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Published online: 20th June, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)87
A Synthetic and Spectroscopic Investigation of the Asymmetric α-Lithiation-trapping of Six-Membered N-Boc Heterocycles using Alexakis Diamines

James D. Firth, Giacomo Gelardi, Peter J. Rayner, Darren Stead, and Peter O'Brien*

*Department of Chemistry, University of York, Heslington, York YO10 5DD, U.K.

Abstract

The asymmetric lithiation-trapping of six-membered N-Boc heterocycles using s-BuLi and two different Alexakis diamines is reported. These readily available ligands outperform the current ‘best-in-class’ sparteine-type diamines in the lithiation and benzophenone trapping of N-Boc piperazines and the lithiation-cyclisation-trapping of N-Boc-4-chloropiperidine. In situ IR spectroscopy has been used to optimise lithiation times and to discover previously unknown subtleties regarding the lithiation step.

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Published online: 20th June, 2018

Review | Special issue | Prepress
DOI: 10.3987/REV-18-SR(T)3
β-Amino Alcohol Organocatalysts for Asymmetric Cycloadditions

Hiroto Nakano,* Isiaka Alade Owolabi, Madhu Chennapuram, Yuko Okuyama, Eunsang Kwon, Chigusa Seki, Michio Tokiwa, and Mitsuhiro Takeshita

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

Abstract

A design of a chiral organocatalyst is very important for obtaining of a chiral product with a high optical purity in a catalytic asymmetric reaction. Recently, we developed a series of chiral β-amino alcohol organocatalysts A that showed high level of catalytic activity in some asymmetric reactions. These β-amino alcohols are stable in air, and have two advantageous features, easy preparation and exhibiting high stereoselectivity in an enantioselective reaction. This review summarizes our recent works involving the Diels-Alder (DA) reactions of 1,2-dihydropyridines, anthrones or 3-hydroxy-2-pyridones as dienes with dienophiles, the asymmetric 1,3-dipolar cycloaddition of nitrones with α,β-unsaturated aldehydes and the crossed aldol reaction of isatins with acetaldehyde, by the use of the simple primary β-amino alcohols as efficient chiral organocatalysts for the asymmetric reactions.

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Published online: 14th June, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(F)4
Efficient Synthesis of Methyl (S)-4-(1-Methylpyrrolidin-2-yl)-3-oxobutanoate as the Key Intermediate for Tropane Alkaloid Biosynthesis with Optically Active Form

Nanda Kumar Katakam, Cole W. Seifert, John D’Auria,* and Guigen Li*

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

Abstract

Methyl (S)-4-(1-methylpyrrolidin-2-yl)-3-oxobutanoate has been synthesized for enzymatic studies on cyclization enzymes during cocaine biosynthesis in Erythroxylum coca plants. During the present new synthesis, L-proline was first protected with Cbz group and reduced to chiral amino alcohol, which were then followed by Swern oxidation, Wittig reaction and decarboxylative condensation. At the last step, N-methylamino acid precursor was treated with 1,1’-carbonyldiimidazole followed by reacting with methyl potassium malonate to give the 3-oxobutanoate in 54% overall yield. This new strategy has proven to avoid obvious racemization of the L-proline chiral center during the synthesis. In addition, six of the eight synthesis steps were performed via GAP chemistry/technology without the use of column chromatography for purification

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Published online: 12th June, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)91
Preparation of meso-Silylporphyrins via Nickel-Catalyzed Coupling of meso-Brominated Ni(II) Porphyrins with Silylzinc Reagents

Satoshi Hayashi,* Taiga Endo, and Toshikatsu Takanami*

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

Abstract

In this paper, we developed a technique for the nickel-catalyzed coupling of meso-brominated Ni(II) porphyrins with silylzinc reagents in order to prepare meso-silyl-substituted Ni(II) porphyrins. Porphyrin silylation occurs under mild conditions and exhibits both excellent substrate generality and functional group compatibility.

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Published online: 12th June, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)75
Synthesis Of N- [4-(2'-[18f]Fluoroalkoxybenzoyl)]- And N-(3-[123i]Iodo-4-Methoxybenzoyl)Pyrrolidin-2-Ones As Potential Brain Imaging Agents

Murthy R. Akula, David Blevins, George W. Kabalka,* and Dustin Osborne

*Department of Chemistry, University of Tennessee, Knoxville, Tennessee, 37996-1600, U.S.A.

Abstract

The microfluidic synthesis of promising brain imaging PET agents N-[4-(2’-[18F]fluoroalkyloxybenzoyl)]pyrrolidin-2-ones 13a-c was accomplished by nucleophilic radiofluorination of the corresponding tosylate precursors 9a-c with kryptofix-potassium carbonate-[18F]fluoride. Decay corrected radiochemical yields of 35±5% (13a), 38±8% (13b) and 40±5% (13c) were obtained with radiochemical purities of ≥ 93%. The total reaction time, including HPLC purification was 40 min. N-(3-[123I]Iodo-4- methoxybenzoyl)pyrrolidin-2-one, 18, was prepared by radioiododestannylation of tin precursor 17 using Na123I and 0.3% peracetic acid in 84% radiochemical yield in 20 min.

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Published online: 8th June, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)92
Polymorphism of Macrocyclic Oligothiophehe 8-Mers

Hideyuki Shimizu, Tahmina Haque, Masataka Takashika, Hiroyuki Otani, and Masahiko Iyoda*

*Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan

Abstract

Macrocyclic oligothiophene 8-mer E,E-8T6A composed of eight thienylene, six ethynylene, and two vinylene units exhibits unique polymorphism. In the solid state, E,E-8T6A formed nanostructured polymorphs such as single crystals, fibers, long and short rods, and square tubes depending on the solvent used for crystallization. In contrast, E-8T7A with one vinylene unit and 8T8A without vinylene unit afforded single crystals, microcrystalline, and short rods in the solid state. Morphological difference between E,E-8T6A and E-8T7A/8T8A is due to the flexibility of the macroring of E,E-8T6A with two vinylene units, and the shape-persistent but rather flexible E,E-8T6A forms various polymorphs in the solid state.

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Published online: 5th June, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)93
Notable Difference between Tetrabutylammonium Fluoride and Organic Superbases as Triggers for The Chemiluminescent Decomposition of Bicyclic Dioxetanes Bearing A 4-(N-Phenylbenzimidazol-2-Yl)-3-Hydroxyphenyl Moiety

Nobuko Watanabe, Koh Kumagai, Rei Ohtuka, Ayu Wakatsuki, Hisako K. Ijuin, Yoshio Kabe, and Masakatsu Matsumoto*

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

Abstract

Chemiluminescent decomposition of bicyclic dioxetanes 3a−3c bearing a 4-(N-phenylbenzimidazol-2-yl)-3-hydroxyphenyl moiety was effectively induced by organic superbases, BTPP [(tert-butylimino)tris-(pyrrolidino)phosphorene], TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene), MTBD(7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene), DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), and TMG (tetramethylguanidine), as well as TBAF in acetonitrile. Dioxetane 3c bearing a 3,5-dihydroxyphenyl moiety showed diverse chemiluminescence profiles depending on the base used. BTPP caused chemiluminescent decomposition due to the di-oxido anion of dioxetane, while DBU and TMG induced chemiluminescence from the mono-oxido anion of dioxetane. On the other hand, TBAF caused effective chemiluminescence due to the mono-oxido anion, though it acted as a stronger base than BTPP with regard to the rate of decomposition of 3c.

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Published online: 4th June, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)85
Synthetic Studies Toward Isoschizogamine: Construction of Pentacyclic Core Structure

Kenji Sugimoto, Hiroaki Fujiwara, Akihiro Takada, Dong-Gil Kim, Hirofumi Ueda, and Hidetoshi Tokuyama*

*Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan

Abstract

Development of a concise construction of the pentacyclic core skeleton of isoschizogamine was described. Tetracyclic A,B,D,F-rings structure was assembled by intramolecular aza-Diels–Alder reaction via an ortho-iminoquinone methide intermediate. The C-ring was formed by oxidation of the benzylic position with a combination of Cr(CO)6 and t-BuO2H, followed by the introduction of an aminoethyl side chain, C–H oxidation of the lactam ring with CrO3 and n-Bu4NI, and final cyclization to construct the cyclic aminal moiety.

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Published online: 4th June, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(F)6
Synthesis and Cytotoxicity of Novel Bis-Ellipticines and Bis-Isoellipticines

Judy A. Obaza-Nutaitis and Gordon W. Gribble*

*6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, U.S.A.

Abstract

A series of bis-ellipticines 79 and bis-isoellipticines 1012 tethered through the indole nitrogen was synthesized and screened for antitumor cytotoxicity in the L-1210 murine leukemia assay. Activity was only displayed by 1,10-bis(6-ellipticinyl)-n-decane (8)

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Published online: 4th June, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(F)7
Total Synthesis of Haplacutines B and C

Noriki Kutsumura,* Keisuke Numata, Shiho Mosaki, and Takao Saito*

*Faculty of Science, Department of Chemistry, Tokyo University of Science, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan

Abstract

The total synthesis of 4-quinolone alkaloids, haplacutines B and C, has been achieved. The synthetic highlights are chemoselective construction of a 2-alkyl-4-quinolone skeleton via intramolecular base-promoted cyclocondensation of ortho-alkylamidoacetophenone and stereoselective elongation of the dienol side chain via the Stille coupling

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Published online: 1st June, 2018

Review | Special issue | Prepress
DOI: 10.3987/REV-18-SR(T)4
Cycloaddition Reactions of N-Alkyl-alpha,beta-unsaturated Imines: Facile Preparation of Azaheterocycles for Synthesis and Biological Applications

Ambara R. Pradipta, Liliya Latypova, Dilyara Chulakova, Ivan Smirnov, Almira Kurbangalieva, and Katsunori Tanaka*

*Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan

Abstract

In this review, we will describe the utilization of formal [4 + 4] cycloaddition reaction of N-alkyl-,-unsaturated imines derived from acrolein and biogenic alkylamines to synthesize 2,6,9-triazabicyclo[3.3.1]nonanes and 1,5-diazacyclooctanes. We also include here a new structural data of 1,5-diazacyclooctane determined by X-ray crystallography. Biological examination of 1,5-diazacyclooctanes revealed for the first-time its role in inhibition of amyloid- (A) 1-40 fibrillization. Eventually, we also found that when substituted or unsubstituted acrolein is reacted with chiral ethanolamine in the presence of formaldehyde, then hexahydropyrimidines or 1,3,5-triazacyclooctanes were produced in high yield and stereoselectivity through formal [4 + 2] or [4 + 2 + 2] cycloaddition reactions. Lastly, simple functional group manipulations of the cycloaddition products can be used to synthesize chiral 1,3-diamines, which could not be simply accessed by other methods.

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Published online: 31st May, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)31
Facile Synthesis of Indolelactones using Mn(III)-Based Oxidative Substitution-cyclization Reaction

Takeshi Inoue and Hiroshi Nishino*

*Department of Chemistry, Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1, Chûou-Ku, Kumamoto 860-8555, Japan

Abstract

Based on the oxidation of indole with Mn(OAc)3 in the presence of 1,1-diarylethenes affording 3-vinyl-substituted indoles, a similar oxidation using indole-2-carboxylic acids was evaluated in order to effectively introduce the substituent group to the C-3 position of the indolecarboxylic acids. The coupling reaction followed by oxidative cyclization smoothly proceeded at room temperature in an AcOH-HCO2H mixed solvent to give the desired indolelactones in high yields. The reaction details, the structure determination of the products and a brief reaction mechanism are described.

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Published online: 31st May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)80
Facile Synthesis of Stable Uracil-Iodonium(III) Salts with Various Counterions

Naoko Takenaga,* Shohei Ueda, Takumi Hayashi, Toshifumi Dohi, and Shinji Kitagaki

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

Abstract

Aryliodonium(III) salts, one of the useful and important classes of hypervalent iodine compounds, have a wide range of applicability, i.e., photoacid generator, active bactericides, and coupling agents for reacting a wide range of nucleophiles even under metal-free conditions. In this report, we present an approach to the design of stable uracil-iodonium(III) salts with various counterions. Uracil is an important substructure that exists in many biologically active compounds and the introduction of such a moiety in iodonium(III) salts would be of high utility in organic chemistry.
This paper is dedicated to Professor Kiyoshi Tomioka on the occasion of his 70th birthday.

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Published online: 30th May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)53
Design and Synthesis of A DNA-Like Structure Composed of Alkynyl C-Nucleotide with 2-Aminopyrimidin-4-one as a Nucleobase

Kurosaki Fumihiro, Junya Chiba,* and Masahiko Inouye*

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

Abstract

A heterocyclic compound, 2-aminopyrimidin-4-one, was found to be a new candidate of a non-natural nucleobase that forms a novel base pair by self-dimerization. 2-Aminopyrimidin-4-one was connected to a deoxyribose through an acetylene linkage. The non-natural nucleoside was derivatized to its phosphoramidite that could be subjected to a conventional solid-phase DNA synthesis. The solid-phase auto-synthesis successfully afforded a non-natural DNA-like oligomer bearing 2-aminopyrimidin-4-one as a nucleobase. The synthetic oligomer exhibited reversible formation of a higher-order structure that would be a duplex like natural DNA. The present study means creation of a novel artificial DNA-like system with unordinary odd numbers of genetic alphabets.

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Published online: 29th May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)82
Efficient Synthesis of t-Butyl 3-Alkyl-N-Hydroxy-Oxindole-3-Carboxylates from Di-t-Butyl 2-Nitrophenyl-Malonates

Yu-suke Yamai, Kyoji Ishida, Itaru Natsutani, Shinichi Uesato, Yasuo Nagaoka, and Takaaki Sumiyoshi*

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

Abstract

A selective and efficient synthesis of t-butyl 3-alkyl-N-hydroxy- oxindole-3-carboxylates from di-t-butyl 2-nitrophenylmalonates is described. A tandem reduction-cyclization approach involving reduction of di-t-butyl 2-methyl-(2-nitrophenyl)malonate to di-t-butyl 2-(2-(hydroxyamino)phenyl)-2-methylmalonate followed by accelerated cyclization reaction using a combination of Rh/C and hydrazine monohydrate smoothly and selectively afforded the N-hydroxy-oxindole scaffold. This methodology was successfully applied to gram-scale-synthesis of the t-butyl N-hydroxy-3-methyl-oxindole-3-carboxylate 1 without silica gel column chromatographic separation step.

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Published online: 28th May, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)64
Asymmetric Synthesis of O-Methylneferine

Katsumi Nishimura,* Shinji Horii, and Takao Tanahashi

*Organic Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan

Abstract

Diastereoselective Pictet–Spengler reaction of 2-arylethylamine bearing an N-(R)-1-(1-naphthyl)ethylcarbamoyl group with arylacetaldehyde gave 1-benzyltetrahydroisoquinoline in good yield with moderate diastereoselectivity. The reaction was applied to asymmetric synthesis of O-methyl derivative of neferine, an alkaloid of the lotus embryo, Nelumbo nucifera Gaertner.

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Published online: 23rd May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(F)3
Visible-Light-Promoted Se-Arylation of Diaryl Diselenides with 2-Phenylimidazopyridines in the Presence of Ammonium Iodide: Synthesis of 2-Phenyl-3-(Arylselanyl)Imidazo[1,2-α]Pyridines

Yuki Murata, Keiko Kanasaki, Kaito Kondo, Naoki Kakusawa, Mio Matsumura, and Shuji Yasuike*

*School of Pharmaceutical Sciences, Aichi Gakuin University, 1-100 Kusumoto-cho Chikusa-ku Nagoya city 464-8650, Japan

Abstract

Photoreaction of diaryl diselenides and 2-phenylimidazo[1,2-a]pyridine in the presence of ammonium iodide (20 mol%) using blue LED light led to the formation of 3-(arylselanyl)imidazopyridines in good-to-excellent yields under aerobic conditions. By using various diselenides, this reaction efficiently introduces the selanyl group at the 3-position of the imidazopyridine scaffold

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Published online: 21st May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)79
Total Synthesis of Coriariin B

Hitoshi Abe,* Yoshiyasu Kato, Haruka Imai, and Yoshikazu Horino

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

Abstract

The total synthesis of coriariin B (1), which is a type of ellagitannin, and originally obtained from the leaves of Coriaria japonica, was achieved by esterification between the glucose derivative and partially protected dehydrodigallic acid (5). The HHDP (hexahydroxydiphenoyl) unit was constructed by the oxidative phenol coupling reaction in a stereoselective manner.

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Published online: 18th May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)90
5-((3-Bromoallyl)Sulfonyl)-1H-Tetrazoles for Bromodiene Synthesis

Takuro Suzuki, Seiya Fukagawa, Tatsuhiko Yoshino, Masahiro Anada, and Shigeki Matsunaga*

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

Abstract

Reagents for one-step construction of conjugated bromodienes from aldehydes are described. Various 1-alkyl- and 1-aryl-tetrazoyl bromoallylic sulfones were synthesized and evaluated in bromodiene synthesis. 1-Alkyl-tetrazoyl sulfones selectively afforded (1E,3Z)-bromodienes, while 1-aryl-tetrazoyl sulfones resulted in low selectivity.

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Published online: 18th May, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-17-S(T)4
Palladium-Catalyzed Selective Formation of Substituted Pyrroles from Alkene-tethered Cyclic Oxime Esters

Kazuhiro Okamoto,* Tomohiro Oda, Takuya Shimbayashi, and Kouichi Ohe*

*Deparment of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoudai-katsura, Nishikyo, Kyoto 615-8510, Japan

Abstract

Isoxazol-5(4H)-ones were used as nitrene precursors for the selective formation of trisubstituted pyrroles by applying a palladium-catalyzed decarboxylative ring-reconstruction method. The use of bulky biaryl-type monophosphine ligands was effective for improving the selectivity. Deuterium-labeling experiments suggested a mechanism involving -hydride elimination followed by reductive elimination from an aza--allyl intermediate.

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Published online: 18th May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)45
Preparation of Optically Active 2,2-Disubstituted 5-Hydroxychromenes by the Enzymatic Resolution of Racemic Esters

Mika Kainuma, Ai Yamada, Kazuaki Katakawa, and Takuya Kumamoto*

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

Abstract

Enzymatic kinetic resolution of racemic esters of 2,2-disubstituted 5-hydroxychromenes was examined. Transesterification of acetate using Amano Lipase PS in the presence of t-BuOH was most effective to give the corresponding optically active acetate in 18% yield and 95% ee. The absolute configuration of the acetate was determined as R based on the conversion to teretifolione B with natural absolute configuration.

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Published online: 18th May, 2018

Communication | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)81
Efficient One-Pot Synthesis of Substituted Oxazoles from 3-Trimethylsilylpropargylic Alcohols and Amides by Gold-Catalyzed Substitution Followed by Cycloisomerization

Nobuyoshi Morita,* Aoi Sano, Ayako Sone, Shino Aonuma, Arisa Matsunaga, Yoshimitsu Hashimoto, and Osamu Tamura*

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

Abstract

3-Trimethylsilylpropargylic alcohols 1, on treatment with amides 2 in the presence of catalytic amounts of cationic gold(III), underwent propargylic substitution followed by cycloisomerization. The key of the cycloisomerization, in which the key feature is the β-cation-stabilizing effect of the silicon atom of 3-trimethylsilyl-propargylic alcohols 1.

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Published online: 18th May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)86
Direct Enantioselective Indolylation of Peptidyl Imine for the Synthesis of Indolyl Glycine-Containing Peptides

Tsubasa Inokuma, Kodai Nishida, Akira Shigenaga, Ken-ichi Yamada, and Akira Otaka*

*Graduate School of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan

Abstract

A novel synthetic method involving the direct application of a catalytic asymmetric reaction to peptides was developed. The conditions optimized for the model asymmetric reaction of a simple α-imino amide with an indole derivative were successfully applied to an asymmetric Friedel–Crafts reaction of α-imino peptide possessing a hydrophobic anchor to afford the indolyl glycine-containing peptide. This novel strategy will be of great value for the synthesis of the biologically important peptides bearing varieties of unnatural amino acids.

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Published online: 17th May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)44
Lewis Acid Catalysis in Intermolecular [2+2] Photocycloaddition of Coumarin-3-carboxamide Bearing 2-Oxazolidinone Auxiliary with n-Propyl Vinyl ether and Vinyl Pivalate

Kennosuke Itoh,* Junya Matsuura, Hideaki Kamiya, Ryuki Kudo, Yuki Takahashi, Yuta Hashimoto, Kenji Yoza, Ken Tokunaga, Hideaki Fujii, and Hiroyuki Suga

*Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan

Abstract

Intermolecular [2+2] photocycloaddition reactions between 3-(2-oxo- 2H-chromene-3-carbonyl)oxazolidin-2-one with n-propyl vinyl ether and vinyl pivalate were carried out to give [2+2] cycloadducts in excellent yield with perfect regioselectivity. A Lewis acid catalyst (30 mol%) was moderately effective in accelerating the reaction. Furthermore, enantioselective reactions catalyzed by chiral Lewis acid catalysts (30 mol%) were performed to give cycloadducts in excellent yields with up to 13% ee.

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Published online: 16th May, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)21
Synthesis of Salacinol-d4 as an Internal Standard for Mass-Spectrometric Quantitation of Salacinol, a Potent α-Glucosidase Inhibitor Found in a Traditional Ayurvedic Medicine “Salacia

Genzoh Tanabe,* Sanami Teramae, Yousuke Kunikata, Shinsuke Marumoto, Shuhei Okugawa, Fumihiro Ishikawa, Weija Xie, Toshio Morikawa, and Osamu Muraoka

*Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan

Abstract

Accurate quantitative analysis of trace principles in extracts of biologically active natural medicines relies on the use of reliable internal standards (ISs), which, in the case of liquid chromatography–mass spectrometry (LC-MS) analysis, commonly correspond to isotope-labeled stable analogues of the analytes. Herein, we describe the synthesis of salacinol-1,1,5,5-C-d4 (7), an isotope-labeled stable analogue of salacinol (1), which, in turn, is a potent α-glycosidase inhibitor isolated from Salacia (a traditional Ayurvedic medicine), and show that the isotopic purity of the labeled standard is satisfactory for LC-MS analysis.

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Published online: 14th May, 2018

Short Paper | Special issue | Prepress
DOI: 10.3987/COM-17-S(T)5
Two New Galloyl Glucosides from the Leaves of Castanopsis Fordii

Yong-Lin Huang,* Zhang-Bin Liu, Ya-Feng Wang, Li Ge, Rui-jie He, Jin-Lei Liu, Ke-Di Yang,* and Dian-Peng Li

*Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, NO. 85 Yanshan Street, Guilin, Guangxi 541006, China

Abstract

Two new galloyl glucosides, furan-2-carbonyl 6-C-β-D-(6'-O-galloyl)glucopyranoside (1), grasshopper ketone 5-O-β-D-(6'-O-galloyl)glucopyranoside (2), and one known compound 4-quinolone-2-carboxylic acid, were isolated from ethanol extract of the fresh leaves of Castanopsis fordii (Fagaceae). The chemical structures of these compounds were determined by one and two dimensional (1D and 2D)-NMR, liquid chromatography/time-of-flight/mass spectrometry (LC/TOF/MS), chemical evidence, and comparison with the literature.

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Published online: 14th May, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)65
TFA-Protected Α-Amino Acid N-Hydroxysuccinimide Ester: Application for Inter- and Intramolecular Acylation

Zetryana Puteri Tachrim, Kazuhiro Oida, Fumina Ohashi, Haruna Wakasa, Haruka Ikemoto, Natsumi Kurokawa, Yasuko Sakihama, Yasuyuki Hashidoko, Takeyuki Suzuki, and Makoto Hashimoto*

*Graduate School of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0589, Japan

Abstract

The utilization of N-trifluoroacetyl (TFA)-α-amino acid N-hydroxysuccinimide ester (OSu) derivatives, a promising acylating agent with high storage stability, is reported for Friedel–Crafts acylation into arenes and N-heterocycles. The reaction between TFA-Phe-OSu derivatives and arenes afforded inter- and intramolecular products. TFA-Tyr-OSu derivatives, which possess hydroxyl substituent in the aromatic moiety of phenylalanine, afforded only intermolecular product with benzene. The heterocyclic TFA-Pro-OSu also shows relatively high reactivity toward acylation.

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Published online: 11th May, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)51
Construction of Azaisoflavone Derivatives by Hypervalent Iodine Reagent-Mediated Oxidative Rearrangement of 2’-Nitrochalcone

Akira Nakamura, Reo Takane, Junki Tanaka, Junya Morimoto, and Tomohiro Maegawa*

*School of Pharmaceutical Sciences, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan

Abstract

Fabrication of a synthetic azaisoflavone skeleton from 2’-nitrochalcone was done using oxidative rearrangement with a hypervalent iodine reagent. A key intermediate compound, aminoacetal, was prepared from readily available 2’-nitrochalcone via a PhI(OH)OTs-mediated rearrangement, followed by reduction of the nitro group. A variety of azaisoflavones were obtained in moderate to high yields by treatment of the intermediate compound under acidic conditions.

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Published online: 9th May, 2018

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DOI: 10.3987/COM-18-S(T)83
Synthetic Approach to Oxa-Cage Systems via Ring-Closing Metathesis

Sambasivarao Kotha,* Subba Rao Cheekatla, and Milind Meshram

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

Abstract

Here, we report a new synthetic approach to oxa-cage systems by employing RCM as a key step. These cage systems were assembled starting with easily accessible starting materials by adopting a three-step sequence involving the Grignard addition, allylation followed by RCM.

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Published online: 27th April, 2018

Paper | Special issue | Prepress
DOI: 10.3987/COM-18-S(T)89
Synthesis of 2-Amino-1-Cyanoazulenes: Substituent Effect on 2H-Cyclohepta[b]Furan-2-Ones Toward the Reaction with Malononitrile

Taku Shoji,* Shuhei Sugiyama, Kota Miura, Akira Ohta, Ryuta Sekiguchi, Shunji Ito, Shigeki Mori, and Tetsuo Okujima

*Department of Chemistry, Faculty of Science, Shinshu University, Asahi 3-1-1, Matsumoto, Nagano 390-8621, Japan

Abstract

3-Substituted 2-amino-1-cyanoazulene derivatives were prepared by the reaction of 2H-cyclohepta[b]furan-2-ones with malononitrile in the presence of triethylamine as a base. The great influence of the substituent at their 3-position on the reactivity to form the 2-aminoazulene derivatives was revealed. The intramolecular charge transfer (ICT) characters of 2-amino-1-cyano-3-vinylazulenes were investigated by UV/Vis spectroscopy and theoretical calculations. The structure of compounds 13b and 14b was clarified by single crystal X-ray analysis.

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