HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Albert Padwa's Special Issues,Vol. 84, No. 1, 2012
Published online: 13th September, 2011
■ Design and Synthesis of G-Quadruplex Ligands Bearing Macrocyclic Hexaoxazoles with Four-Way Side Chains
Keisuke Iida, Satoki Majima, Terumi Ohtake, Masayuki Tera, Kazuo Shin-ya, and Kazuo Nagasawa*
*Division of Biotechnology and Life Science, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan
Abstract
Macrocyclic hexaoxazole compounds bearing four-way side chains L2H2-(4M)6OTD derivatives 3 and 4 were synthesized as new G-quadruplex ligands. Stabilization of G-quadruplex forming oligonucleotides in human telomeres, c-kit, bcl-2, and c-myc with those compounds was evaluated by the FRET (fluorescence resonance energy transfer) assay. These compounds showed less stabilizing ability compared to the ligand possessing two-way side chain of L2H2-(4M)6OTD (2d).
Published online: 24th October, 2011
■ Reactions of an Overcrowded Silylene with Pyridines: Formation of a Novel 2H-1,2-Azasilepine and Its Further Cycloaddition
Yoshiyuki Mizuhata, Takahiro Sato, and Norihiro Tokitoh*
*Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
Abstract
The reactions of an overcrowded silylene [Tbt(Mes)Si:] with two types of pyridines were performed. In the case using pyridine, a unique 2:2 adduct bearing five, six, and seven-membered rings was obtained. On the other hand, the reaction with N,N-dimethyl-4-aminopyridine (DMAP) afforded the corresponding 1:1 adduct having a 2H-1,2-azasilepine skeleton.
Published online: 13th January, 2011
■ Deuterium-Labeled Benzyladenine: Synthesis and Application as a Surrogate
Nkaelang Modutlwa, Hiroyuki Tada, Yoshiki Sugahara, Koichi Shiraki, Nobuyuki Hara, Yoshihiro Deyashiki, Tomohiro Maegawa, Yasunari Monguchi,* and Hironao Sajiki*
*Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu 501-1196, Japan
Abstract
N6-Benzyladenine (benzyladenine), a plant growth regulator, was efficiently deuterated by the hydrogen–deuterium (H–D) exchange reaction catalyzed by palladium on carbon-ethylenediamine complex [Pd/C(en)], while use of palladium on carbon (Pd/C) as a catalyst led to a low deuterium incorporation at room temperature or complete removal of the N6-benzyl group at 110 °C or higher temperature. The obtained benzyladenine-d5 was used as an internal standard (surrogate) for the quantification of residual benzyladenine in fruits, vegetables, cereals, and beans using LC/MS/MS. Satisfactory recovery of benzyladenine between 94.2 and 105.7% (100.4% on the average) was obtained. The agrochemical could be detected within the concentration range of 0.25–0.50 ng/g in agricultural products using the present quantification method.
Published online: 14th February, 2011
■ Synthesis of Stereodefined 3,4-Disubstituted Piperidines through Rearrangement of 2-(2-Bromo-1,1-dimethylethyl)azetidines
Karen Mollet, Leen Broeckx, Matthias D’hooghe,* and Norbert De Kimpe*
*Faculty of Bioscience Engineering, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium
Abstract
cis-2-(2-Bromo-1,1-dimethylethyl)azetidines, synthesized by monochloroalane reduction of the corresponding β-lactams, were shown to be excellent building blocks for the synthesis of stereodefined 4-bromo-, 4-fluoro-, 4-acetoxy- and 4-hydroxypiperidines in DMSO. During these transformations, the initially formed bicyclic azetidinium intermediates underwent ring opening by a variety of nucleophiles.
Published online: 16th March, 2011
■ Enamino Esters in the Synthesis of Heterocyclic Systems. Transformation of Dimethyl Acetone-1,3-dicarboxylate into Polysubstituted 1,6-Naphthyridine-8-carboxylates
Jože Šporar, Jure Bezenšek, Uroš Uršič, Amalija Golobič, Jurij Svete, and Branko Stanovnik*
*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia
Abstract
A simple two-step synthesis of 1,6-naphthyridine derivatives is described. Methyl 2-(2-methoxy-2-oxoethyl)-6-oxo-1,6-dihydropyridine-3-carboxylate (3), prepared from dimethyl acetone-1,3-dicarboxylate (1) and propyolic acid amide (2) according to the known procedure, was transformed with N,N-dimethylformamide dimethyl acetal (DMFDMA) first into 2-[1-(dimethylamino)-3-methoxy-3-oxoprop-1-en-2-yl]-6-oxo-1,6-dihydropyridine-3-dicarboxylate (4). This was followed by reaction with monosubstituted hydrazines 5a-h to afford substituted 1,6-naphthyridine-8-carboxylates 7a-h.
Published online: 9th May, 2011
■ Synthesis of Benzotropone-Annulated 1-Azaazulenes and Related Compounds by Suzuki-Miyaura Coupling / Aldol Condensation Cascade Reaction and Evaluations of Their Cytotoxic Activity against HeLa S3 Cells
Makoto Nakatani, Hiroyuki Fujii,* Toshihiro Murafuji, Takahiro Gunji, Reiko Ikeda, Takeo Konakahara, and Noritaka Abe*
*Department of Industrial Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
One-pot Suzuki-Miyaura coupling/aldol condensation cascade reactions of 3-acetyl-2-bromo-1-azaazulene (1b) with 2-formylphenylboronic acid and the reaction of 2-bromo-3-formyl-1-azaazulene (6b) with 2-acetylphenylboronic acid gave 5-azacyclohepta[b]benz[h]azulen-11(11H)-one (5) and 5-azacyclohepta[b]benz[h]azulen-13(13H)-one (8), respectively, in good yields. The 13-hydroxy-12,13-dihydro-derivative (4) of 5 was isolated as an intermediate in the former reaction. Similar reaction of 1b with 2-formylthiophene-3-boronic acid under similar conditions gave 4-aza-1-thia-1,10-dihydroazuleno[2,1-e]azulen-10-one (10) in high yield. Similar reaction of 1b with 3-formythiophene-2-boronic acid did not give a corresponding cyclization product, instead 3-acetyl-1-azaazulen-2(1H)-one was obtained. Compounds (4, 5, and 10) showed strong cytotoxic activity against HeLa S3 cells, whereas compound (8) did not show the cytotoxic activity.
Published online: 23rd May, 2011
■ Model Studies Towards the Total Synthesis of the Stemona Alkaloid 1-Hydroxyprotostemonine: Synthesis of ent-1-Hydroxystemoamide
Nalivela Kumara Swamy and Stephen G. Pyne*
*School of Chemistry, Faculty of Science, University of Wollongong, Wollongong NSW 2522 , Australia
Abstract
As part of a model study towards the total synthesis of Stemona alkaloid 1-hydroxyprotostemonine 1, we have achieved the synthesis an A-B-C ring precursor, ent-1-hydroxystemoamide. Key steps involve an ene-yne RCM reaction and a diastereoselective dihydroxylation-lactonization reaction.
Published online: 27th May, 2011
■ Synthesis of 1,3,5-Triazineselones from Imidoyl Isoselenocyanates and Amidines
Yuehui Zhou, Anthony Linden, and Heinz Heimgartner*
*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Abstract
Whereas the reaction of N-phenylbenzimidoyl isoselenocyanate (1a) with N-phenylbenzamidine (5a) at room temperature gave the corresponding 1,3,5-triazine-2(1H)-selone (6a), the analogous reaction with the unsubstituted benzamidine (5b) led to di-1,3,5-triazin-2-yl diselenide (7b) via oxidative dimerization of the intermediate 1,3,5-triazine-2-selenol. In a similar manner, 1 and 2-amino-3,4,5,6-tetrahydropyridine (8) yielded the cyclohexa-1,3,5-triazine- 4-selone (9), which, in the presence of a strong base, reacted with a second molecule of isoselenocyanate to give the tricyclic 1,3,5-triazineselone (10). Finally, 2-amino-4,5-dihydro-1,3-thiazole (11) underwent the reaction with various isoselenocyanates (1) to yield 1,3-thiazolo[3,2-a][1,3,5]triazine-4-selones (12).
Published online: 29th June, 2011
■ Natural Products-Based Insecticidal Agents 8. Design, Semisynthesis and Insecticidal Activity of Novel O-(Deoxypodophyllotoxin-4’-yl)-(N-((un)substituted benzyl)indol-3-yl)glyoxylesters against Mythimna separata Walker
Yi Wang and Hui Xu*
*Laboratory of Pharmaceutical Design & Synthesis, College of Life Sciences, Northwest A & F University, Yangling, Shaanxi, 712100, China
Abstract
A series of novel O-(deoxypodophyllotoxin-4′-yl)-(N-((un)substituted benzyl)indol-3-yl)glyoxylesters (8a-j) were prepared and their insecticidal activities were evaluated against the pre-third-instar larvae of Mythimna separata Walker in vivo at the concentration of 1 mg/mL. Compounds 8a, 8e-g, and 8i exhibited more potent insecticidal activity than or comparable to toosendanin, a commercial insecticide derived from Melia azedarach. Generally, it obviously suggested that the methyl group at the 6-position on the indolyl ring, the chlorine atom at the 3-position on the benzyl moiety, and introduction of the substituent on the hydroxyl group at the C-4′ position of 4′-demethyl-4-deoxypodophyllotoxin were important for the insecticidal activity.
Published online: 2nd June, 2011
■ Efficient Microwave-Assisted Synthesis of 1,2,4-Triazole-Based Peptidomimetics Using Benzotriazole Methodology
Finn K. Hansen, Lucas K. Beagle, Ekaterina Todadze, and Alan R. Katritzky*
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, U.S.A.
Abstract
A microwave-assisted three-step protocol allowed the rapid and convenient construction of a series of 1,2,4-triazole substituted amino acids and dipeptides as potential building blocks for peptidomimetics.
Published online: 13th June, 2011
■ Synthetic Approach to N,N,N',N'-Tetrakis[(2-pyridylmethyl)ethylenediamine] (TPEN) Derivatives through Ruthenium-Catalyzed-[2+2+2]cycloaddition
Yuji Miyazaki, Fujimaru Tanaka, Kenji Takeshita, and Atsunori Mori*
*Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Abstract
Hydrophobic TPEN (N,N,N',N'-tetrakispyridylmethyl-1,2-ethylenediamine) derivatives are prepared by [2+2+2]cycloaddition of 1,ω-diyne and bromoacetonitrile leading to bromomethylpyridine and following reaction of 1,2-ethylenediamine. The obtained TPEN derivatives are employed for extraction of a soft metal ion such as cadmium(II).
Published online: 19th August, 2011
■ Synthesis and Reactivity of Novel 1H-Isochromeno[3,4-d]imidazol-1-onium Salts
Bart I. Roman, Marie Guégan, Nils De Vos, Cedric Maton, and Christian V. Stevens*
*Faculty of Bioscience Engineering, Department of Sustainable Organic Chemistry and Technology, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium
Abstract
A straightforward and convenient preparation of 25 novel imidazolium salts from the corresponding 1H-isochromeno[3,4-d]imidazolones is described, employing either a quaternization or a quaternization/anion metathesis strategy. The nature of the anion has a major influence on the melting point of these imidazolium salts (BF4 > I, PF6 > N(Tf)2, N(CN)2 > OTf).
Published online: 21st June, 2011
■ Oxaheterocycles: Di- and Trioxabenzo[3,4]cyclohepta[1,2-a]naphthalene-6,7-diones and Dibenzo[a,c]cycloheptene-3-carbonitriles
Hardesh K. Maurya, Ramendra Pratap, Vishnu K. Tandon,* Pushyamitra Mishra, Brijesh Kumar, and Vishnu Ji Ram*
*Department of Chemistry, University of Lucknow, Lucknow, U.P. 226007, India
Abstract
An efficient and convenient synthesis of 9-aryl-11,12-dihydro-13H-5,8-dioxabenzo[3,4]cyclohepta[1,2-a]naphthalene-6,7-diones and 9-aryl-11,12-dihydro-5,8,13-trioxabenzo[3,4]cyclohepta[1,2-a]naphthalene-6,7-diones has been delineated through base catalyzed condensation-cyclization of 4-methylsulfanyl-2-oxo-2,5,6,7-tetrahydro-1-oxadibenzo[a,c]cycloheptene-3-carbonitriles and 4-methylsulfanyl-2-oxo-5,6-dihydro-2H-1,7-dioxadibenzo[a,c]cycloheptene-3-carbonitriles with aryl methyl ketone separately. We have also reported the synthesis of 2-aryl-4-sec-amino-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-3-carbonitriles through ring transformationof 4-sec-amino-2-oxo-2,5,6,7-tetrahydro-1-oxadibenzo[a,c]cycloheptene-3-carbonitriles with aryl methyl ketones in the presence of powdered KOH/NaOH in DMF. We have successfully synthesized 4-aryl-2-(piperidin-1-yl)-5,6-dihydro-7-oxadibenzo[a,c]cycloheptene-1-carbonitriles as isomeric products through ring transformation of 6-aryl-4-sec-amino-2H-pyran-2-one-3-carbonitriles by 3,4-dihydro-2H-benzo[b]oxepin-5(2H)-ones.
Published online: 8th July, 2011
■ Ni- and Cu-Catalyzed Coupling Reactions Using 2-(4,5-Dihydro-1H-imidazo-2-yl)phenol as a Versatile Phosphine-Free Ligand
Satoshi Haneda, Kazuhiko Sudo, and Masahiko Hayashi*
*Department of Chemistry , Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Abstract
We have disclosed 2-(4,5-dihydro-1H-imidazo-2-yl)phenol (1) worked efficiently as a ligand in Ni-catalyzed Suzuki-Miyaura coupling reactions and Cu-catalyzed N-cyclopropylation of indoles using cyclopropylboronic acid.
Published online: 10th June, 2011
■ Regioselective α-Monochlorination of N-Protected-3-piperidones
Pradeep S. Chauhan, Max M. Majireck, and Steven M. Weinreb*
*Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.
Abstract
A direct procedure for regioselective α-monochlorination of various N-sulfonyl and N-acyl-protected-3-piperidones with N-chlorosuccinimide (NCS) and Amberlyst-15 ion exchange resin is reported which leads predominantly (or exclusively) to 4-chloro-3-piperidones in all cases.
Published online: 29th July, 2011
■ Improved Synthesis of the New Furo[3,2-h]isoquinoline Alkaloids TMC-120B and TMC-120A, and Their Inhibitory Activities against IFN-γ and IL-4 Production
Tominari Choshi,* Teppei Kumemura, Haruto Fujioka, Yuhzo Hieda, and Satoshi Hibino*
*Graduate School of Pharmacy and Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan
Abstract
In our synthetic route of TMC-120B (2), the synthetic intermediate, methyl [7-(methoxycarbonyl)-3-methyl-8-isoquinolyloxy]acetate (8) was newly synthesized in seven steps along with an improvement of the overall yield. The catalytic hydrogenation of TMC-120B (2) was also improved. Inhibition of interferon-γ and interleukin-4 production by TMC-120A (1), TMC-120B (2), and their derivative 4 was evaluated. The results indicated that these compounds are selective inhibitors of Th1 cell function.
Published online: 7th July, 2011
■ Synthesis of Fused Tricyclic Heterocycles by Condensation, Cyclization, Dipolar Cycloaddition Cascade of α-Benzenesulfonyl and α-Phenylthio Substituted Aldehydes
Iain Coldham,* Adam J. M. Burrell, Luke Watson, Niall Oram, and Nathaniel G. Martin
*Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, U.K.
Abstract
Heating α-benzenesulfonyl- or α-phenylthio-aldehydes that contain a tethered alkyl chloride and alkene originating from the α- position of the aldehyde with hydroxylamine sets up a cascade (tandem) reaction sequence involving condensation to an intermediate oxime, then cyclization to an intermediate nitrone, then intramolecular dipolar cycloaddition. The fused tricyclic products are formed with complete stereochemical control and were converted in two steps either to the natural product (±)-myrioxazine A or to a 1,3-oxazine that is present in some yuzurimine type Daphniphyllum alkaloids.
Published online: 5th August, 2011
■ Synthesis of Nalbuphine from Oripavine via N-Demethylation of N-Cyclobutylmethyl Oripavine
Ales Machara, D. Phillip Cox, and Tomas Hudlicky*
*Department of Chemistry, Brock University, St. Catharines, Ontario, L2S 3A1, Canada
Abstract
A short synthesis of nalbuphine from oripavine is reported via N-demethylation of N-cyclobutylmethyloripavine ammonium bromide.
Published online: 12th July, 2011
■ Unusual Base-Induced Rearrangement of exo-9-Oxabicyclo[4.2.1]non-7-ene Oxide to exo-8-Hydroxybicyclo[3.3.0]octan-2-one
David M. Hodgson,* Matthew A. H. Stent, Robert S. Paton, and Francis X. Wilson
*Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Abstract
Reaction of exo-9-oxabicyclo[4.2.1]non-7-ene oxide with n-BuLi gives exo-8-hydroxybicyclo[3.3.0]octan-2-one. Potential reaction pathways for this unusual rearrangement were evaluated with the aid of computational studies. The process is proposed to proceed by elimination to a transient allene oxide, which rearranges to a trans-epoxide enolate before undergoing epoxide α-lithiation and transannular C−H insertion.
Published online: 26th July, 2011
■ Synthesis of Human Milk Oligosaccharides: 2'- and 3'-Fucosyllactose
Claney L. Pereira and Frank E. McDonald*
*Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, U.S.A.
Abstract
The human milk oligosaccharides 2'-fucosyllactose and 3-fucosyllactose were synthesized using a selectively protected 1-O-allyllactosyl acceptor and a 1-O-trichloroacetimidate fucosyl donor. This synthesis utilized fewer toxic reagents and milder reaction conditions as compared to previous syntheses.
Published online: 20th September, 2011
■ Flash Vacuum Pyrolysis of Naphthalen-1-yl and -2-yl Prop-2-ynoate
Vit Lellek and Hans-Jürgen Hansen*
*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Abstract
In contrast to phenyl prop-2-ynoates, which give on flash vacuum pyrolysis (FVP, 650 °C, 0.13 Pa, o-xylene) the corresponding 2H-cyclohepta[b]furan-2-ones in acceptable yields, leads the FVP of naphthalen-1-yl prop-2-ynoate (5a) to the formation of benzo[1,2-b]furan (6, 17%) and naphthalen-1-ol (25%). A blue component (1.8%), which is found in the product mixture, turned out to be (E)-2-(4-metyl-2H-benzo[h]chromen-2-ylidene)naphthalen-1(2H)-one ((E)-7). On the other hand, naphthalene-2-yl prop-2-ynoate (5b) behave on FVP “normal” in that a cycloaddition dimer 11 (15%) of the primarily formed benzo[4,5]cyclohepta[1,2-b]furan-2(2H)-one (10) was isolated from the pyrolysate.
Published online: 15th August, 2011
■ Rapid One-Pot Versatile Preparation of 2-Aminobenzothiazoles by Highly Efficient Copper(I)-Catalyzed Inorganic Base-Free Intramolecular Cyclization
Haruki Sashida* and Mamoru Kaname
*Faculty of Pharmaceutical Sciences, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan
Abstract
The convenient and versatile one-pot preparation of the 2-aminobenzothiazoles by the highly efficient copper(I)-catalyzed intramolecular cyclization of commercially available o-halophenyl isothiocyanates with N-nucleophiles has been accomplished. The reaction of not only the o-iodophenyl or o-bromophenyl isothiocyanates, but also the o-chlorophenyl one proceeded under inorganic base-free conditions.
Published online: 29th July, 2011
■ 1,3-Dipolar Cycloaddition of D-Xylose Derived Nitrone with Methyl Acrylate. Synthesis of Chiral Pyrrolidinones and Pyrrolidines
Gabriel Podolan, Lubor Fišera,* Jozef Kožíšek, and Marek Fronc
*Catalysis and Petrochemistry, Institute of Organic Chemistry, Slovak University of Technology, Bratislava 812 37, Slovak Republic
Abstract
Several new 3-hydroxysubstituted pyrrolidinones and pyrrolidines with a long-polyolic chain were prepared from chiral isoxazolidines. The cycloaddition of the chiral nitrone 4 derived from D-xylose with methyl acrylate proceeded with very good diastereoselectivity for the anti-trans isoxazolidine 5a. The results show that the method has potential use in the preparation of pyrrolidinones and pyrrolidines containing carbohydrate residues.