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
Arnold Brossi's Special Issues, Vol. 39, No. 2, 1994
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■ Synthesis of a New Macrocycle Containing Tin and Selenim, 1,9-Diselena-5,5,13,13-tetramethyl-5.13-distannacyclohexadecane, and Related Compounds
Hisashi Fujihara, Yutaka Takaguchi, and Naomichi Furukawa*
*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan
Abstract
New cyclic compounds containing heavier group 14 and 16 elements, 1-selena- or 1-thia-5,5-dimethyl-5-stannacyclooctane (1 or 3) and 1,9-diselena- or 1,9-dithia-5,5,13,13-tetramethyl-5,13-distannacyclohexadecane (2 or 4), and its selenonium derivatives have been synthesized.
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■ Guanidinium Carboxylates: Preparation of 3-Carboxyoctahydro-9aH-pyrimidin-9a-ylium Chloride
Anne-Laure Grillot and David. J. Hart*
*Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, U.S.A.
Abstract
The title guanidinium carboxylate (2) was prepared from tert-butyl 2-bromomethylacrylate (3) using an 11-reaction sequence in 12% overall yield. Sequential addition of two differentiated amino groups to the starting acrylate played a key role in the synthesis.
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■ Syntheses of meso-Azachlorins and meso-Azabacteriochlorins
Kevin R. Gerzevske, Ravindra K. Pandey, and Kevin M. Smith*
*Department of Chemistry, University of California, One Shields Ave., Davis, CA 95616, U.S.A.
Abstract
Starting from azaporphyrins, new classes of chlorins and bacteriochlorins are synthesized using Diels-Alder or osmium tetraoxide reactions. Their strong absorption at long wavelength and easy synthesis suggests they may be promising potential candidates as sensitizers for use in photodynamic therapy of neoplasms.
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■ A Formal Synthesis of Naucléfine
Rahul Vohra and David B. MacLean*
*Department of Chemistry, McMaster University Hamilton, Ontario, L8S 4M1, Canada
Abstract
The amidine (2) has been prepared in three steps from the enolate of (3-cyanopyridin-4-yl)acetaldehyde and tryptamine hydrochloride by way of the enamine (5) and the 1,2,3,4-tetrahydro-β-carboline (6). The conversion of 2 into naucléfine has been previously reported.
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■ Investigations on the Chemistry of Berbanes 14. A Novel Stereoselective Approach to Biologically Active allo-Berbane Derivatives
Gábor Dörnyei, Csaba Szántay,* and Lajos Szabó
*Central Research Institute for Chemistry, Hungarian Academy of Sciences, H-1025 Budapest, P.O.Box 17, Hungary
Abstract
Stereoselective total synthesis of α2 adrenoceptor agents (1) and (2) with allo-berbane skeleton has been performed via Knoevenagel-type condensation of ketones (3).
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■ Induction of the Secondary Metabolism in Catharanthus roseus Cell Suspension Cultures in Response to UV Irradiation and the Addition of a Benzoic Acid Derivative
Paulo R. H. Moreno, Robert van der Heijden, and Robert Verpoorte*
*Leiden/Amsteerdam Center For Drug Research, Division of Pharmacognosy, Gorlaeus Laboratories, Leiden University, Einsteinweg 55/P.O.Box9502 2300 RA Leiden, The Netherland
Abstract
The effects of uv and 2,3-dihydroxybenzoic acid (DHBA) on the secondary metabolism of Catharanthus roseus cell suspension cultures were studied. Uv treatment stopped growth and increased phenylalanine ammonia lyase (PAL) activity, decreased geraniol-10-hydroxylase (G10H) activity and inhibited of strictosidine accumulation. Tryptamine accumulation was not affected by uv. DHBA did not affect the culture growth, but induced anthranilate synthase (AS) and strictosidine synthase (SSS) activity. Tryptophan decarboxylase (TDC) activity was only slightly induced. Levels of tryptamine were higher and strictosidine levels lower than in controls. The combined treatment with uv and DHBA caused a decrease of biomass accumulation. It strongly induced AS, TDC, SSS and PAL. Tryptamine accumulation was strongly induced, and G10H was strongly inhibited. Strictosidine was thus rapidly depleted. The effects of the combined treatment might be due to the formation of a toxic compound from DHBA after uv irradiation.
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■ An Efficient Route to Chiral Benzooxabicyclo[3.2.1]octane Ring System– The First Enantiocontrolled Total Synthesis of (-)-Filiformin
Hideo Nemoto, Hideki Hakamata, Masatoshi Nagamochi, and Keiichiro Fukumoto*
*Pharnaceutical Institute, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan
Abstract
The first enantiocontrolled total synthesis of (-)-filiformin (1) was achieved by the cyclization of phenolic allyl alcohol (5) to give benzooxabicyclo[3.2.1]octane (6) as a key process.
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■ On the Duality of Mechanism of Ring Contraction iv Vitamin B12 Biosysthesis
A. Ian Scott*
*Center for Biological NMR, Department of Chemistry, Texas A & M University, College Station, Texas 77843-3255, U.S.A.
Abstract
A proposal is made for the role of cobalt in the ring contraction and oxygen exchange mechanisms for vitamin B12 biosynthesis in anaerobic bacteria.
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■ Mass Spectral Fragmentation of Orellanine and Its Tetramethyl Ether with Regard to Their Facile Thermal and Photochemical Deoxygenation
Wieslaw Z. Antkowiak,* Róza Antkowiak, Elzbieta Wyrzykiewicz, and Grzegorz Czerwinski
*Facluty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznán, Poland
Abstract
The Elms fragmentation of orellanine, its tetramethyl ether, and orelline were investigated. Fragmentation pathways, the elucidation of which was assisted by accurate mass measurements and metastable transitions, are proposed. A mechanism of the facile N-oxide oxygen elimination as ˙OH or ˙OCH3 found to be a primary process is discussed.
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■ Steric Requirements and High Pressure Influence on the Thermal Deoxygenation of N-Oxides of Orellanine-like Structure
Róza Antkowiak, Wieslaw Z. Antkowiak,* Izabela Banczyk, Grzegorz Czerwinski, Janusz Jurczak, Jerzy Raczko, and Piotr Salanski
*Facluty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznán, Poland
Abstract
5-Hydroxy-9,10-dihydro-4-azaphenanthrene-N-oxide (1) and its methyl ether (2) were found to undergo the facile thermally induced N-oxide oxygen elimination characteristic for the orellanine-like structures. The relationship between the conformation of the N-oxides, the functional group being part of an oximinopropenoxy system, and the deoxygenation temperature requirements is discussed. The significant decrease of the deoxygenation temperature caused by the pressure of 12 kbar in the case of 2 is supposed to indicate the concerted character of the transformation.
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■ Chiral β-Lactams as Synthons. Stereospecific Synthesis of a 6-epi-Lincosamine Derivative
Ajay K. Bose,* Chandra Mathur, Dilip R. Wagle, Raza Naqvi, Maghar S. Manhas, and Zofia Urbanczyk-Lipkowska
*Department of Chemistry and Chemical Engineering, Stevens Institute of Technology, Castle Point on the Hudson Hoboken, NJ 07030, U.S.A.
Abstract
A derivative of 6-epi-lincosamine has been prepared by a sequence of stereospecific steps from an optically active, cis-α-hydroxy-β-lactam. This β-lactam was obtained by an enantiospecific cycloaddition reaction between methoxyacetyl chloride, triethylamine and a Schiff base derived from benzylamine and an optically active aldehyde derived from D-galactopyranose.
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■ Preparation of Spirocyclic Polyethers by Intramolecular Heck Reactions
Steven D. Knight and Larry E. Overman*
*Department of Chemistry, University of California, Irvine, California 92717-2025, U.S.A.
Abstract
The first examples of forming spirocyclic polyethers by multiple Heck cyclizations are reported.
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■ First Total Synthesis of Korupensamines A and B
Gerhard Bringmann,* Roland Götz, Paul A. Keller, Rainer Walter, Petra Henschel, Manuela Schäffer, Michaela Stäblein, T. Ross Kelly, and Michael R. Boyd
*Institüte of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany
Abstract
The first total synthesis of korupensamines A (1a) and B (1b), highly polar naphthylisoquinoline alkaloids and, simultaneously, ‘mono-meric building blocks’ of the michellamines, is described. Key step is the PdII catalyzed intermolecular biaryl coupling of the two appropriately protected naphthalene and isoquinoline moieties (10) and (11), with the coupling positions activated by bromine and trialkylstannane substituents respectively.
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■ HIV Reverse Transcriptase Inhibitors: A Concise Ene Reaction Based Synthesis of the 7,8-Dihydro-6H,12H-azepino[2,1-b]quinazoline System, and Its Reaction with Nitrile Oxides
Catharine Goulaouic-Dubois, David R. Adams, Angele Chiaroni, Claude Riche, Frank W. Fowler,* and David S. Grierson*
*Department of Chemistry, State University of New York ar Stony Brook, Stony Brook, New York 11794-3400, U.S.A.
Abstract
The reaction of amide (5), obtained in two steps from 2-amino benzophenone (4) with triflic anhydride, followed by treatment of the in situ generated imodyl triflate (7) with LiCN led to exclusive formation of the tetrahydroquinazoline (10). Thermolysis of this intermediate promoted an ene reaction leading to the azepino-quinazoline (11) (63% yield). The 1,3-dipolar cycloaddition between this product and nitrile oxide (12) proved chemoselective, producing the novel pentacyclic oxadiazine (14) as a 7:3 mixture of diastereomers in 79% yield.
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■ An Asymmetric Synthesis of S-(-)-Norznicanine
Albert I. Meyers* and Thanh H. Nguyen
*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.
Abstract
The absolute configuration of the titled natural alkaloid has been confirmed as R-(+) through a chiral formamidine-assisted total synthesis.
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■ Total Synthesis of Racemic Physostigmine, Physovenine and Its Sulfur Analogue by the Oxindole-5-O-tetrahydropyranyl Ether Route
Qian-sheng Yu, Bao-yuan Lu, and Xue-Feng Pei*
*Department of Chemistry, Georgetown University, Washington DC 20057, USA
Abstract
1,3-Dimethyl-5-tetrahydropyranyloxyoxindole (4) was synthesized from 4-methylaminophenol sulfate (metol) (1). Phase transfer catalyzed C3-alkylation of compound (4) produced alcohol (5), nitrile (8), and thioalcohol (13) after treatment of bromide (12) with thiourea. Compound (5) and (13) were converted into racemic physovenine (7) and thiaphysovenine (15) by reaction with LAH, in situ deprotection, and reaction of phenols with methyl isocyanate. Conversion of nitrile (8) into racemic physostigmine (11) which included a reductive N-methylation of 9 was similarly accomplished.
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■ A Microbial Lipase Based Stereoselective Synthesis of (d)-α-Tocopherol from (R)-Citronellal and (S)-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-yl)acetic Acid
David L. Coffen,* Noal Cohen, Anthony M. Pico, Rudolph Schmid, Mark J. Sebastian, and Frederick Wong
*Roche Research Center Hoffmann-La roche, Inc., Nutley, New Jersey 07110, U.S.A.
Abstract
A new synthesis of natural vitamin E (2R,4’R,8’R)-α-tocopherol) based on (R)-citronellal and (S)-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)acetic described. The citronellal is elaborated into an optically pure C13 allylic carbonate using a lipase catalyzed kinetic resolution to control the new chiral center. Palladium catalyzed coupling of this C13 carbonate with either a β-ketoester or β-ketosulphone derived from the chromanylacetic acid completes the assembly of the α-tocopherol skeleton. Appropriate functional group modifications are used to complete the synthesis.
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■ Lipase-catalyzed Resolution of Acetates of Racemic Phenolic Aporphines and Homoaporphines in Organic Solvent
Osamu Hoshino,* Hiroyuki Fuchino, and Masafumi Kikuchi
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
Abstract
Enzymatic resolution of (±)-1-acetoxy-2,9,10-trimethoxyaporphine (O-acetylthaliporphine)(3), (±)-2-acetoxy-1,9,10-trimethoxyaporphine (O-acetylpredicentrine)(4), and (±)-3-acetoxy-2,9,10-trimethoxyaporphines (5) by use of immobilized lipase in organic solvent gave resolved 3-5 and the corresponding hydroxyaporphines (9-11) in fair to good chemical and optical yields. Analogous reaction of (±)-1-acetoxy-2,10,11-trimethoxyhomoaporphine (6) did not take place, whereas that of (±)-2-acetoxy-1,10,11-trimethoxy- and (±)-3-acetoxy-2,10,11-trimethoxyhomoaporphines (7 and 8) produced optical active 7, 8 and hydroxyhomoaporphines (13, 14).
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■ Unsaturated Fatty Acid Lactones from the Fungus Ophiostoma piliferum
William A. Ayer* and Abdul Q. Khan
*Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
Abstract
Three new hydroxylated lactones piliferolide A, B, and C (3-5), derived from oleic and palmitic acid have been isolated from liquid cultures of Ophiostoma piliferum, a fungus associated with aspen. Their structures, including absolute configuration, have been determined from spectroscopic data and by chemical studies.
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■ Conformational States of Indolactams. Structures of 13-N-Desmethylidolactam-V and 13-O-Indolactam-V
Yasuyuki Endo,* Takashi Imada, Kentaro Yamaguchi, and Koichi Shudo
*Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan
Abstract
Tumor-promoting teleocidins are known to exist in an equilibrium between two conformational states, the twist and the sofa form, in solution. 13-O-Indolactam-V, takes the fold form in solution and in the crystal, indicating that the conformation of the nine-membered lactam ring of indolactams is influenced by the nature of the group at position 13.
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■ A Photochemical Synthesis of Benz[d]indeno[1,2-b]azepines
Jesús Fidalgo, Luis Castedo,* and Domingo Domínguez*
*Departamento de Química Orgánica, Facultad de Química, Universidad de Santiago y Sección de Alcaloides del C.S.I.C., 15706 Santiago de Compostela, Spain
Abstract
A novel synthesis of benz[d]indeno[1,2-b]azepine (10) has been achieved by photochemical cyclization of the bromo enaminone (8). On the other hand, irradiation of enolates and enamides failed to give the cyclized azepines.
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■ Synthesis of Optically Pure 1,4-Dihydropyridine Derivatives by Means of Diastereoisomeric Separation of the Hantzsch Intermediates Bearing (R)-1-Phenylethylamino Group
Yoshiyuki Kosugi,* Masanori Hori, and Tatsuo Nagasaka
*Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Hantzsch intermediates, which were obtained by Michael addition reaction of benzylideneacetoacetates with the enamino esters bearing (R)-1-phenylethylamino group as a chiral auxiliary, were separated into two diastereoisomeric mixtures. Each of them underwent cyclization reaction to give optically pure 1,4-dihydropyridine derivatives.
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■ Studies on the Novel Cyclodepsipeptides. A Total Synthesis of (+)-Jasplakinolide (Jaspamide)
Yoshiro Hirai, Katsuyuki Yokota, and Takefumi Momose*
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
Diastereocontrolled total synthesis of (+)-jasplakinolide (1) has been accomplished via coupling of the tetrapropionate-derived segment (9) with the tripeptide (10) followed by trichlorobenzoyl chloride-mediated macrolactonization.
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■ A Convenient Synthesis of a Simple Coumarin from Salicylaldehyde and Witting Reagent (I): A Synthesis of Methoxy- and Hydroxycoumarins
Takashi Harayama,* Keiko Katsuno, Hiromi Nishioka, Masako Fujii, Yoshitaka Nishita, Hisashi Isii, and Yasuko Kaneko
*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
Reaction of methoxy- and hydroxysalicylaldehydes (1) with phosphorane in diethylaniline under reflux gave only coumarins (3) in high yields except for 3-methoxysalicylaldehyde (1b). It was clarified that methoxy group(s) at C4 and C6 on 1 facilitated the formation of 3.
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■ The Reaction of a Benzotriazole Substituted Vinamidium Salt with Grignard Reagents
Scott A. Petrich, A. Denise Main, Robin Jaeger, Stanton Q. Smith, Fred A. Hicks, John T. Gupton,* James A. Sikorski,* Alan R. Katritzsky,* and Lyle Castle
*Department of Chemistry, University of Central Florida, Orlando, Florida 32816, U.S.A.
Abstract
The reaction of a 2-(1-benzotriazolyl)vinamidinium salt with Grignard reagents to yield α,β-unsaturated aldehydes with stereochemical control is described.
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■ Synthesis of Tris- and Tetrakis(tropocoronand)s Having Short Linker Chains
Kimio Shindo,* Hidetsugu Wakabayashi, Luo-Cheng Zhang, Sumio Ishikawa, and Tatsuo Nozoe
*Department of Chemistry, Faculty of Science, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
Abstract
The syntheses of tris- and tetrakis(tropocoronand)s, a new kind of macrocycles derived from three or four aminotropone imine moieties bridged by three or four short methylene linker chains are described. These tropocoronands were prepared by the reaction of bis(2-methoxytropone imine)salts with α,ω-alkanediamine using a template or with tropopodand derived from benzo[b]cyclohepta[e][1,4]oxazine with N-acetyl-1,2-ethanediamine by an intermolecular heterocycle exchange reaction.
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■ Diastereofacial Additions to a β-Substituted Glycal, Anhydrodihydroartemisinin
Yu Ming Pu and Herman Ziffer*
*National Institute of Health, 9000 Rockville Pike Bethesda, MD 20892-0815, U.S.A.
Abstract
Triphenylphosphine hydrobromide catalyzed electrophilic addition of ethanol to the carbon-carbon double bond of anhydrodihydroartemisinin occurs predominately from the β-face of the molecule.
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■ Synthetic Approaches towards Mitomycins: Synthesis of the Decarbamoyloxymitomycin Derivative
Yoshio Ban,* Shigekazu Nakajima, Kiyoshi Yoshida, Miwako Mori, Masakatsu Shibazaki,* and Tadamasa Date
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
The benzazocine derivative (2) obtained by the criss-cross annulation reaction has been successfully converted to the decarbamoyloxymitomycin derivative (1) in a highly regio and stereocontrolled manner.
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■ Digitalis-like Compounds of Toad Bile: Sulfation and Reduction of Bufadienolides Decrease Potency of Na+, K+- ATPase Inhibition
Shoei-sheng Lee, Fadila Derguini, Reimar C. Bruening, Koji Nakanishi,* Earl T. Wallick, Toshifumi Akizawa, Caryn S. Rosenbaum, and Vincent P. Butler, Jr.
*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.
Abstract
The most abundant digitalis-like compound in the bile of the toad, Bufo marinus, was identified as 12β-hydroxytetrahydroresibufogenin-3-sulfate. Other digitalis-like compounds in toad bile had the properties of bufadienolide-3-sulfates, the most abundant of which was found to be marinobufagin-3-sulfate, a compound previously described only as a trace component in toad skin. Both compounds were less effective than unconjugated marinobufagin in the inhibition of Na+,K+-ATPase enzymatic activity and of Na+,K+-ATPase ouabain binding. This study suggests that sulfation of the A ring and reduction of the lactone ring may be responsible for bufadienolide inactivation in vivo.
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■ Phenolic Compounds in Erythrina x bidwilli and Their Activity Against Oral Microbial Organisms
Munekazu Iinuma,* Yasutoshi Okawa, Toshiyuki Tanaka, Yasuko Kobayashi, and Ken-ichi Miyauchi
*Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
The bioassay-directed fractionation of an acetone extract of the root bark of Erythrina x bidwillii which shows a significant antibacterial activity against oral bacteria led to isolate three new phenolic compounds (bidwillols A and B, and bidwillon C) and a known pterocarpene (erycristagallin), the structures of which were characterized by spectral and physical properties. Among them, erycristagallin showed potent microbial activity against Streptococcus mutans, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.