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Published online: 28th April, 2016

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13464
Synthesis and Antileukemic Activity of New Fluorinated 5-Aza-9-deazapurines

Felicia Phei Lin Lim, Koon Kee Kow, Eng Hwa Yeo, Sek Chuen Chow, and Anton V. Dolzhenko*

*School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Subang Jaya, Selangor 47500, Malaysia

Abstract

Novel fluorinated 4-benzylamino-7-phenylpyrazolo[1,5-a]- [1,3,5]triazin-2-amines were prepared using an efficient and practical approach. The chemoselectivity of condensation of pyrazolylguanidine and trichloroacetonitrile was found to be solvent-dependent and, when conducted in toluene, this reaction afforded 7-phenyl-4-trichloromethylpyrazolo[1,5-a]- [1,3,5]triazin-2-amine as the main product. This key intermediate underwent nucleophilic replacement of the trichloromethyl group with fluorinated benzylamines providing a series of the target compounds. Antiproliferative activity of the prepared compounds against Jurkat T cells was explored using MTS assay. Morphological changes observed in cells treated by the most potent compounds of this series, suggested that these compounds induced apoptosis in cells.

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Published online: 28th April, 2016

Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13477
Efficient One-Pot Synthesis of Benzo[e]pyrazolo[1,5-c][1,3]thiazine Derivatives under Copper-Catalyzed Conditions

Jiyang Jie, Haoyi Li, Meihui Piao, and Xiaobo Yang*

*College of Chemistry & Chemical Engineering, Shenyang Normal University, 253 Huanghe North Street Shenyang, China

Abstract

An efficient method has been developed for the synthesis of benzo[e]pyrazolo[1,5-c][1,3]thiazines via one-pot two-step reactions of readily available substituted 1-(2-halophenyl)-3-akylprop-2-yn-1-ones, hydrazine hydrochloride and β-oxodithioesters under mild conditions, and the corresponding benzo[e]pyrazolo[1,5-c][1,3]thiazines were obtained in good to excellent yields. The novel method affords a new strategy for the construction of diverse and useful poly N,S-heterocyclic compounds.

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Published online: 27th April, 2016

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13465
A One-Pot Synthesis of Phaitanthrin E Through Intermolecular Condensation/Intramolecular Aryl C-H Amination Cascade

Tomoki Itoh, Takumi Abe, Tominari Choshi, Takashi Nishiyama, and Minoru Ishikura*

*School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

A one-pot synthesis of phaitanthrin E starting from methyl indole-3-carboxylate and isatoic anhydride through intermolecular condensation/intramolecular aryl C-H amination cascade was developed.

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Published online: 26th April, 2016

Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13458
Selective Synthesis of Monosubstituted p-tert-Butylthiacalix[4]arene under Phase Transfer Catalysis

Omran A. Omran*

*Medical laboratory department, College of Science, Majmaah University, Zulfi, 1712, 11932, Saudi Arabia
Chemistry Department, Faculty of Science, Sohag University, Sohag, 82524, Egypt

Abstract

Phase transfer catalysis (PTC) technique for lower rim alkylation of p-tert-butylthiacalix[4]arene (TCA) with diethyl bromomalonate, phenacyl bromide, N,N-diethylchloroacetamide, ethyl bromoacetate and chloroacetonitrile using K2CO3, CsOH or Na2CO3 as a base and tetraethylammonium bromide (TEAB) as catalyst in benzene has been employed. Selective synthesis of monosubstituted p-tert-butylthiacalixarene using K2CO3 or CsOH as base has been elaborated. Unprecedented alkylation cyclization as well as arene oxidation by using of Na2CO3 as a base for alkylation of p-tert-butylthiacalix[4]arene under PTC conditions led to the synthesis of two new p-tert-butylthiacalix[4]arene derivatives with heterocyclic bridging rings. The structures of the newly synthesized compounds were characterized by different spectroscopy methods IR, 1H NMR, 13C NMR, and single crystal X-ray diffraction.

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Published online: 18th April, 2016

Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13442
A Biomimetic Approach to the Synthesis of Terpene-Amino Acid Conjugates. The Ugi Reaction in the Hypothetical Biosynthesis of Marine Natural Products

Yoshiyasu Ichikawa,* Kenta Saito, Rika Mimura, Ayumi Kitamori, Akihito Matsukawa, Akifumi Ikeda, Toshiya Masuda, Hiyoshizo Kotsuki, and Keiji Nakano

*Faculty of Science, Kochi University, 2-5-1, Akebono-cho, Kochi 780-8520, Japan

Abstract

A unique pathway for the biosynthesis of the marine sponge terpenes, exigurin and boneratamides A–C, is proposed. Based on this proposal, a biomimetic strategy on key Ugi coupling reactions between terpene isocyanides and amino acids was developed for construction of the core structures of exigurin and boneratamides A–C.

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Published online: 14th April, 2016

Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13445
An Efficient Route for Synthesis and Reactions of Seleno-[2, 3-c]coumarin

Shams H. Abdel-Hafez,* Ahmed Elkhateeb, Adel A. Gobouri, Islam H. El Azab, and Gilbert Kirsch

*Department of Chemistry, Faculty of Science, Taif University, Taif-Al-Haweiah 888/21974, Saudi Arabia

Abstract

Synthesis of new selenium-containing coumarin moiety via the reaction of 4-chloro-2-oxo-2H-chromene-3-carbonitrile with selenium and sodium borohydride gave 3-Cyano-4-coumarinselenol which reacted with different halo-acids, such as chloroacetonitrile, ethyl chloroacetate and chloroacetamide to give the corresponding 3-amino-4-oxo-4H-seleno[3,2-c]chromene-2- derivatives. Hydrazonolysis of the obtained new ethyl 3-amino-4-oxo-4H-seleno[3,2-c] chromene-2-carboxylate afforded the corresponding hydrazino compound. The hydrazino compound was used as a versatile precursor for synthesis of new other heterocyclic compounds containing selenocoumarin moiety. The newly synthesized compounds were characterized using the spectroscopic tools (IR, 1H NMR, 13C NMR and mass spectroscopy) as well as microanalysis.

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Published online: 8th April, 2016

Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13430
1-Methylimidazolium Trifluoroacetate Efficiently Catalyzed Three Component Synthesis of Diazaspiro[5.5]undecane-1,5,9-trione Derivatives under Solvent-Free Conditions

Zhaohui Xu,* Houfu Zhang, Chunhua Lin, and Deyong Liu

*College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330027, China

Abstract

A simple, green and efficient method for the synthesis of 2,4-dioxa- 8,10-diazaspiro[5.5]undecane-1,5,9-trione derivatives has been developed by the reaction of aromatic aldehydes with urea and 1,3-dioxane-4,6-dione catalyzed by 1-methylimidazolium trifluoroacetate under solvent-free conditions.

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Published online: 8th April, 2016

Review | Regular issue | Prepress
DOI: 10.3987/REV-16-841
Latest Development on the Methods of Synthesizing Ionic Liquids

Xiaoxia Xie, Lihua Li, Xian Wu, Cheng Ma, and Jinsheng Zhang*

*Department of Chemical Engineering and Environment Engineering, College of Chemistry, Liaoning Shihua University, Fu Shun, Liaoning Province, 113000, China

Abstract

Nowadays, in spite that the application of ionic liquids in some domains is still at infancy stage, the related synthetic technologies have got tremendous development over one century. In this paper, we made an overview on characteristics of five approaches to synthesize ionic liquids and compared the advantages and disadvantages of different methods, and gave recommendations for the best means of synthesizing to the objectives of related studies. Finally, the present work provides a full-scale literature review of the implementation of synthesizing ionic liquids, which could assist the corporations or individuals to search for the most suitable methods and lay the foundation for exploiting more ideal methods to obtain high purity and better yields of ionic liquids in the future.

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Published online: 8th April, 2016

Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13450
Synthesis of 1-Aroyl-1,2-dihydro-3H-indol-3-ones via Cyclization of N-[2-(2-Chloroacetyl)phenyl]benzamides with Triethylamine in the Presence of Di-tert-butyl Dicarbonate

Kazuhiro Kobayashi,* Daiki Kado, and Kohei Nishikawa

*Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

1-Aroyl-1,2-dihydro-3H-indol-3-ones can now be conveniently obtained from 2-aryl-4-(Z)-(chloromethylidene)-4H-3,1-benzoxazines using an easy operated three-step sequence under mild conditions. Thus, the starting materials are hydrolyzed with dilute hydrochloric acid at 0 ˚C to N-[2-(2-chloroacetyl)phenyl]benzamides, of which treatment with triethylamine in the presence of di-tert-butyl dicarbonate at room temperature, followed by deprotection with trifluoroacetic acid at room temperature, provides the desired products.

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Published online: 8th April, 2016

Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13451
Synthesis and Antimicrobial Evaluations of Novel Spiro Cyclic 2-Oxindole Derivatives of N-(1H-Pyrazol-5-Yl)-Hexahydroquinoline Derivatives

Said Ahmed Soliman Ghozlan, Muhammed Ali Ramadan, Amr Mohamed Abdelmoniem,* and Ismail Abdelshafy Abdelhamid*

*Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Abstract

A novel series of interesting spiro cyclic 2-oxindole derivatives of N-(1H-pyrazol-5-yl)hexahydroquinoline derivatives were prepared via the versatile readily accessible cyclic β-enaminones incorporating pyrazole. Antimicrobial evaluations were performed on the prepared compounds. Most of these compounds exhibited high to moderate antimicrobial activity.

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Published online: 5th April, 2016

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13452
Concise Synthesis and Biological Evaluation of Chalcone Derivatives Bearing N-Heterocyclic Moieties

Zewei Mao, Xi Zheng, Yuping Lin, Yan Qi, Chunyan Hu, Chunping Wan,* and Gaoxiong Rao*

*Central laboratory, The NO.1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, 650021, China

Abstract

In this study, we designed and synthesized a series of chalcone derivatives bearing N- heterocyclic moieties, and screened in vitro anti- inflammatory in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and anticancer activity against a panel of human tumor cell lines. The results indicated that compound 9 not only had inhibitory effect on the generation of NO (IC50=8.11μM) and significantly inhibited the production of TNF-α, but also showed better anticancer activity against Hela and SGC7901 (IC50=1.05μM and 6.47μM, respectively), which was identified as the most potent anti-inflammatory and anticancer agent.

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Published online: 5th April, 2016

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13453
Synthesis and Antibacterial Evaluation of Some New 5-Substituted Hydantoins and Novel Twin-Drug Type Derivatives

Makoto Furutachi, Fumiko Fujisaki, Reika Tsuru, Ayumi Ejima, Toshiaki Gondo, Saho Goto, Miki Ito, Maki Nakamura, Hatsumi Aki, Nobuhiro Kashige, Fumio Miake, 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 new oxygen analogues 2 of twin-drug type bivalent mid-size lead molecule 1 and related single-drug type hydantoin derivatives 3. The new twin-drug type oxygen analogues (2a and 2b) also showed significant antibacterial activity against a Gram-positive strain (S. aureus). A comparison of the two types of twin-drug type mid-size compounds 1 and 2 showed that the original lead 1 had a higher level of antibacterial activity against a Gram-positive strain (S. aureus) than those of the compounds (2a and 2b). We also report the results of antibacterial evaluation of prepared compounds and the investigated structure-activity relationships of these molecules.

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Published online: 1st April, 2016

Short Paper | Regular issue | Prepress
DOI: 10.3987/COM-16-13439
Furan-2-carboxylic Acids from the Leaves of Nicotiana tabacum and Their Anti-Tobacco Mosaic Virus Activities

Chun-Bo Liu, Xin-Meng Xu, Qin-Peng Shen, Wei Zhang, Xiao-Feng Shen, Ye-Kun Yang, Feng-Mei Zhang, Pei He, Xiao-Xi Si, Ya-Dong Guo, Jian-Jun Xia,* and Guang-Yu Yang*

*Key Laboratory of Tobacco Chemistry of Yunnan Province, China Tobacco Yunnan Industry Company, Hongjin Road 181#, Kunming, 650231, China

Abstract

Three new furan-2-carboxylic acids, 5-(4-hydroxy-2-methoxy-6-methyl- phenyl)-3-methylfuran-2-carboxylic acid (1), methyl 5-(4-hydroxy-2-methoxy-6- methylphenyl)-3-methylfuran-2-carboxylate (2), and 5-(3-hydroxy-4-methoxy-5- methylphenyl)-3-methylfuran-2-carboxylic acid (3), together with two known furan-2-carboxylic acids (4 and 5) were isolated from the leaves of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-5 were tested for their anti-TMV activities. The results showed that compounds 3 and 4 exhibited high anti-TMV activities with inhibition rates of 29.8 and 30.3%. These rates are close to that of positive control. The other compounds also showed potential activities with inhibition rates in the range of 22.8%~25.4%, respectively.

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Published online: 22nd March, 2016

Review | Regular issue | Prepress
DOI: 10.3987/REV-16-840
Diverse and Important Contributions by Medicinal Chemists to the Development of Pharmaceuticals: An Example of Active Vitamin D3 Analog, Eldecalcitol

Noboru Kubodera*

*International Institute of Active Vitamin D Analogs, 35-6, Sankeidai, Mishima, Shizuoka 411-0017, Japan

Abstract

Presented herein are diverse and important contributions by medicinal chemists to different stages of pharmaceutical development. The conceptual elements reviewed, which are intended for young chemists who engage in drug discovery research, draw upon the author’s experience in developing eldecalcitol, an active vitamin D3 analog used to treat osteoporosis. The review covers exploratory research for a lead candidate compound; process development for practical manufacturing; and synthesis of other compounds relevant to the program, such as tritiated compounds, postulated metabolites, and miscellaneous analogs for mode of action studies.

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Published online: 1st February, 2016

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)48
Synthetic Studies toward Concavine: Synthesis of The BCD Ring Syste

Yosuke Komori, Akitoshi Kozen, and Masahiro Toyota*

*Team TOYOTA, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuencho, Sakai, Osaka 593-8531, Japan

Abstract

The BCD ring system of concavine is realized stereoselectively using a palladium-catalyzed cycloalkenylation to synthesize the CD ring and an intramolecular aza-Michael reaction to append the third ring.

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Published online: 12th January, 2016

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)26
Antiproliferative Activity of Hybrid Compounds Between 6-Methoxy-3-(4-Methoxyphenyl)-1H-Indole and 3-Phenylpiperidine Against HCT-116 and HL-60 Cells

Noriyuki Hatae,* Takashi Nishiyama, Shoko Tamura, Ryohei Yamamoto, Ayaka Matsui, Hiroki Shinchi, Satoshi Hibino, Chiaki Okada, Teruki Yoshimura, Tominari Choshi, and Eiko Toyota*

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

Indole derivatives have been potential anticancer drugs. Methyl 6-methoxy-3-(4-methoxyphenyl)-1H-indole-2-carboxylate, in particular, was reported as a potent antiproliferative agent against MCF-7, NCI-H460, and A375-C5 tumor cells. In this study, the 3-arylindole-2-carboxylate exhibited weak activity against HCT-116 colon tumor and HL-60 promyelocytic leukemia cells. To develop the potent antiproliferative indole derivatives against HCT-116 and HL-60 cells, we synthesized 6-methoxy-3-(4-methoxyphenyl)-1H-indoles with various 2-substituents and assessed their activity. The 4-phenylpiperidine derivatives attenuated the tumor cells viability. Furthermore, their calculated structure resembled that of the antiproliferative loperamide derivatives.

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Published online: 7th January, 2016

Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)46
Chemistry of Polyhalogenated Nitrobutadienes, 15: Synthesis of Novel 4-Nitro-3-amino-1H-pyrazole-5-carbaldehydes and Pyrazolo[3,4-f]indazole-4,8-diones

Viktor A. Zapol'skii, Jan C. Namyslo, Mimoza Gjikaj, and Dieter E. Kaufmann*

*Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany

Abstract

Condensation of 1-amino-1-(1H-benzo[d][1,2,3]triazol-1-yl)-3,4,4-trichloro-2-nitrobuta-1,3-dienes 3a-e with methylhydrazine leads to a series of uniquely persubstituted 4nitropyrazoles 4a-e bearing a dichloromethyl substituent in 5-position. Subsequent hydrolysis of this group applying aqueous sulfuric acid then gives interesting push-pull – substituted pyrazole-5-carbaldehydes 5a-e. Upon hydrolysis of 4a-e at harsher reaction conditions different pyrazolo[3,4-f]indazole-4,8-diones were also formed. A mechanism of the homo-condensation of carbaldehydes 5a,d to the indazole derivatives 8-13 is proposed, and as an example the structure of 3,7-bis(dimethylamino)-1,6-dimethylpyrazolo[3,4-f]indazole-4,8(1H,6H)-dione (9) has been confirmed by X-ray analysis.

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Published online: 6th January, 2016

Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)42
Formal Total Synthesis of Artocarpin

Isao Mizota, Kana Taniguchi, and Makoto Shimizu*

*Department of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Kurimamachiya-cho Tsu, Mie 514-8507, Japan

Abstract

A formal total synthesis of artocarpin was achieved via selective demethylation, iodination, followed by Suzuki-Miyaura coupling reaction of the key flavone derivative. It took only 7 steps in the overall yield of 55% starting from commercially available 3,5-dimethoxyphenol.

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Published online: 3rd December, 2015

Communication | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)54
Unexpected Highly Chemoselective Nucleophilic Substitution Reaction of 4-Dimethylamino-2-methoxy-3-trifluoroacetylquinoline with Various Nucleophiles

Etsuji Okada,* Mizuki Hatakenaka, Yoshinori Takezawa, and Keisuke Iwakuni

*Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

Aromatic nucleophilic substitution reaction of 4-dimethyl- amino-2-methoxy-3-trifluoroacetylquinoline with various nucleophiles (NuH) such as amines, thiols, and alcohols proceeded chemoselectively to give the corresponding Me2N-Nu exchanged products, 2-methoxy-3-trifluoroacetyl- 4-quinolylamines, sulfides, and ethers without any formation of MeO-Nu exchanged products in spite of the common knowledge that alkoxy group is the better leaving group than amino group.

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Published online: 1st December, 2015

Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)55
Synthesis of 7,7′-Linked-bis-indoles via 7-Tryptamines

Hakan Kandemir, Ibrahim F. Sengul, Christopher R. Gardner, Eryn L. Werry, Melissa L. Barron, Michael Kassiou, Naresh Kumar, and David StClair Black*

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

Abstract

The synthesis of 7-tryptamines was accomplished via the reduction of 7-nitrovinylindoles which were developed by the condensation of indole-7-carbaldehydes with nitromethane and ammonium acetate. 7-Tryptamines were subsequently used for the construction of 2,3-disubstituted and 3-substituted 7,7-linked-bis-indoles.

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Published online: 27th November, 2015

Paper | Regular issue | Prepress
DOI: 10.3987/COM-15-13324
P-Stereogenic Diphosphacrowns: Facile Incorporation of Aromatic Rings

Ryosuke Kato, Hiroyuki Watanabe, Yasuhiro Morisaki,* and Yoshiki Chujo*

*Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan

Abstract

P-Stereogenic diphosphacrowns containing naphthalene and pyridine rings were synthesized. Facile incorporation of aromatic rings, and chains of different lengths, into the diphosphacrown skeleton was achieved by altering the electrophile in our previously reported synthetic method. Pyridine-containing diphosphacrown exhibited chiral recognition ability for chiral ammonium salts and carboxylic acids. This is the first example of chiral recognition using P-stereogenic diphosphacrowns. 1H and 31P NMR spectra indicated that the nitrogen, oxygen, and chiral phosphorus atoms contributed to the chiral recognition cooperatively.

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Published online: 17th November, 2015

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)63
Synthesis of Noroxymorphone By N-Demethylation/ Intramolecular Acylation of Oxymorphone Catalyzed By Iron(II) Chloride

Mary Ann A. Endoma-Arias, Ales Machara, D. Phillip Cox, and Tomas Hudlicky*

*Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way St. Catharines, Ontario, L2R 3K4, Canada

Abstract

Oxymorphone was converted to its 3,14-diacetate and subjected to Fe(II)/t-BuOOH-catalyzed N-demethylation that occurred with concomitant acyl migration from the C-14 hydroxyl to the N-17 nitrogen. The resulting diacetyl compound was hydrolyzed in dilute sulfuric acid to noroxymorphone in good yield.

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Published online: 4th November, 2015

Communication | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)61
Natural Product Inspired Enantioselective Synthesis of Hexahydro-Aza-Pentalenones

Pierre-Yves Dakas, Herbert Waldmann, and Kamal Kumar*

*Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Str. 11 44227, Germany

Abstract

An asymmetric synthesis of structurally complex hexahydro-aza-pentalenones embodying four consecutive stereogenic centers including two quaternary centers, one of which is an all-carbon-quaternary center, was developed with an enantioselective [3+2] cycloaddition reaction of azomethine ylides and substituted cyclopentenones.

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Published online: 30th October, 2015

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)53
Practical Synthesis of Tricyclic Lactam Model of Antitumor Renieramycin-Saframycin Natural Products

Masashi Yokoya, Akiya Fujino, Ayako Yaguchi, Miku Yamazaki, and Naoki Saito*

*Department of Medicinal Chemistry, Pharmaceutical Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A practical synthesis of the tricyclic lactam model compound of antitumor renieramycin-saframycin natural product starting from 2-hydroxy-4,5-dimethoxy-3-methylbenzaldehyde in eleven steps was described. A tosyl group was used for protection of a phenol during this transformation. The overall yield of the target compound was 23%.

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Published online: 30th October, 2015

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)32
Unsymmetrical Phthalocyanines With One TTF unit and Octylthio or Octylsulfonyl Groups: Their Optical and Electrochemical Properties

Takeshi Kimura,* Jasmin Kang, and Shidsuko Nakajo

*Center for Instrumental Analysis, Iwate University, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan

Abstract

Unsymmetrical phthalocyanines fused with a TTF unit and six octylthio or six octylsulfonyl groups were prepared by the reaction of a mixture of phthalonitrile fused with a TTF unit and 4,5-di(octylthio)- or 4,5-di(octyl- sulfonyl)phthalonitrile. The optical and electrochemical properties of the products were determined by UV-vis absorption spectra, cyclic voltammetry, and ESR spectra.

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Published online: 30th October, 2015

Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)45
New Synthesis of Antitumor Drug Cabozantinib

Gerhard Laus, Erwin Schreiner, Sven Nerdinger,* Volker Kahlenberg, Klaus Wurst, Stefan Vergeiner, and Herwig Schottenberger

*Sandoz GmbH, Biochemiestrasse 10, 6250 Kundl , Austria

Abstract

The heterocyclic antitumor drug cabozantinib was synthesized by condensation of 4-(6,7-dimethoxyquinolin-4-yloxy)aniline and methyl 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylate in the presence of two equivalents of sodium methoxide and azeotropic removal of methanol. In turn, the key intermediate methyl 1-(4-fluorophenylcarbamoyl)cyclopropanecarboxylate was prepared from 4-fluoroaniline and dimethyl 1,1-cyclopropanedicarboxylate in the presence of one equivalent of sodium methoxide. Four crystal structures of intermediates and a byproduct were determined.

Supporting Info. (156KB)PDF (4.7MB)

Published online: 29th October, 2015

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)13
Chemical Reactivity and Application of 4-Alkylidene-3H-pyrazol-3-ones: Synthesis and Antifungal Activity of Polysubstituted Pyrazoles

Hiroshi Maruoka,* Masataka Hokao, Nobuhiro Kashige, Eiichi Masumoto, Fumi Okabe, Reiko Tanaka, Fumio Miake, Toshihiro Fujioka, and Kenji Yamagata

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

Abstract

Chemical reactivity and application of 4-alkylidene-3H-pyrazol-3-ones are described. Furthermore, twelve of the newly synthesized O-substituted pyrazoles were evaluated for their antifungal activity in vitro against Candida albicans and Saccharomyces cerevisiae.

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Published online: 26th October, 2015

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)33
Ring-contractive and -Closing Skeletal Rearrangement of 1,1’-Binaphthalene-2,2’-Diamines (Binams) Induced by An Iodine-Containing Oxidant: Synthesis of Spiro[Benzo[e]Indole-1,1'- inden]-2-Amines and Application to An Aiee-active Bf2 Complex

Masato Okazaki, Kosuke Takahashi, Youhei Takeda, and Satoshi Minakata*

*Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

Abstract

An iodine-containing oxidant-induced ring-contractive and -closing skeletal rearrangement of 1,1’-binaphthalene-2,2’-diamines (BINAMs) to afford spiro[benzo[e]indole-1,1'-inden]-2-amines has been discovered. Furthermore, a spiro product was successfully transformed into a novel luminescent spirocyclic BF2 complex.

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Published online: 23rd October, 2015

Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)56
Synthesis of 2,3,9,10-Tetraoxygenated Benzo[c]phenanthridine Derivatives via Palladium-Mediated Aryl-Aryl Coupling Reaction

Hitoshi Abe,* Naoko Kobayashi, Yutaka Kadoshima, Yasuo Takeuchi, Takashi Harayama, and Yoshikazu Horino

*Department of Environmental Applied Chemistry, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

Two 2,3,9,10-tetraoxygenated benzo[c]phenanthridine alkaloids, 1 and 2, originally reported as zanthoxyline and broussonpapyrine, respectively, were synthesized using the Pd-mediated intramolecular aryl-aryl coupling reaction as the key step.

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Published online: 23rd October, 2015

Paper | Special issue | Prepress
DOI: 10.3987/COM-15-S(T)25
Synthesis of Chemical-Biology Tools Enabling in Vivo Imaging and Analysis of Epigallocatechin Gallate

Tomohiro Asakawa,* Atsushi Yoshida, Yasuo Hirooka, Takashi Suzuki, Kunihiko Itoh, Kosuke Shimizu, Naoto Oku, Takumi Furuta, Toshiyuki Wakimoto, Makoto Inai, and Toshiyuki Kan

*Synthetic Organic & Medicinal Chemistry, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka 422-8526, Japan

Abstract

(–)-Epigallocatechin gallate (EGCg) has multiple bioactivities, and imaging/analytical tools are required for drug development studies. Here we present full details of our synthetic studies aimed at providing building blocks for development of such tools, including a concise synthesis of model compound 5,7-dideoxyEGCg (DOEGCg, 2) and an asymmetric synthesis of 6-(5-aminopentyl)-5,7-deoxyepigallocatechin gallate (APDOEGCg, 4), which contains a reactive terminal amino group. To demonstrate its utility, APDOEGCg (4) was efficiently converted to a fluorescent probe 53 by linking it to a fluorescein derivative, Tokyo Green, via the amino group. We confirmed that 53 is suitable for in vivo imaging studies. We also prepared an immunogen 56 by conjugation of 4 to human serum albumin carrier protein via a glutaraldehyde linker, and we used 56 to raise anti-EGCg antiserum in mice. The fluorescent probe and antiserum should be useful tools for biochemical investigations of the localization and target sites of EGCg. APDOEGCg should also be available for developing other novel tools for biochemical studies of catechins.

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