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 I. Meyers's Special Issues, Vol. 58, No. 1, 2002
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■ Sulfur-containing Heterocycles Derived by Reaction of N-Thioacylamino Alcohols with Lawesson’s Reagent and Saponification of N-Thioacylamino Esters
Takehiko Nishio* and Hiroshi Sekiguchi
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
The treatment of 2-N-thioacylamino alcohols (1) with Lawesson’s reagent [LR: 2,4-bis(p-methoxyphenyl)-1,3,2,4-dithiaphosphetane 2,4-disulfide] afforded the sulfur-containing heterocycles, 1,3-thiazolines (2) in moderate to good yields, exclusively. The saponification of N-thioacylamino esters (4), which were prepared by the thionation of N-acylamino esters (3) with LR, with K2CO3 gave 3,1-benezothiazines (5) and 3,1-benzoxazines (6).
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■ Some Unexpected Reactions of 2,2-Bis(trifluoromethyl)-1,3-oxazolidin-5-ones
Gábor Radics, Hartmut Schedel, Elisabeth Heistracher, Joachim Sieler, Lothar Hennig, and Klaus Burger*
*Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany
Abstract
2,2-Bis(trifluoromethyl)-1,3-oxazolidin-5-ones and hexafluoroacetone react in dimethyl sulfoxide to give trifluoromethyl substituted 1,3-oxazolidine-4-carboxylate, 3-amino-5,5-bis(trifluoromethyl)-2(5H)-furanone and 4-amino-2,2-bis(trifluoromethyl)-1,3-dioxolanes depending on the substituent pattern of the amino acid. All compounds are formed via a common intermediate, namely N-hexafluoroisopropylidene α-amino acids.
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■ A New Construct of the cis-3a-Aryloctahydroindole Skeleton via the [4+2] Cycloaddition of Furanyl Carbamates
Albert Padwa,* Cheryl K. Eidell, and Stephen M. Lynch
*Department of Chemistry, Emory University, 1515 Pierce Drive, Atlanta, Georgia 30322, U.S.A.
Abstract
Several 2-methylthio-5-amidofurans containing tethered unsaturation were prepared via the reaction of dimethyl(methylthio)-sulfonium tetrafluoroborate (DMTSF) with β-alkoxy-γ-dithiane amides. Thermolysis of these furans resulted in an intramolecular Diels-Alder reaction (IMDAF). The resulting oxa-bridged cycloadducts underwent a subsequent rearrangement to form bicyclic lactams. Model studies were directed toward mesembrine as well as the core skeleton of the 3,4-benzoerythrinane skeleton. Using this cascade sequence, a formal synthesis of the alkaloid erysotrine was accomplished.
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■ Multi-component Reactions of 2-Isopropylideneaziridines: Application to the Synthesis of Enantiopure Neopentylamines
Jerome F. Hayes, Michael Shipman,* Alexandra M. Z. Slawin, and Heather Twin
*School of Chemistry, University of Exeter, Stocker Road, Exeter, Devon, EX4 4QD, U.K.
Abstract
Neopentylamines {(1S,1’S)-7a,b} are made from (S)-2-isopropylidene-1-(1-phenylethyl)aziridine (4) in 73% and 56% yields respectively, and as single diastereomers, using a multi-component reaction (M–CR). The structure of (1S,1’S)-7a is confirmed by X-Ray crystallography. Cleavage of the chiral control element {(S)-PhMeCH} from 7a yields neopentyl type amine (8·HCl) (⊇95%ee). Further experiments reveal the scope and limitations of this M–CR.
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■ Imino Ene Reactions of Enantiopure N-Sulfinylimino Esters: Asymmetric Synthesis of 1-Oxo-1 λ4-isothiazolidine-3-carboxylates
Franklin A. Davis,* Junya Qu, Vaidyanathan Srirajan, Reni Joseph, and Donald D. Titus
*Department of Chemistry, Temple University, Philadelphia, PA 19122, U.S.A.
Abstract
The imino ene reaction of (R)-(-)-N-(tert-butanesulfinyl)iminoacetate (2), allyl benzene and SnCl4 results in a novel rearrangement affording 1-oxide isothiazolidine-3-carboxylate (4) as the major product. The structure of 4 was established by X-Ray crystallography and conversion into α-amino acids that were prepared independently using the sulfinimine-mediated asymmetric Strecker synthesis.
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■ Studies on the Synthesis of Kijanolide: Synthesis of an Advanced Seco-acid Intermediate
William R. Roush,* Hou Chen, and Melissa L. Reilly
*Department of Chemisry, University of Michigan, 930 North University, Ann Arbor, MI 48109-1055, U.S.A.
Abstract
A synthesis of an advanced seco acid intermediate (7) in a projected total synthesis of kijanolide is described. Key steps in the synthesis of 7 include the highly diastereoselective allylation reaction of 15, the Suzuki cross coupling of dienyl iodide (11) and vinylboronic acid (12), and the IMDA reaction of 9. Elaboration of the spirotetronic acid unit of 7 was accomplished by a Dieckmann cyclization of the α-acetoxy ester intermediate derived from the IMDA cycloadduct (39).
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■ Synthesis and Reactions of 3- and 8-Ethynyl-1-azaazulenes
Hiroyuki Fujii, Noritaka Abe,* Noritaka Umeda, and Akikazu Kakehi
*Department of Chemistry, Faculty of Science, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan
Abstract
3-Iodo-1-azaazulenes were easily ethynylated by Sonogashira-Hagihara reaction to give 3-ethynyl-1-azaazulenes. Cyclization of 2-amino-3-ethynyl-1-azaazulene was achieved by heating in the presence of copper(II) acetate or copper(II) trifluoromethanesulfonate, and 1,9-diaza-1H-cyclopent[a]azulene derivatives were obtained. Reaction of 2-chloro-1-azaazulene with lithium phenylacetylide gave 3-chloro-1-(2-chloro-1-azaazulen-8-yl)-2-phenyl-2a-aza-2H-cyclopent[cd]azulene together with 2-chloro-8-phenylethynyl-1-azaazulene.
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■ Asymmetric Synthesis of 4,6-Disubstituted 1,2,3,4,5,6-Hexahydro-5-hydroxypyrimidin-2-ones as Potential HIV-Protease-Inhibitors
Dieter Enders* and Lars Wortmann
*Institut für Organische Chemie, Rheinisch-Westfälische, Technische Hochsch, Professor-Pirlet-Straße 1, D-52074 Aachen, Germany
Abstract
The first asymmetric synthesis of potential HIV protease inhibitors of type III and IV is described. Key step of the synthesis is an auxiliary based stereoselective alkylation by means of the RAMP-/SAMP-hydrazone method starting from a readily available key building block. The synthesis is short and highly versatile in the choice of the substitution pattern as well as the absolute configuration of the products.
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■ Preparation of Novel Heteroisoindoles from Nitropyridines and Nitropyridones
Takashi Murashima,* Keiji Nishi, Ken-ichi Nakamoto, Atsushi Kato, Ryuji Tamai, Hidemitsu Uno, and Noboru Ono*
*Departmnt of Chemistry, Faclty of Science, Ehime University, Matsuyama 790-8577, Japan
Abstract
The reaction of nitropyridine derivatives with ethyl isocyanoacetate in the presence of 1,8-diazabicyclo[5.4.0]undecene proceeded tandem cyclization to give polycyclic pyrrolopyridines or imidazopyridines. On the other hand, N-protected 3-nitro- and 5-nitropyridones and N,N-diprotected 5-nitrouracil gave corresponding bicyclic pyrroles in good yields under the similar conditions.
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■ 4H-[1,2,3]-Thiadiazolo[3,4-a]benzimidazoliumides
Alan R. Katritzky,* George N. Nikonov, Dmytro O. Tymoshenko, and Peter J. Steel
*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, P. O. Box 117200, Gainesville, FL 32611-7200, U.S.A.
Abstract
Thermal rearrangements of 1-(1,2,3-thiadiazol-5-yl)-1H-1,2,3-benzotriazoles afford zwitterionic 3-phenyl-4H-[1,2,3]thiadiazolo[3,4-a]benzimidazol-2-ium-4-ides by intramolecular trapping of thiirene intermediates.
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■ Preparation of 2’,3’-Methano-carbocyclic Nucleosides through the Addition of Diazomethane to 2-Azabicyclo[2.2.1]hept-5-en-3-one
Minoru Ishikura,* Atsushi Murakami, and Nobuya Katagiri
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
The preparation of 2’,3’-methano-carbocyclic analogues of adenosine is reported. The addition of diazomethane to N-substituted 2-azabicylo[2.2.1]hept-5-en-3-one (ABH) (1) provided cyclopropane-fused ABH (3), which was converted to 2’,3’-methano carbocyclic nucleosides (8).
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■ A New Deprotection Procedure for the N-Methoxymethyl Group of N-Methoxymethyl-heterocyclic Compounds
Takeshi Kuwada, Miyako Fukui, Maho Hirayama, Junko Nobuhiro, Tominari Choshi, and Satoshi Hibino*
*Graduate School of Pharmacy and Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan
Abstract
A new deprotection procedure regarding the N-methoxymethyl (MOM) group was revealed during the total synthesis of oxopropalines D and G. We describe the deprotection method of N-MOM-heterocyclic compounds and its utilization.
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■ Silica Gel-catalyzed Regio- and Stereoselective Reactions of Thiocarbonyl Compounds with Optically Active Monosubstituted Oxiranes
Changchun Fu, Anthony Linden, and Heinz Heimgartner*
*Institute of Organic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
Abstract
The reactions of 1,1,3,3-tetramethylindane-2-thione (1) with (S)-2-methyloxirane ((S)-2) and (R)-2-phenyloxirane ((R)-6) in the presence of a Lewis acid such as BF3·Et2O, SnCl4, ZnCl2 or SiO2 in dry CH2Cl2 led to the 1,3-oxathiolanes ((S)-3) and ((R)-4) with Me at C(5′) and C(4′), and to (S)-7 with Ph at C(4′), respectively (Schemes 2 and 3). The SiO2-catalyzed reaction of 4,4-dimethyl-2-phenyl-1,3-thiazole-5(4H)-thione (8) with (R)-6 gave two diastereoisomers ((5S,8S)-9) and ((5R,8S)-9) (Scheme 4). In the case of adamantane-2-thione (10) and (S)-2 or (R)-6 with ZnCl2 or SiO2 as catalysts, (S)-11 and (R)-12 with Me at C(5′) and C(4′), respectively, and (S)-13 with Ph at C(4′), were formed. In addition, an unexpected isomer ((R)-14) with Ph at C(5′) and 1,3-dioxolane ((S)-15) were isolated as minor products (Schemes 5 and 6). The structure of (S)-13 was confirmed by X-Ray crystallography (Figure 1). These results show that the SiO2-catalyzed addition of oxiranes to C=S bonds proceeds with high regio- and stereoselectivity via an SN2-type mechanism.
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■ Hydroamination of Alkynes Catalyzed by Palladium/Benzoic Acid
Leopold Mpaka Lutete, Isao Kadota, Akinori Shibuya, and Yoshinori Yamamoto*
*Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
The reaction of internal alkynes (1) with amines (2) in the presence of catalytic amount of Pd(PPh3)4 and benzoic acid in dioxane at 100°C gave the allylic amines (3) in good to excellent yields. The intramolecular reaction of alkynes with tethered amino groups (4) gave 2-vinylpyrrolidines and 2-vinylpiperidines (5) in good to excellent yields.
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■ Quinolone Analogues 5. Synthesis of 1-Methylpyridazino[3,4-b]quinoxalin-4(1H)-ones
Yoshihisa Kurasawa,* Jun Takizawa, Yuka Maesaki, Ayaka Kawase, Yoshihisa Okamoto, and Ho Sik Kim
*School of Pharmaceutical Sciences, Kitasato University, Shirokane, Minato-ku, Tokyo 108-8641, Japan
Abstract
The reaction of the quinoxaline N-oxide (8a) with diethyl ethoxymethylenemalonate gave the 1,4-dihydropyridazino[3,4-b]quinoxaline-4,4-dicarboxylate (10c), whose reaction with a base afforded the 1,5-dihydropyridazino[3,4-b]quinoxaline-4-carboxylate (6a). The oxidation of compound (6a) with nitrous acid provided the 1,4-dihydro-4-hydroxypyridazino[3,4-b]quinoxaline-4-carboxylate (7), whose reaction with potassium hydroxide gave 7-chloro-1-methylpyridazino[3,4-b]quinoxalin-4(1H)-one (5a). On the other hand, the reaction of the quinoxaline N-oxide (8b) with acetylacetaldehyde dimethyl acetal afforded 4-acetyl-1,5-dihydro-1-methylpyridazino[3,4-b]quinoxaline (6b), whose oxidation with selenium dioxide provided 1-methylpyridazino[3,4-b]quinoxalin-4(1H)-one (5b).
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■ Synthesis of Linear and Cyclic Hexapeptides with Nε-(1,2-Dihydro-1-hydroxy-2-oxopyrimidin-4-yl)-L-lysyl-β-alanyl as the Repeating Unit and Properties of Their Iron(III) Complexes
Akira Katoh,* Yuichi Inoue, Hitoshi Nagashima, Yasushi Hikita, Junko Ohkanda, and Ryota Saito
*Department of Applid Chemistry, Faculty of Engineering, Seikei University, Musashino, Tokyo 180-8633, Japan
Abstract
Linear and cyclic hexapeptides including Nε-(1,2-dihydro-1-hydroxy-2-oxopyrimidin-4-yl)-L-lysyl-β-alanyl as the repeating unit have been synthesized. These hexapeptides formed 1:1 iron(III) complexes; λmax 466 nm and ε 4700 for a linear hexapeptide (8), and λmax 458 nm and ε 4300 for a cyclic hexapeptide (9). The relative stability constants of 8- and 9-iron(III) complexes were estimated to be 26.1 and 28.0, respectively. A linear hexapeptide (8)-iron(III) complex predominantly existed in δ-configuration. From kinetic data on iron(III) removal from human transferrin, a linear hexapeptides (8) was found to efficiently remove three times as much iron(III) from transferrin as desferrioxamine B, only a chemotherapeutic agent for the iron overload disease.
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■ Synthesis of Sterically Demanding 3-Silylpyridines and Their Use in Asymmetric Synthesis with Chiral N-Acyliminium Ions
Cornelia E. Hoesl, Jörg Pabel, Kurt Polborn, and Klaus Th. Wanner*
*Institut für Pharmazie, Zentrum für Pharmaforschung, Universität München, Butenandtstr. 5-13 Haus C, D-81377 München, Germany
Abstract
A convenient one-pot procedure for the synthesis of sterically hindered 3-silylpyridines is reported. It is based on 3-lithiopyridine that is generated from commercially available 3-bromopyridine and subsequently trapped with silyl chlorides. 3-Triisopropylsilylpyridine was employed in an asymmetric electrophilic α-amidoalkylation reaction providing a chiral N-acyl-1,2-dihydropyridine in very high regio- and diastereoselectivity. Conjugate reduction of the diene moiety and removal of the chiral auxiliary led to the corresponding 1,2,3,6-tetrahydropyridine in enantiomerically pure form.
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■ Formation of Heterocyclic Derivatives of α-Amino Acids Using Vicinal Tricarbonyl Methodology
Harry H. Wasserman,* Yun Oliver Long, Rui Zhang, and Jonathan Parr
*Department of Chemistry, Yale University, P. O. Box 208107, New Haven, CT 06520-8107, U.S.A.
Abstract
Monoaldehydes derived from diesters of N-protected aspartic and glutamic acids have been reacted with precursors of vicinal tricarbonyl esters to form electrophilic products. These substances were converted to heterocyclic derivatives of the amino acids.
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■ A New Synthetic Approach to Azuleno[1,2-c]thiophenes
Kimiaki Imafuku* and Dao-Lin Wang
*Department of Chemistry, Faculty of Science, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan
Abstract
A variety of methyl 3-acetyl-2-bromomethylazulene-1-carboxylates (4aa-ae) and 3-acetyl-2-bromomethylazulene-1-carbonitriles (4ba-be) were obtained by the bromination of the corresponding 1-methoxycarbonyl- and 1-cyano-substituted 3-acetyl-2-methylazulenes (2aa-ae, 2ba-be), respectively, with N-bromosuccinimide. These azulenes (4aa-ae, 4ba-be) reacted with thioacet-amide to give azuleno[1,2-c]thiophenes (7aa-ae, 7ba-be) in moderate yields. This reaction provides a new procedure for synthesis of thiophene-fused azulenes.
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■ A Synthesis of (1S,2R,8R,8aR)-8-Hydroxy-1,2-(isopropylidinedioxy)indolizidin-5-one from D-Ribose: Improved Access to (-)-Swainsonine and Its Analogs
William H. Pearson,* Yi Ren, and Jeremiah D. Powers
*Department of Chemisry, University of Michigan, 930 North University, Ann Arbor, MI 48109-1055, U.S.A.
Abstract
A short synthesis of the lactam (4), (1S,2R,8R,8aR)-8-hydroxy-1,2-(isopropylidenedioxy)indolizidin-5-one, from D-ribose is reported. This compound is a useful intermediate for the synthesis of analogs of the anticancer agent swainsonine (1) as well for swainsonine itself.
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■ Aryl Radical Cyclization of Chiral 3-Allyl-2-(2-bromophenyl)-1,3-oxazolidines with Tributyltin Hydride
Takayasu Yamauchi, Jumpei Sugiyama, and Kimio Higashiyama*
*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
Stereoselective radical cyclization of (4R)-3-allyl-2-(2-bromophenyl)-4-phenyl-1,3-oxazolidine promoted by the initiator/tributyltin hydride system constructed the chiral oxazolo[2,3-a]tetrahydroisoquinoline skeleton. These tricyclic compounds were transformed into 4-alkyl-1,2,3,4-tetrahydroisoquinolines and 1,4-dialkyl-1,2,3,4-tetrahydroisoquinolines.
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■ Studies on (1S)-N-(1-Phenylethyl)phthalimide: Synthesis of Both Chiral Spiro Indane and Benzazepine Derivatives
Abderrahim Chihab-Eddine, Adam Daïch,* Abderrahim Jilale, and Bernard Decroix
*Laboratoire de Chimie, URCOM, Faculté des Sciences et Techniques, Université du Havre, 25 Rue Philippe Lebon, B.P. 540 76058 Le Havre Cedex, France
Abstract
Chiral spiro indane and benzazepine compounds in isoindolinone series were prepared easily by π-cationic cyclization of the N-acyliminium ions (5-9) or the acylium ion (17) precursors with trifluoroacetic acid or aluminum trichloride, respectively. The stereochemistry and the ratio of diastereomeric mixtures observed during these process were also discussed.
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■ New Chiral Ligands, Pyridinooxathianes, for Palladium-catalyzed Asymmetric Allylic Alkylation
Yuko Okuyama, Hiroto Nakano,* Chizuko Kabuto, Erica Nozawa, Kouichi Takahashi, and Hiroshi Hongo
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
New types of pyridinooxathiane ligands have been synthesized and their abilities as chiral catalysts examined in the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate.
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■ Total Synthesis and Absolute Configuration of Radiosumin, a Strong Trypsin Inhibitor from the Blue-Green Alga Plectonema radiosum
Hirohide Noguchi, Toyohiko Aoyama,* and Takayuki Shioiri*
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
Radiosumin (1), a strong trypsin inhibitory dipeptide isolated from the freshwater blue-green alga Plectonema radiosum (NIES-515), was synthesized for the first time by use of the hetero Diels-Alder reaction, the Horner-Wadsworth-Emmons reaction, the Corey-Winter reaction, regioselective hydrogenation, and reduction with zinc and formic acid as key steps, which unambiguously determined the absolute configuration of the structurally unique and biologically intriguing aquatic natural product (1).
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■ Synthesis and Reactions of Enantiopure 1-Acyl-2-[triaryl(alkyl)silyl]-2,3-dihydro-4-pyridones
Daniel L. Comins,* Michael O. Killpack, Emilie Despagnet, and Emmanuel Zeller
*Department of Chemistry, North Carolina State Univesity, Raleigh, NC 27695-8204, U.S.A.
Abstract
The addition of triphenylsilyl- or dimethylphenylsilymagnesium bromide to certain chiral 1-acylpyridinium salts affords C-2 silylated dihydro-4-pyridones in good yield and high diastereoselectivity (84 – 96% de). Reduction and substitution reactions of these heterocycles were examined to explore their utility as chiral building blocks. Several highly stereoselective transformations were observed.
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■ Dendroamide A, Nostocyclamide and Related Cyclopeptides from Cyanobacteria. Total Synthesis, together with Organised and Metal-templated Assembly from Oxazole and Thiazole-based Amino Acids
Anna Bertram and Gerald Pattenden*
*School of Chemistry, University of Nottingham, Nottingham NG7 2RD, U.K.
Abstract
Oxazole and thiazole-based amino acids (15-18) are shown to undergo organised and metal-templated assemblies leading to novel cyclic peptides. Thus, a 1:1:1 mixture of the amino acids (15, 16 and 17) undergo cyclisation in the presence of FDPP producing the natural hexapeptide dendroamide A (4), together with its positional isomer (33) and other cyclic trimers in a combined yield of 75%. Likewise, a mixture of 15, 16 and 18 cyclised to nostocyclamide (6), isolated from a cyanobacterium, and equal amounts of the analogues (36, 37 and 38) in a combined yield of 65%. The proportions of the cyclopeptide products produced in these novel cyclooligomerisations varied when the cyclisations were carried out in the presence of various metal ions, e.g. Cu2+, Ca2+, Na+, K+, Ag+. A brief discussion of the influence of metals in controlling the outcome of some of these reactions is given.
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■ The Synthesis of Spirooxindole Pyrrolidines via an Asymmetric Azomethine Ylide [1,3]-Dipolar Cycloaddition Reaction
Paul R. Sebahar and Robert M. Williams*
*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.
Abstract
The asymmetric [1,3] dipolar cycloaddition reactions of azomethine ylides derived from 5,6-diphenylmorpholin-2-one with various aldehydes and ethyl oxindolylideneacetate are described. Addition of an aldehyde to the morpholin-2-one, under essentially neutral conditions, results in the preferential formation of the E-ylide which then reacts with the dipolarophile to yield spirooxindole pyrrolidine derivatives in moderate to excellent regio- and diastereoselectivities. The resulting cycloadducts were easily separated by column chromatography and converted to the corresponding amino acid methyl esters through catalytic hydrogenolysis.
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■ A Synthesis of Some Novel 2-Phenyl- and 5-Bromo-substituted Aplysinopsin Analogues
Lovro Selic, Simon Recnik, and Branko Stanovnik*
*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, SLO-1000 Ljubljana, Slovenia
Abstract
5-(2-Phenyl-1H-indol-3-ylmethylene)-2-thioxoimidazolidin-4-one (2) and its oxo derivatives as well as some novel 5-bromoaplysinopsin analogues were synthesized employing dimethylamine substitution in N,N-dimethyl-methylideneimidazolidinones (6).
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■ Simple Synthesis of Racemic Pyrrolo[2,3-b]indoles: Formal Total Synthesis of (±)-Physostigmine
Riichiro Tsuji, Masako Nakagawa, and Atsushi Nishida*
*Graduate School of Pharmaceutical Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Racemic pyrrolo[2,3-b]indoles were efficiently synthesized by the reaction of aromatic hydrazines with 4-chloro-2-methylbutanal. A formal total synthesis of physostigmine was achieved.
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■ Thermodynamically Controlled Photocycloaddition of 5-Fluoro-1,3-dimethyluracil to Naphthalenes
Kazue Ohkura, Tatsuyuki Sugaoi, Akiyo Sakushima, Ken-ichi Nishijima, Yuji Kuge, and Koh-ichi Seki*
*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
Abstract
UV-Irradiation of 5-fluoro-1,3-dimethyluracil (5-FDMU) and 1-acetonaphthone (1a) afforded trans-1,4-adduct, ethenobenzoquinazoline, (2) having an acetyl group at the C-10 bridgehead carbon, together with the cis-isomer (3). The cis-adduct (3) is more fragile than 2 in the dark at ambient temperature, and is more quickly converted back to the starting 1a and 5-FDMU through cycloreversion. Thus, the trans-adduct (2) comes to the predominant product when irradiation is prolonged. Similar irradiation of 1-naphthonitrile afforded cis-ethenobenzoquinazoline-10-carbonitrile (6) and the trans-isomer (7) as the kinetically controlled cycloadducts together with cis-ethenobenzoquinazoline with a CN group on the benzene moiety (5) as thermodynamically controlled product.