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Published online: 22nd September, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)108
Synthesis and Preliminary Biological Evaluation of 2-[3-(Tetrazolyl)propyl]-1α,25-dihydroxy-19-norvitamin D3

Masashi Takano, Erika Higuchi, Kazunari Higashi, Keisuke Hirano, Akiko Takeuchi, Daisuke Sawada, and Atsushi Kittaka*

*Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Midori-ku, Sagamihara, Japan

Abstract

Four new 19-norvitamin D3 analogs, 2α-[3-(tetrazol-1-yl)propyl]-, 2β-[3-(tetrazol-1-yl)propyl]-, 2α-[3-(tetrazol-2-yl)propyl]-, and 2β-[3-(tetrazol-2-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 were synthesized. Among them, 2α-[3-(tetrazol-1-yl)propyl]-1α,25-dihydroxy-19-norvitamin D3 showed weak binding affinity for vitamin D receptor (VDR) (2.6% of 1α,25-dihydroxyvitamin D3: ca. 15% of 1α,25-dihydroxy-19-norvitamin D3) and weak VDR transactivation activity in human osteosarcoma cells, which was determined by luciferase assays (EC50 7.3 nM, when 1α,25-dihydroxyvitamin D3 0.23 nM). Although the other three compounds could not act as VDR binders by evaluation of the competition assays, 2α-[3-(tetrazol-2-yl)propyl] analog showed weak transactivation activity (EC50 12.5 nM).

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Published online: 19th September, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)39
An Efficient Domino Sonogashira/Double Carbopalladation/C–H-Activation Reaction Leading to Fluorescent Polycyclic Aromatic Hydrocarbons

Lutz F. Tietze* and Christoph Eichhorst

*Institute of Organic and Biomolecular Chemistry, University of Göttingen, Tammannstr. 2, D-37077 Göttingen, Germany

Abstract

A facile synthesis of fluorescent polycyclic aromatic hydrocarbons through a highly productive palladium-catalyzed fourfold domino Sonogashira/double carbopalladation/C–H-activation process was developed.

Supporting Info. (1.4MB)PDF (376KB)

Published online: 19th September, 2014

Communication | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)109
Synthesis and Structural Analysis of Nine-Membered Enyne Nitrogen Heterocycles

Kazunobu Igawa, Takeshi Kawabata, Kazuhiro Uehara, and Katsuhiko Tomooka*

*Institute for Materials Chemistry and Engineering (IMCE), Kyushu University, 6-1, Kasuga-koen, Kasuga, Fukuoka 816-8580, Japan

Abstract

An efficient approach to the nine-membered enyne nitrogen heterocycle 3 is presented. 1H NMR analysis reveals that both 3a (R = H, X = Ts) and 3b (R = Me, X = Ts) exhibit significant labile planar chirality in solution at ambient temperature. The X-ray analysis of 3b shows that the enantiotopic faces of the alkene are differentiated by the alkyne moiety in the solid state.

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Published online: 18th September, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)106
Toward the Pluramycins: Route Exploration from Dihydroxyanthrone Tricyclic Platform to an Aglycon, Saptomycinone B

Kei Kitamura, Yoshio Ando, Yoshihiko Maezawa, Takashi Matsumoto,* and Keisuke Suzuki*

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

Abstract

In connection with the total synthesis of the pluramycin-class antibiotics, we recently found dihydroxyanthrone derivatives to be suitable platforms for the installation of bis-C-glycosides. As a basis for the total synthesis, we explored viable routes to construct the characteristic tetracyclic skeleton. By setting saptomycinone B (5) as a model target, anthrone 6 was combined with the side chain moiety to access key intermediate 9, from which two viable routes have been developed. One of the routes has been exploited in the realization of our recent total synthesis of saptomycin B (4).

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Published online: 16th September, 2014

Communication | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)97
Regioselective Introduction of Substituents to the meso-Position of Pyrromethenone Derivative – Application to the Synthesis of Sterically Fixed Phytochrome Chromophore Anchored to the C15 meso-Position

Yudai Tanaka, Ryoji Iwamoto, Ryo Sakata, Takahiro Soeta, Kohei Endo, Shuhei Fujinami, Katsuhiko Inomata, and Yutaka Ukaji*

*Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

Pyrromethenone derivatives corresponding to the CD-ring component of phycocyanobilin chromophore were regioselectively brominated with NBS at the meso-position retaining the stereochemistry of the olefinic carbon skeleton. Subsequent introduction of carbon-substituents to the brominated pyrromethenones was accomplished by treating with Grignard reagents to afford meso-alkylated (E)-isomers regardless of the stereochemistry of the starting brominated pyrromethenones. The resulting product was applied to the synthesis of a meso-anchored sterically fixed tetrapyrrole chromophore.

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Published online: 12th September, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)107
Synthesis of the C1-C7 and C8-C18 Segments of ent-Amphidinin A

Haruaki Ishiyama, Masahiro Hangyou, Ayumi Nakatsu, Yuta Mori, and Jun'ichi Kobayashi*

*Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

A stereoselective synthesis of the C1-C7 and C8-C18 segments of the enantiomer of amphidinin A, a cytotoxic polyketide from the culture cells of a symbiotic marine dinoflagellate Amphidinium sp. (strain Y-5), has been achieved, utilizing sulfone-aldehyde coupling, Sharpless asymmetric dihydroxylation, Katsuki-Sharpless asymmetric epoxidation, and Julia-Kocienski olefination.

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Published online: 11th September, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)83
Chiral Primary Amino Amide Alcohol Organocatalyst for the Asymmetric Michael Addition of 4-Hydroxycoumarin with α,β-Unsaturated Ketones

Jun Kumagai, Yoshihito Kohari, Chigusa Seki, Koji Uwai, Yuko Okuyama, Eunsang Kwon, and Hiroto Nakano*

*Department of Applied Chemistry, Graduate School of Engineering, Muroran Institute of Technology, 27-1 Mizumoto, Muroran, Hokkaido 050-8585, Japan

Abstract

Chiral primary amino amide organocatalysts were designed and synthesized as new organocatalysts for the enantioselective Michael addition of 4-hydroxycoumarin with α,β-unsaturated ketones to produce chiral warfarin (up to 56% ee with up to 92% yield).

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Published online: 11th September, 2014

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)99
Solution-Phase-Peptide Synthesis without Purification of Column Chromatography and Recrystallization by protecting Amino Acid Esters with Phosphinyl Chloride

Guanghui An, Wei Zhou, Xiaokang Xu, Yi Pan, and Guigen Li*

*Department of Chemistry & Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, U.S.A.

Abstract

Biphenyl phosphinyl chloride (Bpp-Cl) has been successfully applied for the amino acid GAP (Group-Assisted Purification) protection. The resulting N-protected amino acid esters have been readily converted into the corresponding amino acids and peptides through GAP operation. Biphalin, enkephalin derivatives and the fragments of surfaxin have also been synthesized via GAP work-up by avoiding column chromatography. The GAP protecting group (Bpp) can be recovered and can implement the former phosphonyl groups in peptide synthesis.

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Published online: 11th September, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)92
Synthesis of Pyrrolidinofullerenes via Single Electron Transfer Reaction of Aryldienamines with C60

Naohiko Ikuma,* Hiroyuki Yamamoto, Ken Kokubo, and Takumi Oshima

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

Abstract

Variously aryl-substituted pyrrolidinofullerenes were synthesized via a single electron transfer (SET) reaction of diaryldienamines with C60 and the following consecutive 1,6-hydrogen shift and the [3 + 2] cycloaddition of the generated radical ion pair. The LUMO levels of pyrrolidinofullerenes were ca. 0.1 eV higher than C60, consequently suppressing the bisadduct formation. The phenyl –substituted pyrrolidinofullerene 2a representatively exhibited the protic acid-catalyzed intramolecular Friedel–Crafts cyclization and the DDQ induced oxidative reversion into C60.

Supporting Info. (494KB)PDF (751KB)

Published online: 10th September, 2014

Communication | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)96
Efficient Preparation of a Versatile Chiral Synthon for 1,2-Diamines via the Fe(III)-Catalyzed Diastereoselective Oxidation of 2-Imidazolone and Its Application

Hirofumi Matsunaga,* Iori Eshita, Shin Ando, and Tadao Ishizuka*

*Department of Pharmaceutical Sciences, Graduate School of Life Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan

Abstract

The efficient and predominant preparation of (4S,5S)-4,5-dimethoxy-2-imidazolidinone (DMIm) was established via the Fe(III)-catalyzed diastereoselective oxidation of 1-[(1S,2R)-2-exo-alkoxyapocamphanecarbonyl]-2-imidazolone with aqueous H2O2 up to 94% d.e., both of which were easily purified by column chromatography, followed by simple and convenient conversions. The obtained N-tosyl-(4S,5S)-DMIm proved to be a versatile chiral synthon for 1,2-diamines by the synthesis of (1S,2S)-1,2-diamino-1-(4-fluorophenyl)butane derivative, whose platinum complex showed potent antitumor activity.

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Published online: 8th September, 2014

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)98
Synthesis of Intermediary P3 Phosphazenium Framework and Its Derivatization to Chiral Cationic Macrocycles Including Two P3 Phosphazenium Units with Hydrogen Bond Donor Sites

Masahiro Terada,* Kengo Goto, Takashi Ikehara, and Azusa Kondoh

*Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan

Abstract

A new synthetic route to key intermediary phosphonium possessing a P3 phosphazene framework was developed. The reaction of the obtained intermediary phosphonium with chiral diamine, (1S,2S)-1,2-diphenyl-1,2-ethanediamine, resulted in the formation of 18-membered macrocyclic bisphosphazenium, the structure of which was verified by single-crystal X-ray diffraction analysis. The macrocyclic bisphosphazenium showed potential application as a chiral anion receptor and a chiral template in asymmetric catalysis.

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Published online: 5th September, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)100
Thiazole/thiazolone-fused Cycloheptatrienyl Phosphonates: Reactions of 2H-Cyclohepta[d]thiazole-2-thione and -2-one with Phosphites

Ohki Sato* and Ikumi Suzuki

*Department of Chemistry, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570 , Japan

Abstract

2H-Cyclohepta[d]thiazole-2-thione reacted with either trimethyl or dimethyl phosphite to furnish dimethyl 2-methylthio-4H-cyclohepta[d]thiazole-4-phosphonate and the regioisomers, 6- and 8-phosphonates. In the reaction with triphenyl phosphite, the successive S-methylation by methyl iodide and hydrolysis afforded an isomeric mixture of diphenyl 4-, 6- and 8-phosponates. Treatment of the oxygen analogue, 2H-cyclohepta[d]thiazol-2-one and triphenyl/diphenyl phosphite with/without hydrolysis gave diphenyl 3,4-dihydro-2H-cyclohepta[d]thiazol-2-one-4-phosphonate and the isomeric 6- and 8-phosphonates.

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Published online: 3rd September, 2014

Communication | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)79
Simple, Selective, and Practical Synthesis of 2-Substituted 4(3H)-Quinazolinones by Yb(OTf)3-Catalyzed Condensation of 2-Aminobenzamide with Carboxamides

Tsutomu Yoshimura, Di Yuanjun, Yu Kimura, Hisatsugu Yamada, Akio Toshimitsu, and Teruyuki Kondo*

*Advanced Biomedical Engineering Research Unit, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan

Abstract

A simple, selective, and practical synthetic method of 4(3H)-quinazolinones is realized by Yb(OTf)3-catalyzed condensation of 2-aminobenzamide with carboxamides. As the reaction proceeds, NH3 and H2O were formed as byproducts; however, Yb(OTf)3 can operate as an efficient Lewis acid catalyst without deactivation.

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Published online: 3rd September, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)74
Simple Synthetic Method for 1-Hydroxyindole and Its Application to 1-Hydroxytryptophan Derivatives

Toshiya Kawasaki, Mutsuko Tabata, Kyoko Nakagawa, Kensuke Kobayashi, Atsushi Kodama, Tetsuya Kobayashi, Masakazu Hasegawa, Keiko Tanii, and Masanori Somei*

*Noto Marine Laboratory, Institute of Nature and Environmental Technology, Faculty of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, 56-7 Matsuhidai, Matsudo-shi, Chiba 270-2214, Japan

Abstract

Simple and general synthetic method for 1-hydroxy- and 1-methoxyindole is reported. Its application to the synthesis of various types of 1-hydroxy- and 1-methoxyindole derivatives is successful, especially for the synthesis of 1-hydroxytryptophan derivatives.

PDF (631KB)

Published online: 2nd September, 2014

Communication | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)65
Three-Component Coupling Reaction of Enynes, Carbonyls, and Organozinc Reagents

Yuki Ohira, Takamichi Mori, Maya Hayashi, Gen Onodera, and Masanari Kimura*

*Division of Chemistry and Materials Science, Graduate School of Engineering, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

A mixture of t-butylzinc halide and an aldehyde reacts with enyne to provide homopropargyl alcohol in a 1,2-addition manner. Under carbon dioxide at atmospheric pressure, three components (t-butylzinc halide, enyne, and carbon dioxide) combine in a 1:1:1 ratio to give allenyl carboxylic acids in a 1,4-addition manner. These products are useful for the synthesis of heterocyclic compounds such as α,β-unsaturated γ-butyrolactones.

PDF (386KB)

Published online: 29th August, 2014

Paper | Regular issue | Prepress
DOI: 10.3987/COM-14-13070
Efficient Syntheses of Fluorine-containing Pyrimido[5,4-c]quinolines and Benzo[h][1,6]naphthyridines by Condensation Reactions of 3-Trifluoro-acetylquinolin-4-amine with Aldehydes and Ketones

Etsuji Okada,* Mizuki Hatakenaka, Shiro Nakano, Takushi Sakaemura, Takashi Mori, and Terukazu Terauchi

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

Abstract

3-Trifluoroacetylquinolin-4-amine reacted easily with various aldehydes in the presence of aqueous ammonia to afford mainly trifluoromethylated pyrimido[5,4-c]quinoline derivatives in moderate to high yields. In contrast, the use of ketones instead of aldehydes under almost the same conditions, mostly gave benzo[h][1,6]naphthyridine derivatives in excellent combined yields.

PDF (148KB)

Published online: 28th August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)86
Stereoselective Construction of 1β-Azide- and 1β-Cyano-2-deoxyribose Derivatives

Hiromichi Fujioka,* Takahiro Moriya, Kazuhisa Okamoto, Yutaka Minamitsuji, Yoshifumi Ueyama, Nao Matsumoto, and Kenichi Murai

*Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita, Osaka 560-0871, Japan

Abstract

A new method has been developed for the β-selective introduction of azido and cyano groups at the anomeric position of 2-deoxyribose derivatives. This method proceeds via the formation of a collidinium salt intermediate and allows for the stereoselective construction of 1β-azido- and 1β-cyano-2-deoxy-D-ribose derivatives. 2-Deoxy-D-ribose compounds bearing an acetoxy or tert-butoxycarbonyloxy group at their anomeric position performed well as starting materials for the formation of the corresponding 1β-azide and 1β-cyanide derivatives, respectively. 1H NMR studies of the salt intermediates revealed that the nucleophilic substitution reaction of the salt intermediates proceeded in a SN2-fashion.

PDF (676KB)

Published online: 27th August, 2014

Communication | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)58
Removal of Xylylene Groups from Tetrakis(o-xylylenedithio)phthalocyanines with Toluene/Aluminum Chloride and Construction of Dithiaphosphole Rings

Takeshi Kimura* and Shiduko Nakajo

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

Abstract

Xylylene groups were removed from tetrakis(o-xylylenedithio)phthalocyanines via C-S bond cleavage by treatment with toluene and aluminum chloride. Octathiolate anions generated were reacted with dichlorophenylphosphine to produce phthalocyanines with four dithiaphosphole rings. The structures of the products were determined by NMR and FABMS. Electrochemical and optical properties of them were verified by cyclic voltammetry and UV-vis spectroscopy.

PDF (385KB)

Published online: 27th August, 2014

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)89
Synthesis of Unsymmetrical, gem-Disubstituted Bisamides

Gabriel Schäfer, Lukas Leu, and Jeffrey W. Bode*

*Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, Wolfgang-Pauli-Strasse 10, CH-8093 Zuerich, Switzerland

Abstract

The addition of Grignard reagents to isocyanates allowed for the first successful synthesis of ketone-derived unsymmetrical, gem-disubstituted bisamides. The key to success was the in situ generation of the isocyanates under mild reaction conditions via Lossen rearrangement from the corresponding hydroxamic acids.

PDF (514KB)

Published online: 27th August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)101
Synthesis, Properties and Crystal Structures of 2,7,12,17-Tetraarylporphycenes

Daiki Kuzuhara,* Haruka Nakaoka, Takuya Okabe, Naoki Aratani, and Hiroko Yamada*

*Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan

Abstract

We have synthesized 2,7,12,17-tetraarylporphycenes, which have phenyl (7a), p-trifluoromethylphenyl (7b) or p-methoxyphenyl (7c) groups, by McMurry coupling. The crystal structures revealed that 7a formed a herringbone-type arrangement, while 7b formed a slip-stacked structure with π-π stacking. The reduction potentials of these porphycenes depend on the attached aryl groups: –1.02 V (vs. ferrocene/ferrocenium cation) for 7b (Ar = p-C6H4CF3), –1.17 V for 7a (Ar = Ph) and –1.23 V for 7c (Ar = p-C6H4OMe), which are close to that of PC61BM (Ered = –1.08 V). These porphycenes, thus, are expected to behave as n-type semiconducting materials in OTFT and OPV devices.

PDF (798KB)

Published online: 25th August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)52
Preparation of (2R,4S)/(2S,4S)-4-Hydroxypipecolinic Acid Derivatives from L-(–)-Malic Acid

Shuqiang Yin, Hiroshi Taneda, Bozhi Li, Dejun Zhou, Daishiro Minato, Kenji Sugimoto, and Yuji Matsuya*

*Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan

Abstract

Synthetically important 4-hydroxypipecolinic acid derivatives were efficiently prepared from commercially available L-(–)-malic acid. The stereochemistries of the derivatives synthesized by our method were determined by coupling constant analyses with key methine protons on C2 and C4.

PDF (376KB)

Published online: 21st August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)78
[2+2+2] Cycloaddition of Sulfanylbenzene-Tethered Diynes with Alkynes for the Synthesis of Multi-Substituted Dibenzothiophene Derivatives

Yu-ki Tahara, Riku Matsubara, and Takanori Shibata*

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

Abstract

An intermolecular [2+2+2] cycloaddition of sulfanyl- and sulfonylbenzene-tethered 1,6-diynes with alkynes using rhodium catalysts gave dibenzothiophene derivatives in moderate to excellent yields. The consecutive reaction of tetraynes with an alkyne gave an axially chiral 1,1’-bi(dibenzothiophenyl) and its tetraoxide with up to excellent ee.

Supporting Info. (1.4MB)PDF (553KB)

Published online: 21st August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)71
Macrobicyclic and Macrotricyclic Derivatives of N,N’,N’’,N’’’-Tetrasubstituted Cyclen and Cyclam

Sergei M. Kobelev, Alexei D. Averin, Alexei K. Buryak, Andrei I. Vovk, Valerii P. Kukhar, Franck Denat, Roger Guilard, and Irina P. Beletskaya*

*Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991, Moscow, Russia

Abstract

N,N’N’’,N’’’-Tetrabenzyl derivatives of cyclen and cyclam possessing two bromine atoms in trans-positioned phenyl rings were introduced in the Pd-catalyzed amination reactions with oxadiamines and polyamines to provide a wide series of macrobicyclic compounds with tetrabenzyl substituted cyclen and cyclam central moieties in yields up to 31%. Macrocycles based on 1,7-dibenzylcyclen were modified with two 3-bromobenzyl substituents and introduced in the Pd-catalyzed macrocyclization with di- and trioxadiamines to afford spherically shaped macrotricyclic cryptands in yields up to 33%. An alternative approach to isomeric macrotricyclic cryptands employed Pd-catalyzed amination of di(Boc)-di(3-bromobenzyl)cyclen followed by the dialkylation of the resulting bicycle with two bromobenzyl groups and final catalytic macrocyclization step (yields up to 24%).

PDF (722KB)

Published online: 20th August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)47
Synthesis and Biological Evaluation of C-Aromataxane Derivatives as P-Glycoprotein-mediated Multi Drug Resistance Reversal Agents

Takayuki Doi,* Naoko Yamaguchi, Kosuke Ohsawa, Kazuoki Nakai, Masahito Yoshida, Kazuhiro Satake, Yuji Mitani, Hiroshi Nakagawa, Takashi Takahashi, and Toshihisa Ishikawa

*Graduate School of Pharmaceutical Science, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Abstract

Synthesis and evaluation of C-aromataxane derivatives as P-glycoprotein-mediated MDR reversal agents have been demonstrated. Several derivatives possessing N-benzoylphenylisoserine at the C2 or C14 position of the template 2a were readily synthesized and were evaluated their affinity for P-glycoprotein. Most of the synthesized derivatives exhibited much lower cytotoxicity in both KB-3-1 cells and MDR KB-G2-cells than paclitaxel (1), and it should be noted that the compound (14R)-5a exhibited high Km and Vmax/Km values, and cytotoxicity of paclitaxel (1) in MDR KB-G2 cells was significantly recovered (98% reduction, IC50 30 nM) in the presence of 5a (5.0 μM). The structural features such as endo-cage conformation and the stereochemistry at the C14 position is crucial to exhibit an excellent affinity for P-glycoprotein.

Supporting Info. (395KB)PDF (874KB)

Published online: 20th August, 2014

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)95
A Concise Approach to Tetracyclic Spiroamine Scaffold of Erythrinan Alkaloids via an Oxidative Dearomatization-Spirocyclization Sequence

Emi Saito, Akihiko Nakamura, 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

This paper describes a novel synthetic approach to 11,12-dimethoxy-8,9-dihydro-1H-indolo[7a,1-a]isoquinoline-2,6-dione, which is a key synthetic intermediate to some erythrinan alkaloids. This concise approach features an oxidative dearomatization-spirocyclization sequence mediated by phenyliodine (III) bis(trifluoroacetate) (PIFA) that efficiently forms the tetracyclic spiroamine scaffold. An unusual solvent effect in the oxidative dearomatization-spirocyclization sequence is also described.

PDF (318KB)

Published online: 20th August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)93
Total Synthesis of Maremycins A and D1 using Chiral and Cyclic Nitrone with (E)-3-Ethylidene-1-methylindolin-2-one

Tohru Ueda, Mitsuhide Inada, Nobuyoshi Morita, and Osamu Tamura*

*Laboratory of Organic Chemistry, Pharmaceutical Sciences, Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

Abstract

Total syntheses of maremycin A (4) and maremycin D1 (8) were described, featuring 1,3-dipolar cycloaddition of a chiral cyclic nitrone 15 with (E)-3-ethylidene-1-methylindolin-2-one (13). The cycloaddition was reversible, especially at high temperature in the presence of a Lewis acid or in a solvent possessing a high acceptor number. One of the cycloadducts was efficiently led to maremycin A (4) and maremycin D1 (8). High optical purity of 4 was confirmed by chiral HPLC comparison with ent-4 prepared from ent-15 and 13.

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Published online: 19th August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)43
Synthesis of Bicyclic Dioxetanes bearing a Hydroxyphenanthrene or Hydroxy[4]helicene Moiety and Their Base-induced Chemiluminescent Decomposition

Yohei Koyama, Nobuko Watanabe, Hisako K. Ijuin, and Masakatsu Matsumoto*

*Department of Chemistry, Faculty of Science, Kanagawa University, 2946 Tsuchiya, Hiratsuka 259-1293, Japan

Abstract

Six bicyclic dioxetanes bearing a 1-hydroxyphenanthren-3-yl 2-iv, 3-hydroxyphenanthren-1-yl 2-ov, 4-hydroxyphenanthren-2-yl 2-oh, 2-hydroxyphenanthren-4-yl 2-ih, 4-hydroxy[4]helicen-2-yl 3-iv and 2-hydroxy[4]helicen-4-yl group 3-ov were synthesized and their base-induced chemiluminescent decomposition was investigated in a TBAF (tetrabutylammonium fluoride) / MeCN system. For dioxetanes in the iv-series 2-iv and 3-iv including α-naphthol-analog 17a and those in the ov-series 2-ov and 3-ov including β-naphthol-analog 17b, we investigated how the chemiluminescence properties changed with an increase in the number of fused benzene rings of a hydroxyarene moiety attached to a dioxetane ring. The results showed that a) maximum wavelength of chemiluminescence λmaxCL tended to shift to a longer wavelength region as the number of fused benzene rings increased, b) the kCTID values for the iv-series were >1000 times larger than those for the ov-series regardless of the number of fused benzene rings, and c) a dioxetane in the iv-series tended to have a higher singlet-chemiexcitation efficiency ΦS than the corresponding dioxetane in the ov-series. This tendency could be explained by the “syn/anti” rotational isomerism of an aromatic electron donor, where an anti-rotamer gives ΦS far more effectively than a syn-rotamer.

Supporting Info. (3MB)PDF (713KB)

Published online: 19th August, 2014

Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)91
4,8-Dihydropyrrol[3,4-f]isoindole as a Useful Building Block for Near-Infrared Dyes

Hidemitsu Uno,* Mitsunori Nakamura, Kazuki Jodai, Shigeki Mori, and Tetsuo Okujima

*Department of Chemistry and Biology, Graduate School or Science and Engineering, Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577, Japan

Abstract

4,8-Dihydropyrrol[3,4-f]isoindole was prepared from 4,7-dihydroisoindole based on the modified Barton-Zard reaction. Addition of phenylsulfenyl chloride followed by oxidation and dehydrochlorination gave phenylsulfonyldihydroisoindole, which underwent the smooth reaction with an isocyanoacetate under basic conditions to give 4,8-dihydropyrrol[3,4-f]isoindole-1,5- and 1,7-dicarboxylates in good yields. The pyrrolisoindole was successfully converted to the benzene-fused bisBODIPY, absorption maximum of which was 758 nm.

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Published online: 19th August, 2014

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)84
Palladium-mediated Intramolecular Biaryl Coupling Reaction: Convenient Preparation of Furoquinolinone Derivatives

Hitoshi Abe,* Mayu Kamimura, Yoshinori Komatsu, and Yoshikazu Horino

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

Abstract

Furo[2,3-c] or furo[3,2-c]quinolinone derivatives were prepared via the intramolecular biaryl coupling reaction of 2-furoylanilides or 3-furoylanilides using a palladium catalyst.

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Published online: 19th August, 2014

Communication | Special issue | Prepress
DOI: 10.3987/COM-14-S(K)27
Facile Synthesis of Guaiazulene-Heterocycle Hybrids via Ugi Multicomponent Reactions

Naoko Takenaga,* Koh Fukazawa, Miki Maruko, and Koichi Sato*

*Laboratory of Medicinal Chemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan

Abstract

The Ugi reaction with isocyanoazulene 1 afforded a variety of azulene-heterocycle hybrids. The described approach could be applied to combinatorial synthesis of biologically active compounds of the azulene series.

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