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13 data found. 1 - 13 listed

Published online: 22nd January, 2020

Review | Regular issue | Prepress
DOI: 10.3987/REV-19-922
Bridged Nucleosides as Building Blocks of Oligonucleotides: Synthesis and Properties

Yoshiyuki Hari*

*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan

Abstract

Bridging between the 2ʹ- and 4ʹ-carbons in a nucleoside restricts the furanose ring to C3ʹ-endo conformation, which coincides with the sugar conformation in an oligonucleotide forming a duplex with single-stranded RNA (ssRNA) and a triplex with double-stranded DNA (dsDNA). Therefore, oligonucleotides modified by 2ʹ,4ʹ-bridged nucleosides generally increase hybridization ability with ssRNA and dsDNA when compared with the natural oligonucleotide. Till date, a large number of 2ʹ,4ʹ-bridged nucleosides with additional two-atom to four-atom bridges between 2ʹ- and 4ʹ-carbons have been developed by many research groups including our group. For this, ionic cyclization, ring-closing metathesis, and radical cyclization have been used so far as the synthetic strategies of bridge constructions. Based on such a background, we recently proposed a 2ʹ,4ʹ-bridged nucleoside possessing 6ʹ-oxygen founded on a new design concept and several types of analogs including 2ʹ-O,4ʹ-C-ethyleneoxy-bridged 5-methyluridine with a four-atom bridge have been developed. In addition, as a new strategy of bridge construction, radical cyclization using the 4ʹ-carbon radical of a nucleoside was exemplified and a promising 2ʹ,4ʹ-bridged nucleoside, the 6ʹ-methyl analog of 2ʹ-O,4ʹ-C-ethylene-bridged 5-methyluridine, was found. This review mainly focuses on our recent results on bridged nucleosides used for chemically modified oligonucleotides. It describes the design and synthesis of the bridged nucleosides, along with the properties of oligonucleotides including bridged nucleosides.

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Published online: 22nd January, 2020

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-19-14191
Synthesis and Biological Evaluation of NMDI-14 Derivatives as anti-Mesothelioma Agents

Hong Nhung Nguyen, Koya Suzuki, Yasuaki Kimura, Takatsugu Hirokawa, Yuko Murakami-Tonami, and Hiroshi Abe*

*Graduate School of Sceince, Nagoya University, Furo, Chikusa, Nagoya, Aichi 464-8602, Japan

Abstract

Mesothelioma is a severe tumor formed in pleura and peritoneum, for which no useful molecular-targeting therapy is available. We synthesized several derivatives of NMDI14, which is a reported inhibitor for non-sense mediated mRNA decay, and evaluated the activity of the NMDI14 derivatives as potential anti-mesothelioma agents. Some of the synthesized compounds showed promising activity in terms of cytotoxicity toward mesothelioma model cells and promotion of GAS5 expression selectively in mesothelioma cells. These results indicate that the NMDI14 derivatives may be useful for further developing clinically effective anti-mesothelioma drugs.

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Published online: 10th January, 2020

Review | Regular issue | Prepress
DOI: 10.3987/REV-19-919
Alkyl Pyridinesulfonates and Allylic Pyridinecarboxylates, New Boosters for The Substitution at Secondary Carbons

Yuichi Kobayashi*

*Meiji University, Organization for the Strategic Coordination of Research and Intellectual Properties, 1-1-1, Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan

Abstract

Substitution at allylic secondary carbons using the pyridinecarboxylate (picolinoxy, PyCO2, or Pic) leaving group is described in the first part of this review (Sections 2–4). Alkyl as well as less reactive alkenyl, heteroaryl, and aryl copper reagents are suitable for the substitution, giving anti SN2' products highly regio- and stereoselectively. In Section 2, finding and synthetic application of the allylic substitution giving tertiary carbon centers are presented. Extension of the substitution for the construction of quaternary carbon centers is described in Section 3 with its synthetic application. Section 4 deals with the construction of quaternary carbon centers on cyclohexane rings by the allylic substitution of cyclohexylidene picolinates. The stereochemistry is created by equatorial attack to the chair conformer with high diastereselectivity. The stereochemical prediction facilitated synthesis designs of biologically active compounds. The second part of the review (Section 5) presents recent advances in metal-catalyzed substitutions at secondary alkyl carbons, giving enantiomerically enriched products. Our findings of the pyridinesulfonyloxy leaving group and an associated copper catalyst are included. Substitutions with cuprates are mentioned briefly for reactivity discussion with the copper-catalyzed substitution.

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Published online: 8th January, 2020

Review | Regular issue | Prepress
DOI: 10.3987/REV-19-918
Synthesis of Heterocycles Utilizing N-Alkoxyimines and Amides

Motohiro Yasui, Norihiko Takeda, and Masafumi Ueda*

*Department of Medicinal Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyamakitamachi, Higashinada, Kobe 658-8558, Japan

Abstract

N-Alkoxyimines and amides are unique functional groups bearing adjacent N-O bonds. Alkynes having an N-alkoxyimine or amide group generate reactive vinyl metal species through activation by a transition metal catalyst to synthesize heterocycles. This approach, which allows various sequential reactions, can be expected to directly form a complex heterocycle from a simple starting material under mild conditions. Meanwhile, these kinds of reactions require chemoselectivity between the N- and O-atoms at the nucleophilic site and/or regioselectivity at the electrophilic alkyne moiety. This review introduces intramolecular nucleophilic addition of N-alkoxyimines/amides into an alkyne moiety, followed by various transformations to synthesize heterocycles.

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Published online: 7th January, 2020

Paper | Regular issue | Prepress
DOI: 10.3987/COM-19-14184
Synthesis, Characterization, and Electronic and Structural Calculations of Some 1,4-Disubstituted Cyclopenta[d][1,2]oxazines

Nathan C. Tice,* Steven Wild, Christian Olmstead, Edwin D. Stevens, Bangbo Yan, Hannah Brooks, and Judith L. Jenkins

*Department of Physical Sciences, The University of Findlay, 1000 North Main Street, Findlay, OH 45840, U.S.A.

Abstract

Our current work focuses upon the formation and characterization of some 1,4-disubstituted cyclopenta[d][1,2]oxazines via ring closure with hydroxyl amine on a 1,2-diacyl cyclopentadiene precursor. Recently, we formed and characterized two fused-ring disubstituted oxazines (R = thienyl, 4-chlorophenyl) in high yield, which serve as precursors towards oxazine-based conducting polymers. X-ray crystallographic analysis of the thienyl oxazine did show favorable π-π stacking, critical to effective intermolecular charge transfer. To further evaluate its electronic and optical properties, theoretical calculations were performed on the thienyl oxazine, including Natural Bond Orbital analysis. Calculated values suggest a strong potential for Non-Linear Optical applications.

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Published online: 6th January, 2020

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-19-14190
Synthetic Strategy to New Terphenyl-Type Bis-Pyrrole Arenes Starting from Highly Electron-Deficient 4-Nitroanilines with 1,4-Diketones

Hyejeong Lee, Seolhee Bae, Eungyung Kim, Jihye Park, and Byeong Hyo Kim*

*Department of Chemistry, Kwangwoon University, 447-1, Wolgye-Dong Nowon-ku, Seoul, 139-701, Korea

Abstract

A new synthetic method for converting highly electron-deficient 4-nitroanilines into terphenyl-type bis-pyrrole arene derivatives has been developed, which is not easy to accomplish using conventional methods because of their poor reactivity. This process involves an indium-mediated reductive cyclization reaction of highly electron-deficient 2,6-disubstituted nitroanilines in the presence of a 1,4-diketone to form 2,6-disubstituted 4-(1H-pyrrole-1-yl)anilines followed by cyclization with another 1,4-diketone to give the target bis-pyrrole arene products in moderate to high yield.

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Published online: 26th December, 2019

Review | Regular issue | Prepress
DOI: 10.3987/REV-19-920
Microwave-Assisted Synthesis of 1,3,5-Triazines: Efficient Approaches to Therapeutically Valuable Scaffold

Ahmad Junaid and Anton V. Dolzhenko*

*School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia

Abstract

1,3,5-Triazine ring is an important scaffold for the construction of new biologically active compounds. Microwave irradiation has found an extensive application in organic and medicinal chemistry accelerating reactions and drug discovery process. This review systematizes methods for the microwave-assisted construction of 1,3,5-triazine ring and discusses their advantages and disadvantages over methods based on the conventional heating.

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Published online: 26th December, 2019

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-19-14188
Pentenyl Coumarins from the Roots and Stems of Yunnan Local Sun Cured Tobacco and Their Bioactivity

Qiu-Fen Hu,* Dian Luo, Na Lv, Yin-Ke Li, Wei-Song Kong, Jing Li, Xin Liu, Qian Gao, Guang-Yu Yang, Hai-Ying Xiang,* and Ju-Xing Jiang*

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650031, China

Abstract

Three new (1-3), together with two known (4 and 5) pentenyl coumarins were isolated from the roots and stems of Yunnan local sun cured tobacco. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1~5 were tested for their anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity. The results revealed that compound 2 showed strong inhibition with inhibition zone diameter (IZD) of 18.6 ±2.6 mm, and compounds 1, 3, 4, and 5 showed good inhibition with IZD of 14.2±2.2, 14.8±2.3, 12.4 ±2.2, and 15.1±1.8 mm, respectively. Compounds 1-5 were also tested for the antioxidant activity, and they showed notable antioxidant activity with IC50 values of 4.92, 4.18, 4.43, 4.65, and 4.07 μg/mL, respectively

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Published online: 26th December, 2019

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-19-14193
Studies toward Identifying the Pharmacophore of L-755,807 for Amyloid-β Aggregation Inhibitory Activity

Kenichi Kobayashi,* Kosaku Tanaka III, Yusuke Honma, Momoko Suzuki, and Hiroshi Kogen*

*Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

To investigate the structure–activity relationship of L-755,807 for amyloid-β aggregation inhibitory activity, L-755,807 analogs were synthesized and biologically evaluated. The results suggest that a hydrophobic conjugated carbon chain with a terminal hydrophilic functional group is essential for the potent activity. These findings provide a starting point for identifying the pharmacophore of L-755,807.

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Published online: 23rd December, 2019

Review | Regular issue | Prepress
DOI: 10.3987/REV-19-915
Chemistry of Anti-Hiv Active Trimeric Pyranonaphthoquinone Conocurvone: Synthetic Studies towards Monomeric Teretifolione B and Related Compounds

Takuya Kumamoto* and Kazuaki Katakawa

*Department of Synthetic Organic Chemistry, School of Pharmaceutical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan

Abstract

Pyranonaphthoquinone natural products are widely distributed in plants and microorganisms and have diverse biological activities. Angular benzochromenes are a small class of natural products isolated from Conospermum and Pentas plants. Of these, conocurvone was isolated from Conospermum as a trimeric pyranonaphthoquinone that has potent anti-HIV activity. We have focused on the total synthesis of compounds that exhibit biological activity or whose activity is enhanced upon oligomerization. This review describes the discovery and biological activities of the trimeric pyranonaphthoquinone conocurvone and related compounds, as well as our and other researchers’ synthetic studies toward monomeric pyranonaphthoquinones.

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Published online: 17th December, 2019

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-19-14180
Chemoselectivity-Tunable [5 + 2] Cycloadditions of Allenamides and Oxidopyryliums

Min Yang, Liangliang Kang, and Shuzhong He*

*School of Pharmaceutical Sciences, Guizhou University, 440 Chongyi Building,Guizhou University, Huaxi District, China

Abstract

[5 + 2] Cycloadditions between allenamides and oxidopyryliums are described. A series of substituted cycloheptanones were synthesized by this method with moderate to good yields. Interestingly, the chemoselectivity of this reaction could be tuned by changing the electron-withdrawing groups on the allenamide nitrogen atom. When oxazolidinone chiral auxiliaries were introduced in the allenamide substrate, [5 + 2] cycloadducts could be obtained with high diastereoselectivities. This reaction provides a useful synthetic protocol for the construction of highly substituted seven-membered rings.

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Published online: 6th December, 2019

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-19-14181
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.

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Published online: 21st November, 2019

Review | Regular issue | Prepress
DOI: 10.3987/REV-19-917
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.

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13 data found. 1 - 13 listed