HETEROCYCLES

Published online: 14th July, 2020

■ Improved Synthesis of Cyclohexane-Backbone Iridium-Complexes of Quinoline-Phosphine and Their Applications in Asymmetric Hydrogenation

Qibin Liu*

*R&D department, Dalian Allychem Co. Ltd, No 5 of Jinbin Road, Jinzhou New District 116620, China

Abstract

The iridium-complexes 3 and 4 with cyclohexane-backbone derived from quinoline were easily synthesized. The key step is cis/trans stereoselective reduction of 2-(quinolin-2-yl)cyclohexanone 5 to trans-2-(quinolin-2-yl)cyclohexanol 6 using Al(Oi-Pr)3/i-PrOH and the following diastereomeric optical resolution of racemic 6 using 0.50 equiv (S)-mandelic acid in EtOAc. These complexes were used in the asymmetric hydrogenation of (E)-1,2-diphenylpropene with up to 13% ee/48% conv. using 3 and 35% ee/9% conv. using 4. For the hydrogenation of (2H-chromen-3-yl)methanol, up to 80% ee/95% yield and 72% ee/96% yield were achieved. The same configuration of the products by using 3 and 4 suggested that the absolute configuration was controlled by the configuration of the stereogenic quinolinyl-bearing carbon of the complexes.

Published online: 14th July, 2020

■ Reactivity of the Enamine Tautomer of a Cyclic 1,4-Diazadiene with a Diketone

Kazuhide Nakahara,* Koki Yamaguchi, and Hisao Kansui

*Department of Integrative Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan

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: 8th July, 2020

■ Synthetic Approach for Building Heteroannulated Furo[3,2-g]chromenes Using 4,9-Dimethoxy-5-oxo-5H-furo[3,2-g]chromene-6-carbonitrile and Cyclic Carbon Nucleophiles

Magdy A. Ibrahim,* Sami A. Al-Harbi, and Esam S. Allehyani

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo 11711, Egypt

Abstract

A novel series of polyfused heterocyclic systems containing furo[3,2-g]chromenes were efficiently synthesized. The reactivity of 4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromene-6-carbonitrile (1) was studied towards a variety of carbon nucleophilic reagents such as heterocyclic enols, heterocyclic enamines and cyclic active methylene compounds. Treatment of carbonitrile 1 with 4-hydroxycoumarin, 4-hydroxy-1-methylquinolin-2(1H)-one (3), 2-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one (4) afforded furodichromenopyridine 2, furochromenonaphthyridine 5, furochromenodipyridopyrimidine 6. Reaction of carbonitrile 1 with 4(6)-aminouracil and 5-amino-3-methyl-1H-pyrazole proceed through ring opening followed by cycloaddition into the nitrile group giving pyrido[2,3-d]pyrimidine 7 and pyrazolo[3,4-b]pyridine 8. Also, reaction of carbonitrile 1 with 5-amino-2,4-dihydro-3H-pyrazol-3-one (9), 2-(phenylimino)-1,3-thiazolidin-4- one (11), thiobarbituric acid and cyclohexane-1,3-dione produced the novel annulated furo[3,2-g]chromenes 10, 12-14, respectively. Cyclohexane-1,2-dione reacted with carbonitrile 1 in 1:2 molar ratio afforded bis-(furochromeno)[1,10]phenanthroline 15. The prepared compounds were screened in vitro for their antimicrobial activity and some of them appeared notable activity against the tested microorganisms.

Published online: 6th July, 2020

■ Facile Preparation of 3,4-Benzocoumarins from 2-Arylbenzoic Acids with NCS and Nai

Momoko Nakamura and Hideo Togo*

*Graduate School of Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

Treatment of 2-arylbenzoic acids with N-chlorosuccinimide (NCS) and NaI at 70 °C under fluorescent lighting condition gave the corresponding 3,4-benzocoumarins in good yields under transition-metal-free condition. It was found that the reactivity of NCS with NaI for the formation of 3,4-benzocoumarins from 2-arylbenzoic acids was as high as that with NIS. Thus, the formation of carboxyl radicals and their cyclization onto an aromatic ring from 2-arylbenzoic acids with much less expensive NCS and NaI, than NIS could be successfully carried out to form 3,4-benzocoumarins.

Published online: 6th July, 2020

■ Rumphellolide K, A Novel C-3/8 Ether Linkage Caryophyllane from Rumphella Antipathes

Hsu-Ming Chung, Yu-Ming Chang, Wei-Hsien Wang, Jih-Jung Chen, Tsong-Long Hwang,* and Ping-Jyun Sung*

*National Museum of Marine Biology and Aquarium, Pingtung 944401, Taiwan

Abstract

Chemical examination of Rumphella antipathes, collected in the waters of Taiwan, led to the isolation of a novel caryophyllane sesquiterpenoid, rumphellolide K (1), with a C-3/8 ether linkage. The structure of 1 was established by spectroscopic analysis and this compound displayed inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.

Published online: 3rd July, 2020

■ Efficient Synthesis of 2-Functionalized Benzoxazoles Catalyzed by Copper Iodide

Han Cao,* Xue-jing Liu,* Fu-Sheng Bie, Peng Yan, Jie Ma, Yi-Jun Shi, and Ying Han

*Engineering and Technology Research Institute of Lunan Coal Chemical,, Zaozhuang University, 1 Beian Road, China

Abstract

We reported an efficient synthesis of 2-functionalized benzoxazoles in mild condition and excellent yields. The synthetic process includes two steps. The step one contains a reaction of pendent halide formamidine derivatives and 2- aryloxyacetyl chloride generating highly selective (Z)-N-(2-halophenyl)-3-(dime- thyllamino)-2-aryloxyacrylamides, and the step two undergoes copper iodide catalyzed intramolecular C-O bond formation to yield title compounds. This strategy is not only providing newly discovered key intermediates 6a-l which contain multiple functional groups on 2-position (as building blocks), but also expanded the scope of methodologies for making diverse benzoxazoles with multiple functional groups.

Published online: 3rd July, 2020

■ Aryne-Mediated Synthesis of Oxygen Heterocycles and Application to Cysteine-Selective Trapping

Hideto Miyabe*

*Laboratory for Medicinal Chemistry, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe City, 650-8530, Japan

Abstract

The use of arynes as the highly reactive intermediates in organic synthesis has attracted substantial attention. Particularly, the introduction of ortho-(trimethylsilyl)aryl triflates as easily activatable aryne precursors led to growing activity in this field. Most reactions using these aryne precursors proceed through the addition of nucleophiles to arynes and the subsequent trapping with electrophiles to give the multisubstituted arenes with structural diversity and complexity. Based on our studies, this review highlights the insertion of arynes, generated from ortho-(trimethylsilyl)aryl triflates, into C=O π-bond of formamides. Initially, the representative examples for formal [2+2] cycloaddition of arynes with the carbon–heteroatom double bond or the heteroatom–heteroatom double bond are shown. Next, the studies on the insertion of arynes into the N−C and C=O bonds of amide group including our three-component coupling reaction leading to oxygen heterocycles are summarized. The SN2’ reaction of tricyclic oxygen heterocycles, obtained by three-component coupling reaction, was studied by using carbon and sulfur nucleophiles. The SN2’ reaction was expanded to four-component coupling reaction. Finally, the application of tricyclic oxygen heterocycles to cysteine-selective trapping is described.

Published online: 3rd July, 2020

■ Three New Benzazepine Alkaloids from Thalictrum Cirrhosum and Their Anti-Rotavirus Activity

Qiu-Fen Hu, Dian Luo, Na Lv, Ya-Ning Zhu, Lu Liu, Fan Wu, Dong Miao, Wei-Guang Wang, Qian Gao, Min Zhou,* and Guang-Yu Yang*

*Technical center, China Tobacco Yunnan Industrial Co., Ltd., Keyi Road 41#, China

Abstract

Three new benzazepine alkaloids, cirrhobenzazepines A-C (1-3), together with four known alkaloids (4-7) were isolated from the whole plants of Thalictrum cirrhosum. Their structures were elucidated by spectroscopic methods, including extensive 1H, 13C, and 2D-NMR techniques. Compounds 1-7 were tested for their anti-rotavirus activity. The results revealed that compounds 1-7 exhibited potent anti-rotavirus activity with TI valves in the range of 11.9-18.2, respectively.

Published online: 1st July, 2020

■ Reactivity of 4,6-Dimethoxy Activated Benzimidazoles

Mahiuddin Alamgir, Glenn C. Condie, Vesna Martinovic, Joanne Wood, Mohan Bhadbhade, Naresh Kumar, and David StC. Black*

*School of Chemistry, The University of New South Wales, Sydney 2052, Australia

Abstract

4,6-Dimethoxy-2-substituted-benzimidazoles undergo formylation, acylation, nitration and bromination at C7. The 7-carbaldehydes can be reduced to the corresponding hydroxymethyl compounds. Benzimidazole-2-carbaldehydes can be prepared by oxidation of 2-methyl- and 2-styryl-benzimidazoles. N-Methylation and N-allylation have also been investigated and lead to isomeric mixtures of 4,6- and 5,7-dimethoxybenzimidazoles. In general the nucleophilic capacity of the activated benzimidazoles is weaker than that of the related activated indoles, but still provides synthetic routes to a range of new heterocyclic structures.

Published online: 30th June, 2020

■ Chemical Transformations with 4,9-Dimethoxy-5-Oxo-5h- Furo[3,2-G]Chromene-6-Carbonitrile: Construction and Antimicrobial Evaluation of The Novel Heteroannulated Furochromenopyridines

Magdy A. Ibrahim,* Sami A. Al-Harbi, and Esam S. Allehyani

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo 11711, Egypt

Abstract

The chemical reactivity of 4,9-dimethoxy-5-oxo-5H-furo[3,2-g]- chromene-6-carbonitrile (1) was studied towards a variety of active methylene nitriles namely; malononitrile, cyanoacetamide, N-phenylcyanoacetamide, (phenylthio)acetonitrile, ethyl cyanoacetate and benzothiazol-2-ylacetonitrile producing the novel annulated furo[3’,2’:6,7]chromeno[2,3-b]pyridines. Reactions of carbonitrile 1 with malononitrile dimer, cyanoacetohydrazide and 1H-benzimidazol-2-ylacetonitrile showed different behavior giving the novel angular heteroannulated furochromenes 10, 11 and 13, respectively. A series of novel furo[3’’,2’’:6’,7’]chromeno[3’,2’:5,6]pyrido[2,3-d]pyrimidines were also synthesized. The proposed mechanisms for the different synthetic pathways were also discussed. The prepared compounds were screened in vitro for their antimicrobial activity and some of them showed notable activity against the tested microorganisms. Structures of the synthesized products were confirmed based on their analytical and spectral data.

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: 23rd June, 2020

■ Synthesis of Pyrrolo[2,3-C]Quinoline Alkaloid Marinoquinolines

Takashi Nishiyama, Mari Murakami, Kimiko Taninaka, Erina Hamada, Mai Endo, Daiki Kinou, Noriyuki Hatae, and Tominari Choshi*

*Graduate School of Pharmacy & Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan

Abstract

In this study, the synthesis of pyrrolo[2,3-c]quinoline as a common skeleton, is described. The process is based on the thermal electrocyclization of 3-phenylpyrrole containing isocyanate as 2-azahexatriene. Using this approach, the total synthesis of three natural marinoquinolines A, B, and E can be successfully achieved.

Published online: 18th June, 2020

■ Synthesis and Biological Evaluation of New Curcumin Analogs Inhibiting Osteoclastogenesis

Aoi Sugawara, Toshika Ohashi, Satoshi Ogawa, Naomi Goto, Mayumi Nakanishi-Matsui, Satoru Tamura, and Tomikazu Kawano*

*School of Pharmacy, Iwate Medical University, 1-1-1 Idaidori, Yahaba , Iwate, Japan

Abstract

A series of curcumin analogs (1-3) were newly designed and synthesized for the development of therapeutic agents for osteoporosis. Among the synthesized compounds, 2,5-substituted conjugated thiophene derivative (1a) and the corresponding pyrazine derivative (1c) were shown to be potential leads for the development of anti-osteoclastogenesis agent.

Published online: 11th June, 2020

■ Synthesis of Nitrogen Heterocycles through Cyanative Cyclization and Cycloaddition Reactions under Transition Metal Catalysis

Shigeru Arai* and Atsushi Nishida

*Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan

Abstract

Synthesis of cyano-functionalized nitrogen heterocycles under palladium, nickel, and cobalt catalysis is described. These transformations include the activation of C-C multiple bonds to give the functionalized pyrrolidines and their related compounds. The palladium-catalyzed reactions promote nucleophilic cyanation to non-activated terminal alkynes. Nickel catalysis enables to install H and CN functionalities into allenes with regio- and stereoselective manner. In the case of cobalt-catalyzed hydrocyanation, hydroacylation and hydroarylation, simple olefins as well as enamines are suitable substrates to construct highly functionalized hetero- and carbocycles. The applications of the above methodologies for the synthesis of alkaloids and related compounds are also described.

Published online: 9th June, 2020

■ Synthesis of Dimethoxy Activated Benzimidazoles and Bisbenzimidazoles

Mahiuddin Alamgir, Glenn C. Condie, Vesna Martinovic, Joanne Wood, Hayat Sholihin, Paul K. Bowyer, Naresh Kumar, and David StC. Black*

*School of Chemistry, The University of New South Wales, Sydney 2052, Australia

Abstract

A range of 2-substituted-4,6-dimethoxy activated benzimidazoles and 2,2'-bisbenzimidazoles have been synthesized from 2-aminoanilide derivatives under acidic conditions. The starting materials were prepared either by acylation from 3,5-dimethoxyaniline followed by nitration, or by acylation from 3,5-dimethoxy-2-nitroaniline. The 2-nitroanilides were then reduced by palladium catalyzed reaction with hydrazine and subsequent acid catalyzed cyclization giving the corresponding 4,6-dimethoxybenzimidazoles and 4,6-dimethoxy-2,2'-bisbenzimidazoles. In addition, 2-phenyl-4,5,6-trimethoxybenzimidazole has been synthesized using a similar procedure.

Published online: 5th June, 2020

■ Preparation and Acetylcholinesterase Inhibitory Activities of Pyridine-Based 1,3,4-Oxadiazole Derivatives

Xiang Yu,* Wude Yang, Ling Huang, Xingji Zhou, and Yafang Chen*

*Department of Pharmacy, Guizhou University of Traditional Chinese Medicne, , China

Abstract

Fourteen pyridine-based 1,3,4-oxadiazole derivatives were synthesized from pyridine-2-carboxaldehyde via iodine-mediated oxidative cyclisation with substituted hydrazide by using the impregnation method. Their structures were confirmed by melting point, 1H NMR, 13C NMR and HRMS. Preliminary bioassay of these derivatives' activities inhibiting acetylcholinesterase (AChE) was also evaluated in vitro at the concentration of 1 μmol/mL. The result showed that compounds 4c, 4j and 4k had moderate inhibitory activities with 52%, 59% and 59%, respectively. The preliminary structure-activity relationships revealed that the introduction of pyridine ring could enhance the activity. Molecular docking study demonstrated that compound 4k possessed an optimal docking pose with interactions at the middle of the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE.

Published online: 5th June, 2020

■ When Hydrazonoyl Chlorides Meet Terminal Alkynes: Regioselective Copper (I)-Catalysed "Click" Sequential Reactions to 5-Substituted Pyrazoles

Giorgio Molteni*

*Department of Chemistry, University of Milano, Via Golgi 19, 20133 Milano, Italy

Abstract

In the presence of catalytic amounts of copper(I) salts, terminal alkynes underwent the formation of copper(I) acetylides that enabled their nucleophilic addition onto hydrazonoyl chlorides followed by spontaneous cyclisation of the resulting alkynylhydrazone intermediate. This sequential reaction sequence was exploited as a facile and regioselective synthesis of 1,3,5-substituted pyrazoles. A catalytic cycle has been proposed accounting for the observed results.

Published online: 2nd June, 2020

■ Studies on Rotational Stability of 2-Aryl-3-(2-Fluorophenyl)Quinazolin-4-One Derivatives

Asumi Iida, Kazuya Saito, Nanami Asada, Yuuki Fujimoto, and Osamu Kitagawa*

*Department of Applied Chemistry, Faculty of Engineering, Shibaura Institute of Technology, 3-7-5 Toyosu, Kohto-ku, Tokyo 135-8548, Japan

Abstract

The rotational barriers around an N-(2-F)C6H4 bond in 2-aryl-3-(2-fluorophenyl)quinazolin-4-ones considerably lowered (ca. 4 kcal mol-1 lower) in comparison with those of 2-alkyl-3-(2-fluorophenyl)quinazolin-4-ones. The transition state structure estimated by the DFT calculation indicates that the considerable decrease in the rotational barriers in 2-aryl derivatives is caused by the alleviation of the steric repulsion between an ortho-substituent of 2-fluorophenyl group and 2-aryl group.

Published online: 22nd May, 2020

■ Chemical Syntheses and Biological Studies of Agelastatin A, A Bioactive Marine Heterocycle Gifted from Nature

Takehiko Yoshimitsu*

*Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan

Abstract

Agelastatin A, an alkaloid originally isolated from the marine sponge Agelas dendromorpha, has long been an attractive target of chemical synthesis due to its significant biological activity and unique chemical structure. The synthetic approaches to the agelastatin alkaloid have demonstrated the advances of new methodologies and strategies for accessing a highly functionalized polycyclic nitrogen heterocycle. The present article reviews synthetic endeavors on agelastatin A that have been made by various synthetic chemists as well as biological studies on the natural product and its analogues aimed at the development of medicinal resources.

Published online: 22nd May, 2020

■ 3-Trifluoromethanesulfonyloxy-4,7-Dihydro-Pyrazolo[1,5-a]Pyridine Via Ring-Closing Metathesis: Synthesis and Transformation to Withasomnine Homologs

Yoshihide Usami,* Yuya Tatsui, Kodai Sumimoto, Ayami Miyamoto, Nanase Koito, Hiroki Yoneyama, and Shinya Harusawa

*Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

3-Trifluoromethanesulfonyloxy-4,7-dihydropyrazolo[1,5-a]pyridine (9) was successfully synthesized from the starting material, pyrazole, via a sequence of reactions containing ring-closing metathesis as a key step. Suzuki-Miyaura coupling of 9 with various arylboronic acids, followed by oxidation or hydrogenation, readily afforded pyrazolo[1,5-a]pyridines (11) or 3-aryl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridines (12), respectively. Compounds 12 were found to be withasomnine homologs

Published online: 21st May, 2020

■ Synthesis of 5-H Thiazoles via Thioamide Dianions with Thioformamides: Pyridylmethyl Group on The Nitrogen Atom of Thiazole Promotes The Formation of 5-H Thiazoles

Khurnia Krisna Puji Pamungkas , Shizuka Hattori, Toshifumi Maruyama, Masahiro Ebihara, and Toshiaki Murai*

*Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University , 1-1 Yanagido, Gifu, Gifu 501-1193, Japan

Abstract

The reaction of in situ-generated thioamide dianions having a pyridylmethyl group on the nitrogen atom with thioformamides resulted in the formation of 5-H thiazoles as major products along with 5-N,N-dimethylaminothiazoles. The presence of a pyridylmethyl group plays an important role in the formation of 5-H thiazoles. A wide range of substituents at the 2-position of a thiazole ring tolerated the reaction conditions, and the intramolecular cyclization reaction proceeded smoothly. However, a phenyl substituent at the 4-position of a thiazole ring significantly reduced the yields of 5-H thiazoles.

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: 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: 12th May, 2020

■ Concise Preparation and Biological Evaluations of 9-cis-Retinoic Acid Analogues Having an Aromatic Ring

Takashi Okitsu,* Kinya Iwatsuka, Kimie Nakagawa, Toshio Okano, and Akimori Wada*

*Faculty of Pharmaceutical Science, Kobe Pharmaceutical University, 4-19-1, Motoyamakita, Higashinada, Kobe 658-8558, Japan

Abstract

A series of 9-cis-retinoic acid analogues having an aromatic ring were prepared in only two steps, and were evaluated for transcriptional activities with retinoic acid response element (RARE) and retinoid X response element (RXRE). Among them, compound 6c, bearing a 2-naphthyl substituent, exhibited the highest transcriptional activity with RXR selectivity.

Published online: 8th May, 2020

■ New and Practical Applications of Functionalized Cyclotriphosphazene Core-Based Materials

Manabu Kuroboshi* and Hideo Tanaka

*Graduate School of Natural Science and Technology, Okayama University, Tsushima-naka 3-1-1, Kita-ku, Okayama, 700-7530, Japan.

Abstract

Hexachlorocyclotriphosphazene (HCCP) is a very old compound, and used as a starring material of a variety of cyclotriphosphazene derivatives. Some of them have unique properties, and have been used in not only frame retardants but also functional materials and biomaterials. To develop cyclotriphosphazene derivatives having a desired function, numbers of substituents, regio-, and stereochemistry should be controlled in the reaction between HCCP and nucleophiles. In this review, selectivity in the reaction between HCCP and nucleophiles as well as application of the cyclotriphosphazene derivatives are summarized.

Published online: 8th May, 2020

■ Synthesis of Lactone-Fused Cyclopropanes by Ring Contractive α-Ketol Rearrangement of Ketal-Fused Cyclobutanones

Kiyosei Takasu,* Koichi Shigenaga, Kazuma Shimoda, Hiroshi Takikawa, and Yousuke Yamaoka

*Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Ring contraction of cyclic silyl ketal-fused cyclobutanones into lactone-fused cyclopropanes under desilylative conditions is described. The reaction affords 1-hydroxy- and 1-amino-1-cyclopropanecarboxylic acid derivatives from cyclobutanone substrates and their imine congeners, respectively.

Published online: 28th April, 2020

■ Thermally-Induced Doping of The Regioregular Polythiophene Bearing Alkylene Spacered Benzene Sulfonate Group at The Side Chain

Chihiro Kubota, Daisuke Morita, Keisuke Fujita, Sonoka Yamamoto, Toyoko Suzuki, Kentaro Okano, Masahiro Funahashi, Masaki Horie, and Atsunori Mori*

*Department of Chemical Science and Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

Regioregular polythiophene bearing a benzenesulfonate group, which involved an alkylene spacer between thiophene and benzene ring, was synthesized. The obtained polythiophene was shown to improve its conductivity by heating the polymer thin film through the transformation of the ester group into the corresponding sulfonic acid.

Published online: 27th April, 2020

■ Recent Advances in the Total Synthesis of Clavilactones

Akihiro Ogura and Ken-ichi Takao*

*Department of Applied Chemistry, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Japan

Abstract

Clavilactones are meroterpenoids containing a 10-membered carbocycle fused to an α,β-epoxy-γ-lactone and a hydroquinone or benzoquinone. This review describes the total synthesis of clavilactones achieved by four research groups, focusing on their innovative synthetic strategies.