide (TsNH2) and 3,3-dimethoxypropylsulfonamide (DimpsNH2), to prepare azetidine and piperidine ring systems directly. Utilizing this methodology, lupinine, a biologically active piperidine alkaloid, was synthesized.

Published online: 13th November, 2019

■ Isochromophilol A, a New Azaphilone Isolated from Penicillium sp. RO369, a Leaf Litter Inhabiting Fungus from Tsuga diversifolia

Kan'ichiro Ishiuchi,* Dai Hirose, Yoriko Takahashi, Ryu Miyagawa, Kohei Watanabe, and Susumu Kitanaka*

*Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-Dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan

Abstract

A new sclerotiorin-type azaphilone, isochromophilol A (1), was isolated from Penicillium sp. RO369 associated with Tsuga diversifolia, along with eight known compounds (2−9). The structure of 1 was elucidated on the basis of spectroscopic data. Isochromophilol A (1) (16 μg) showed weak anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity with an inhibition diameter of 8.8 ± 1.0 mm

Published online: 7th November, 2019

■ One-Pot Synthesis of Pyrrolo[2,1-α]isoquinolines via Tandem Reactions of Vinylselenonium Salt, 2-Bromoethanones, and Isoquinoline

Qi Sun, Minghong Liao, Yan Zhao, Yunxia Li, Shanshan Liu, Deshou Mao,* and E Tang*

*School of Chemical Science and Technology, Yunnan University, No. 2 Green Lake North Road, Kunming 650091, China

Abstract

An convenient and one-pot synthesis of pyrrolo[2,1-a]isoquinolines via the tandem reaction of methyl(phenyl)vinylselenonium salt with isoquinoline and 2-bromoethanones has been developed, which features very mild conditions, available substrates, simple experimental procedures, moderate to good yields, and wide functional group tolerance.

Published online: 6th November, 2019

■ A Highly Selective Fluorescence-Enhanced Probe for the Rapid Detection of SO2 Derivatives and Its Bio-Imaging in Living Cells

Yaogen Zhou, Yiwei Zhou, Hongying Wang,* and Baoquan Chen*

*School of Chemistry and Chemical Engineering, Tianjin University of Technology, 391 Binshui Xidao, Xiqing District Tianjin 300384, China

Published online: 1st November, 2019

■ Asymmetric Construction of Heterocycles via Dearomative Coupling and Addition Reactions of Phenol and Aniline Derivatives

Kotaro Kikushima,* Hideyasu China, and Toshifumi Dohi*

*College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

Abstract

Efficient methods for the formation of chiral heterocycles are considerably important in the synthesis of naturally-occurring compounds and pharmaceutical products. This review highlights the formation of chiral heterocycles through dearomative bond-formations as the key reactions, wherein the phenol or aniline derivatives serve as the nucleophiles. Transition-metal-catalyzed intramolecular coupling reactions in the presence of chiral ligands afford the enantioenriched multicyclic compounds bearing heterocycles. Chiral bifunctional organocatalysts induce the formation of dearomative coupling products, which could be converted to heterocycles through further transformations.

Published online: 30th October, 2019

■ Facile Synthesis of (Guaiazulen-1-yl)-1H-pyrroles via Paal-Knorr Reaction

Lu Zhang, Dao-Lin Wang,* Jin-Juan Xing, and Lin Liu

*College of Chemistry and Chemical Engineering, Bohai University, 19, Keji Rd., New Songshan District, Jinzhou City, Liaoning Province 121001, China

Abstract

An efficient and simple method for the synthesis of (guaiazulen-1-yl)-1H-pyrroles was described. The construction of this new heteroarylazulene system was achieved by a the Paal-Knorr reaction of 3-acetyl-4-(guaiazulen-1-yl)hexane- 2,5-dione (4), easily preparation by a three-component condensation of guaiazulene (1), methylglyoxal (2) and acetylacetone (3), with primary amines (5).

Published online: 23rd October, 2019

■ Design, Synthesis and Structure-Activity Relationship Study of Pyrilamine Derivatives as Histone Deacetylase Inhibitors

Seiya Hiranaka, Mayumi Arata, Akiko Nakata, Akiko Tanaka, Yoshinobu Hashizume, Norio Kudo, Akihiro Ito, Minoru Yoshida, Shinichi Uesato, Yasuo Nagaoka, and Takaaki Sumiyoshi*

*Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan

Abstract

For the study on the structure-activity relationship of pyrilamine-based histone deacetylase inhibitor 1, we focused on the structures of its benzyl and dimethylamino groups. Of the synthesized novel pyrilamine derivatives 2–7, compound 2 enhanced potency against hERG inhibition, as well as decreased molecular weight and topological polar surface area.

Published online: 16th October, 2019

■ N-Glycosylation Reaction of Thio-Glycoside Using Hypervalent Iodine(Ill) Reagent

Koji Morimoto, Kana Yanase, Takumi Ikeda, Chihiro Uchikawa, Yasuyuki Kita,* and Tetsuya Kajimoto*

*Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

Abstract

We discovered that the hypervalent iodine(III) reagent could mediate the N-glycosylation reaction using the thio-glycoside donors with triazoles.  By using this method, glycosyl triazole could be easily synthesized under mild reaction conditions.

Published online: 16th October, 2019

■ Synthesis of Cycloalkyl/Steroidal Heteroaryl Sulfides Using Rhodium-Catalyzed Heteroaryl Exchange Reaction

Mieko Arisawa,* Katsuya Nakai, Tomoki Yamada, Ren Suzuki, and Masahiko Yamaguchi*

*Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan

Abstract

Cycloalkyl heteroaryl sulfides are efficiently synthesized by the single-bond cleavage and exchange reaction of S-cycloalkyl thioesters and heteroaryl ethers without using a base. The method is applicable to steroids at the A- and D-rings, and provides diverse heteroarylthiolated steroids with five- and six-membered heteroarenes.

Published online: 10th October, 2019

■ Lewis Acid Mediated Synthesis of Indolizidine Derivatives

Sambasivarao Kotha* and Sunil Pulletikurti

*Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India

Abstract

Here, we have reported a short and efficient BF3•Et2O catalyzed synthesis of indolizidine derivatives. Morever, we have expanded this strategy to synthesize oxa-aza-cyclic derivatives. The stereochemistry of the indolizidine derivative 16 was confirmed by X-ray studies.

Published online: 10th October, 2019

■ Protonation-Assisted Conjugate Addition of Axially Chiral Enolates: Asymmetric Synthesis of β-Lactams with Contiguous Tetrasubstituted Stereocenters from α-Amino Acids via Memory of Chirality

Pan Yang, Tomoyuki Yoshimura, Takahiro Sasamori, Norihiro Tokitoh, Kazuhiro Morisaki, and Takeo Kawabata*

*Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan

Abstract

A method for asymmetric synthesis of highly strained β-lactams with contiguous two tetrasubstituted stereocenters from readily available α-amino acids has been developed via MOC strategy. In situ protonation of the labile β-lactam enolate intermediates formed through 4-exo-trig cyclization of the axially chiral enolates generated from α-amino acid derivatives seems to be the key to successfully produce highly strained β-lactams. A salient feature of this transformation is that a proton source does not quench axially chiral enolate C, but accelerate the overall reaction by protonation of the intermediary β-lactam enolate D.

Published online: 9th October, 2019

■ Ligand Assessment for the Suzuki-Miyaura Cross Coupling Reaction of Aryl and Heteroaryl Bromides with n-Butylboronic Acid. The Advantages of Buchwald’s S-Phos

Thomas Jagusch, Sven Nerdinger, Bernd Lehnemann, Stefan Scherer, Andreas Meudt, Victor Snieckus,* Sandro Neuner, and Herwig Schottenberger

*Department of Chemistry, Queen's University, 90 Bader Lane K7L 3N6, Canada

Abstract

An investigation of biarylphosphine ligands for the Suzuki-Miyaura cross coupling reaction of aryl and heteroaryl bromides with n-butylboronic acid is presented. The results obtained on ligand modification and aryl as well as heteroaryl bromides variation represent a significant improvement in the state of the art of alkylboronic acid cross coupling methodology.

Published online: 8th October, 2019

■ Synthesis of Lactonized Valoneoyl Group-Containing Ellagitannins, Oenothein C and Cornusiin B

Hitoshi Abe,* Haruka Imai, Daichi Ogura, and Yoshikazu Horino

*Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan

Abstract

The total synthesis of two ellagitannins, oenothein C and cornusiin B, which involve a lactonized valoneoyl group (LVG) in the molecules, was accomplished starting from glucose and gallic acid. Classical Ullmann coupling reactions were effective for preparation of the key intermediate, the lactonized valoneic acid derivative, which was subjected to a condensation reaction with glucose, and finally converted to the ellagitannins.

Published online: 8th October, 2019

■ Synthetic Studies on Keramaphidin B: Formation of a Macrocyclic Ring by Intramolecular Diels-Alder Reaction

Hiroki Shimoda, Takahiro Shibata, Daisuke Sekine, and Masahisa Nakada*

*Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

Abstract

The possibility of constructing the macrocyclic ring of keramaphidin B via an intramolecular Diels-Alder (IMDA) reaction has been investigated. The IMDA reaction of a substrate possessing dihydropyridone and diene moieties, which were tethered by an alkyl chain including a linear triple bond, was found to proceed in the presence of SnCl4 at 80 °C.

Published online: 8th October, 2019

■ Benzylic Oxidation and Functionalizations of Xanthenes by Ligand Trasfer Reactions of Hypervalent Iodine Reagents

Toshifumi Dohi,* Keina Komiyama, Shohei Ueda, Nobutaka Yamaoka, Motoki Ito, and Yasuyuki Kita*

*Research Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

Abstract

The benzylic oxidation, amidation, and unprecedented heteroarylation proceed at room temperature using iodosobenzene, (sulfonylimido)iodobenzenes, and diaryliodonium(III) salts are described for the direct Csp3-H functionalizations of xanthene molecules. This study has demonstrated that hypervalent iodine reagents serve as unified synthetic tools for versatile xanthene Csp3-H transformations based on the radical and SET oxidation processes.

Published online: 7th October, 2019

■ Synthesis and Optical Properties of L-Shaped Dinaphthofluoresceins with Two Peripheral Hydroxy Groups

Hikari Yamashita, Chihiro Minari, Eriko Azuma, Kouji Kuramochi, Ayumi Imayoshi, and Kazunori Tsubaki*

*Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan

Abstract

The four compounds 6 and 8–10 having the same L-shaped dinaphthofluorescein skeleton were constructed. The only structural differences among these four compounds were the positions of the two peripheral hydroxy groups. Their dianion forms are a resonance system, thus 6 and 8–10 were expected to exhibit similar optical properties such as the maximum absorption wavelength, molar absorptivity, maximum emission wavelength and fluorescence quantum yield. However, 6 and 8‒10 showed quite different optical properties. For example, the maximum absorption wavelengths of 6, 8, 9 and 10 in aqueous pH 11 solution were 650 nm, 733 nm, 558 nm and 746 nm, respectively. Thus, the positions of the two peripheral hydroxy groups on the same skeleton significantly affected the optical properties.

Published online: 7th October, 2019

■ Trialkylsulfonium and Tetraalkylammonium Salts as Hydrogen-Bonding Catalysts in an Aza-Diels-Alder Reaction: Experimental and Computational Studies

Masahiro Yamanaka,* Ayaka Mochizuki, Takumi Nakamura, Keiji Maruoka, and Seiji Shirakawa*

*Department of Chemistry, Faculty of Science, Rikkyo University, 3-34-1 Nishiikebukuro, Toshima-ku, Tokyo 171-8501, Japan

Abstract

Hydrogen-bonding catalysis by cyclic trialkylsulfonium and tetraalkylammonium salts in an aza-Diels-Alder reaction was investigated. Among the examined onium salt catalysts, cyclic trialkylsulfonium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate possessing a non-coordinating counter anion was the most effective. Details of the activation modes of cyclic trialkylsulfonium and tetraalkylammonium salts were discussed on the basis of DFT calculation.

Published online: 3rd October, 2019

■ α-L-Vancosamine Aryl C-Glycosides, Less Stable Anomers: A Problem in Synthesis of Pluramycin-Class Antibiotics

Yoshio Ando, Hiromune Asahina, Kei Kitamura, Takashi Matsumoto, and Keisuke Suzuki*

*Depatrtment of Chemistry, Tokyo Institute of Technology, 2-12-1,Oh-Okayama, Meguro-ku, Tokyo 152-8552, Japan

Abstract

The pluramycin-class antibiotics have attracted considerable synthetic interest by their bioactivities and unique chemical structures. By the thermodynamic disadvantage, the selective formation of the aryl α-C-glycoside of an L-vancosamine motif, commonly embedded in this class of natural products, has been one of the problems in their total synthesis. This paper summarizes the stereochemical behavior of the pluramycin-class natural products and reports the results of our model study to address this issue by examining three L-vancosaminyl donors under Lewis acidic conditions.

Published online: 2nd October, 2019

■ Mechanistic Studies of Nickel(II)-Catalyzed Direct Alcoholysis of 8-Aminoquinoline Amides

Hiroyuki Morimoto,* Walaa Akkad, Toru Deguchi, and Takashi Ohshima*

*Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

Abstract

This paper describes the mechanistic aspects of nickel(II)-catalyzed direct alcoholysis of 8-aminoquinoline amides. Kinetic experiments suggested that the nickel(II) catalyst existed in an oligomeric form in the resting state, and the 8-aminoquinoline generated after cleavage coordinated to the nickel(II) catalyst to decelerate the reaction. In addition, density functional theory calculations revealed that the reactions proceeded via the intermediate with N,N,O-tridentate coordination of 8-aminoquinoline amides to the nickel(II) metal center, and that the alcoholysis reaction did not involve deprotonation of the N–H bond of 8-aminoquinoline amides, in contrast to the proposed mechanism for C–H bond functionalization reactions of 8-aminoquinoline amides.

Published online: 2nd October, 2019

■ Development of Near-Infrared Fluorescent Probes with Large Stokes Shifts for Non-Invasive Imaging of Tumor Hypoxia

Kensuke Okuda, Bahaa G. M. Youssif, Ryosuke Sakai, Takahiro Ueno, Takayuki Sakai, Tetsuya Kadonosono, Yasuyuki Okabe, Ola I. Abdel Razek Salem, Alaa M. Hayallah, Mostafa A. Hussein, Shinae Kizaka-Kondoh, and Hideko Nagasawa*

*Laboratory of Pharmaceutical　& Medicinal Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan

Abstract

A series of near-infrared (NIR) fluorochromes with large Stokes shifts was designed, synthesized, and evaluated for application in non-invasive imaging of tumor hypoxia. Each NIR fluorescent hypoxia probe comprised a tricarbocyanine dye and a 2-nitroimidazole-containing moiety as a hypoxia marker that binds to cellular nucleophiles via bioreductive activation under hypoxic conditions. Nucleophilic displacement of the amino-nucleophilic linker moiety of heptamethine cyanine dyes having a 2-chloro-1-cyclohexenyl ring and a 2-nitroimidazole moiety yielded various fluorochromes with different hydrophilicity. These exhibited long emission wavelengths (747–758 nm) with large Stokes shifts (111–125 nm) and high quantum yield (0.04–0.34). GPU-210, 297, and 316 showed significantly higher levels of fluorescence under hypoxic than under normoxic conditions on treating SUIT-2/HRE-Luc pancreatic cancer cells. Among these, only GPU-316 showed significant fluorescence intensity in tumor tissue in in vivo fluorescence imaging of mouse xenograft models.

Published online: 1st October, 2019

■ Synthesis of 2-Amino-1,3-benzoselenazole via Metal-Free Cyclization from Isothiocyanate and Bis(o-aminophenyl)diselenide

Hayato Ichikawa,* Naoka Miyashi, Yui Ishigaki, and Minako Mitsuhashi

*Department of Applied Molecular Chemistry, College of Industrial Technology, Nihon University, 1-2-1, Izumi-cho, Narashino, Chiba 275-8575, Japan

Abstract

Amino-1,3-benzoselenazoles were generated from the reactions of bis(o-aminophenyl)diselenide and various isothiocyanates under metal-free cyclization conditions. The cyclization of isothiocyanate bearing bulky substituents proceeded in excellent yields because the amounts of byproducts generated were reduced. Acid hydrolysis of acetamide produced 2-amino-1,3-benzoselenazole (4).

Published online: 1st October, 2019

■ Extraction Properties of 4-Tetra(hydroxyphenyl)BTPhen in Liquid-Liquid Extraction Systems with Cyclohexanone/Octanol or in a Solid-Phase Extraction System

Ashfaq Afsar, Jasraj S. Babra, Petr Distler, Laurence M. Harwood,* Iain Hopkins, Jan John,* James Westwood, and Zoe Y. Selfe

*Department of Nuclear Chemistry, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Břehová 7, 11519 Prague 1, Czech Republic

Abstract

The extraction properties of tetra(4-hydroxyphenyl)BTPhen have been investigated. Liquid-liquid extraction studies in proposed SANEX diluents, cyclohexanone and 1-octanol, indicate that actinide-lanthanide separation is superior in cyclohexanone; whereas actinide-actinide separation is more efficient in 1-octanol. Immobilization of the ligand onto a silica support results in the separation factor becoming dependent upon the concentration of nitrate anions in the aqueous phase. The immobilized ligand was also applied to the extraction of transition metals, resulting in >70% uptake of all transition metals examined, in the presence of alkali and alkaline earth metals.

Published online: 30th September, 2019

■ A New Entry to the Synthesis of (±)-β-Lysine

Keisuke Fukaya, Yuri Kono, Makoto Hibi, Yasuhisa Asano, and Daisuke Urabe*

*Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398, Japan

Abstract

A 3-step synthesis of (±)-β-lysine from ethyl sorbate featuring the aza-Diels-Alder reaction is described.

Published online: 25th September, 2019

■ Novel Trifluoromethylated Spiro-1,3,4-thiadiazoles via [3+2]-Cycloadditions of 2,3-Diphenylcyclopropenethione with Selected in situ-Generated Nitrile Imines Derived from Trifluoroacetonitrile

Greta Utecht-Jarzyńska, Marcin Jasiński,* Kamil Świątek, Grzegorz Mlostoń, and Heinz Heimgartner*

*Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland

Abstract

The in situ-generated N-aryl nitrile imines derived from trifluoroacetonitrile react efficiently with 2,3-diphenylcyclopropenethione to give spirocyclic 1,3,4-thiadiazole derivatives as products of a regio- and chemoselective (3+2)-cycloaddition in good to excellent yields. A stepwise mechanism via initial nucleophilic attack of the S-atom onto the electrophilic C-atom of the electron-deficient 1,3-dipole leading to a zwitterionic intermediate is postulated to explain these formal (3+2)-cycloaddition reactions. The presence of the CF3 group is necessary to activate the nitrile imine for the efficient trapping of the cyclopropenethione. These are the first examples of a successful reaction of this C=S dipolarophile affording 1,3,4-thiadiazoles as formal (3+2)-cycloadducts.

Published online: 25th September, 2019

■ An Approach to a 2-Hydroxy-3-phenyldibenzofuran Skeleton Based on Rh(PPh3)3Cl-Catalyzed [2+2+2] Cycloaddition between a 1-Ethynyl-2-(ethynyloxy)benzene and an (Alkoxyethynyl)benzene

Daisuke Sato, Kenshu Fujiwara,* Yoshihiko Kondo, Uichi Akiba, and Tetsuo Tokiwano

*Graduate School of Engineering Science, Department of Life Science, Akita University, 1-1 Tegatagakuen-machi, Akita 010-8502, Japan

Abstract

A Rh(PPh3)3Cl-catalyzed [2+2+2] cycloaddition of a 2-(trimethylsilylethynyl)-1-(ethynyloxy)benzene derivative (a 1,6-diyne unit) with an (alkoxyethynyl)benzene (an alkoxyacetylene unit) was studied for the construction of the 2-hydroxy-3-phenyldibenzofuran skeleton of kehokorin E. Although the dimerization of the 1,6-diyne unit was a serious problem in the initial trial, installation of a bulky substituent at the terminal of the ethynyloxy group of the 1,6-diyne unit was found to inhibit the dimerization to produce cycloadducts in good yield. It was also found that the use of a 2-hydroxypropan-2-yl group as the bulky group increased the ratio of the desired 2-alkoxy-3-phenyldibenzofuran isomer to a 3-alkoxy-2-phenyldibenzofuran isomer.