Special Issue

Arnold Brossi's Special Issues, Vol. 39, No. 2, 1994

48 data found. 31 - 48 listedFirst Previous
Paper | Special issue | Vol 39, No. 2, 1994, pp. 693 - 721
Published online:
DOI: 10.3987/COM-94-S(B)61
New Tetracyclic Derivatives of Imidazo[1,5-a][1,4]benzodiazepines and of Imidazo[1,5-a]-thieno[3,2-f][1,4]-diazepines

Max Gerecke,* Emilio Kyburz, René Borer, and Walter Gassner

*Pharma Division, Preclinical Research, F.Hoffmann-La Roche Ltd., CH-4002 Basel, Switzerland

Abstract

The synthesis of new tetracyclic 1,4-diazepine derivatives is described. In these compounds, an additional five-membered heterocycle is fused on the known tricyclic ring systems imidazo[1,5-a][1,4]benzodiazepine and imidazo[1,5-a]thieno[3,2-f][1,4]diazepine. Many of these new compounds display a very high affinity to the benzodiazepine receptor in mammals.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 723 - 728
Published online:
DOI: 10.3987/COM-94-S(B)63
Diels-Alder Cycloaddition Using Phenyl-2(1H)-pyridones as Dienes

Hiroto Nakano, Takaaki Kato, Hiroshi Tomisawa, and Hiroshi Hongo*

*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

Diels-Alder cycloadditions of 1-methyl-2(1H)-pyridones (1a-d) having a phenyl group in the ring with maleic anhydride (2) or N -phenylmaleimide (3) under atmospheric pressure conditions and with 3 under high pressure conditions were carried out. The reactions of 1a-d with 3 under 10 kbar at 110°C for 72 h gave a mixture of the endo and exo adducts (5 and 6), some of which were unobtainable under atmospheric pressure conditions.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 729 - 739
Published online:
DOI: 10.3987/COM-94-S(B)65
Incorporation of Molecular Nitrogen into Organic Compounds. Titanium Catalyzed Nitrogenation

Miwako Mori,* Mami Kawaguchi, Masanori Hori, and Shin-ichi Hamaoka

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

Abstract

Incorporation of molecular nitrogen into organic compounds was realized using a catalytic amount of TiCl4 in the presence of excess TMSCl and Li. Various imides were prepared from the corresponding acid anhydrides by use of this catalytic system.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 741 - 749
Published online:
DOI: 10.3987/COM-94-S(B)69
Isoacetogenins, Artifacts Issued from Translactonization from Annonaceous Acetogenins

Philippe Duret, Alain Laurens, Reynald Hocquemiller, Diego Cortes, and André Cavé*

*Laboratoire de Pharmacognosie, URA 1843 CNRS(BIOCIS), Faculte de Pharmacie, Université Paris XI, 92296 Chatenay-Malabry Cedex, France

Abstract

Extraction of isoacetogenins from Annona cherimolia roots led us to consider these compounds as artifacts obtained by translactonization of 4-hydroxyacetogenins. To confirm this hypothesis, extraction and characterization of initial acetogenins from fresh crude material and effect of alkaloids, basic medium, and alcohol on the kinetic of the translactonization are performed. A mechanism is discussed for this reaction. Cytotoxic activities of isoacetogenins and corresponding acetogenins are evaluated.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 751 - 766
Published online:
DOI: 10.3987/COM-94-S(B)70
X-Ray Crystal Structures of Potent Receptor Ligands: Etonitazene, cis-(+)-3-Methylfentanyl, Etorphine, Diprenorphine, and Buprenorphine

Judith L. Flippen-Anderson,* Clifford George, Craing M. Bertha, and Kenner C. Rice*

*Laboratory for the Structure of Matter, Code 6030, Naval Research Laboratory, Washington, DC 20375, U.S.A.

Abstract

As a prelude to molecular modeling and other studies of the newly cloned and expressed μ, δ and k opioid receptor subtypes, X-Ray crystal structures were determined for etonitazene, (1) cis-(+)-3-methylfentanyl (4) and etorphine (6), three extremely potent opioid agonists. X-Ray crystal structures were also determined for diprenorphine (7), a potent opioid antagonist, and buprenorphine (8), a clinically useful mixed agonist-antagonist. Agonists (1), (4) and (6) are structurally diverse but have similar profiles while (7) and (8) have substantially different pharmacological profiles but differ structurally by only a methyl vs. a tert-butyl function. The present results should facilitate studies toward understanding the differences which underlie these observations on a molecular basis.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 767 - 778
Published online:
DOI: 10.3987/COM-94-S(B)71
Benzo[H]-1,6-naphthyridine Synthesis via Intramolrcular Diels-Alder Reactions of Aryl Oxazoles: Synthetic Approach to 2-Bromoleptoclinidinone

Michael E. Jung* and Susan M. K. Dansereau

*Department of Chemistry and Biochemistry, University of California, 405 Hilgard Avenue Los Angels, CA 90024, U.S.A.

Abstract

A new route for the synthesis of benzo[h]-1,6-naphthyridines is described. The method involves the intramolecular Diels-Alder cycloaddition of aryl oxazoles with substituted acrylamides to give pyridines and was developed as a route to the antileukemic aromatic alkaloid 2-bromoleptoclinidinone.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 779 - 800
Published online:
DOI: 10.3987/COM-94-S(B)75
Chemistry of Sampangines

Jordan K. Zjawiony,* Anita R. Srivastava, Charles D. Hufford,* and Alice M. Clark

*Department of Pharmacology, School of Pharmacy, University of Mississippi, University, Mississippi 38677, U.S.A.

Abstract

The reactivity of sampangines in electrophilic and nucleophilic substitution reactions, nucleophilic addition reactions and the total synthesis of some derivatives are described. These reactions provide access to many analogs substituted in rings A-, B, C-, and D.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 801 - 809
Published online:
DOI: 10.3987/COM-94-S(B)77
Imidazole-assisted Intramolecular Phenoxythiocarbonylation of Tertiary Alcohols A Key Reaction for the Deoxygenation of α-Trifluoromethylarylmethyl Alcohols

Fu-Lian Hsu,* Xiaoyan Zhang, Seoung-Soo Hong, Frederic J. Berg, and Duane D. Miller

*U.S. Army Edgewood Research, Development & Engineering Center, Aberdeen Proving Ground, Maryland 21010-5423, U.S.A.

Abstract

The deoxygenation of α-trifluoromethylarylmethyl alcohols failed under catalytic hydrogenation conditions. However, these alcohols can be deoxygenated via their thionocarbonate intermediates followed by homolytic reductive cleavage of the C-O bond. The formation of the phenyl thionocarbonate esters is sterically dependent. Consequently, secondary α-trifluoromethyl arylmethyl alcohols can be smoothly converted to thionocarbonates, but tertiary alcohols cannot. Exceptions to this lack of reactivity are the aryl 4-substituted imidazolyl trifluoromethyl carbinols, which do form the thionocarbonates under these conditions.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 811 - 818
Published online:
DOI: 10.3987/COM-94-S(B)81
Chiral 1,2-Dihydropyridines and 2,5-Dihydrophridium Salt Equivalents. Synthesis of (+)-Anatabine and a Chiral Benzomorphane

Yves Génisson, Maryam Mehmandoust, Christian Marazano,* and Bhupesh C. Das

*Institut des Chimie des Substances Naturelles, C.N.R.S., Avenue de la Terrasse, Bat. 27, 91198 Gif-sur-Yvette Cedex, France

Abstract

Sodium borohydride reduction of readily available chiral pyridinium salts (2a-b) in alkaline medium led to 1,2-dihydropyridines (3a-b) which spontaneously cyclized to give 2,5-dihydropyridinium salt equivalents (4a-b). Use of these intermediates for a short synthesis of the tobacco alkaloid (+)-anatabine and of the benzomorphane derivative ((+)-14) is reported.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 819 - 832
Published online:
DOI: 10.3987/COM-94-S(B)82
Synthesis of 2-Fluoro-3-trifluoromethylthiophenes and 3-Trifluoromethylthiophenes from Hexafluoroacetone

Klaus Burger,* Brigitte Helmreich, Vera Ya. Popkova, and Lev S. German

*Department od Organic Chemistry, Technische Universität München, Lichtenbergstrasse 4, D-85747 Garching, Germany

Abstract

The transformation of bis(trifluoromethyl)-1-oxabuta-1,3-dienes (1) — available from hexafluoroacetone — into 2-fluoro-3-trifluoromethylthiophenes (9) via 4,4-difluoro-3-trifluoromethyl-3-buten-1-ones (5) is described. The fluorine atom at skeleton position 2 of the thiophenes (9) is readily displaced by various nucleophiles.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 833 - 845
Published online:
DOI: 10.3987/COM-94-S(B)83
Syntheses of Carprofen, a Carbazole-based Non-steroidal Anti-inflammatory Agent

Percy S. Manchand,* David L. Coffen, Peter S. Belica, Frederick Wong, Harry S. Wong, and (the late) Leo Berger

*Roche Research Center Hoffmann-La roche, Inc., Nutley, New Jersey 07110, U.S.A.

Abstract

Syntheses of carprofen (6) have been achieved by two approaches from carbazole (11). In one, 2,9-diacetylcarbazole (12) and 2-acetylcarbazole (13) were chlorinated with trichloroisocyanuric acid (15) to give the 6-chloro derivatives (16) and (17), respectively. Reduction of 16 with NaBH4, followed by acetylation, cyanide displacement, and hydrolysis afforded 6 in 73% yield from 16. Alternatively, 17 was converted into its trimethylsilyloxy cyanohydrin derivative (27), which was reduced with SnCl2 and hydrolysed to give 6 in 75% yield from 17. In the other approach, the ketone (18), derived by a Friedel-Crafts acylation of 9-acetylcarbazole with 2-chloropropanoyl chloride followed by chlorination with 15, was converted into the hydroxyketal (28) with methanolic NaOMe. Mesylation of 28, followed by a modified Favorskii rearrangement and hydrolysis gave 6 in 73% yield from 18.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 847 - 858
Published online:
DOI: 10.3987/COM-94-S(B)84
Artonins Q, R, S, T, and U, Five New Isoprenylated Phenoles from the Bark of Artocarpus heterophyllus Lamk

Miwa Aida, Kazuki Shinomiya, Kayoko Matsuzawa, Yashio Hano, and Taro Nomura*

*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

Five new isoprenylated phenols, artonins Q (1), R (2), S (3), T (4), and U (5), were isolated from the bark of Artocarpus heterophyllus Lamk., an Indonesian moraceous plant. The structures of artonins Q, R, S, T, and U were shown to be 1, 2, 3, 4, and 5, respectively, on the basis of spectroscopic data and chemical evidence.

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 859 - 866
Published online:
DOI: 10.3987/COM-94-S(B)85
Preliminary Experiments for Asymmetric Total Synthesis of the Thienamycin-like γ-Lactam

Hiroshi Matsunaga, Toshio Kumagai, Yoshinori Inoue, and Yoshimitsu Nagao*

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

Abstract

Optically active bicyclic γ-lactam carboxylates (3 and 4) were readily synthesized by employing chiral 5-alkylated pyrrolidin-2-one (9b) obtained from an asymmetric alkylation with tin(ll) enolate (6a) onto 5-acetoxypyrrolidin-2-one (7b).

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Paper | Special issue | Vol 39, No. 2, 1994, pp. 867 - 877
Published online:
DOI: 10.3987/COM-94-S(B)86
2-Methyl- and 4-Methyl-Δ8-tetrahydrocannabinol: Correlation of Spatial Distinction with Cannabinoid Receptor Binding

Robert Glaser,* Itay Adin, Raphael Machoulam, and Lumir Hanus

*Department of Chemistry, Ben-Gurion University of Negev, Beer-Sheva 84105, Israel

Abstract

A high level of binding to the brain cannabinoid receptor was found for 2-methyl-Δ8-tetrahydrocannabinol (THC) while no binding was observed for 4-methyl-Δ8-THC. Four energy minima were found by molecular mechanics for ethyl side-chain models of Δ8-THC [syn- and antiperiplanar and (±)-orthogonal values for torsion angle C(4)-C(3)-C(α)-C(β)]. The active Δ8-THC and 2-methyl-Δ8-THC molecules share a common structural feature [a relatively low energy synperiplanar value C(4)-C(3)-C(α)-C(β) torsion angle conformation for the n-pentyl side chain] that is not exhibited by the inactive 4-methyl-Δ8-THC analogue. This spatial distinction may represent the basis for the difference in biological activity between the two isomers examined.

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Review | Special issue | Vol 39, No. 2, 1994, pp. 879 - 889
Published online:
DOI: 10.3987/COM-94-S(B)36
Heterocycles in Replication and Assembly

M. Morgan Conn, Edward A. Wintner, and Julius Rebek, Jr.*

*Department of Chemistry, Room 18-390, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, U.S.A.

Abstract

The role of molecular complementarity and self-complementarity in recognition, replication and assembly is reviewed.

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Review | Special issue | Vol 39, No. 2, 1994, pp. 891 - 902
Published online:
DOI: 10.3987/REV-94-SR(B)3
Synthesis of Proaporphine Alkaloids

E.Kyle Stephenson and Michael P. Cava

*Department of Chemistry, The University of Alabama, Box 870336, Tuscaloosa Alabama 35487-0336, U.S.A.

Abstract

The synthesis of proaporphine alkaloids has been reviewed

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Review | Special issue | Vol 39, No. 2, 1994, pp. 903 - 931
Published online:
DOI: 10.3987/REV-94-SR(B)4
Recent Progress in the Enatioselective Synthesis of Isoquinoline Alkaloids

Maria D. Rozwadowska

*Facluty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznán, Poland

Abstract

Recent developments in the enantioselective synthesis of isoquinoline alkaloids are reviewed. They include the enantioselective modification of the traditional methods (Pictet-Spengler, Bischler-Napieralski, Pomeranz-Fritsch) as well as the modern “C-C-connective” approach.

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Review | Special issue | Vol 39, No. 2, 1994, pp. 933 - 955
Published online:
DOI: 10.3987/REV-94-SR(B)5
Molecular and Functional Properties of the Monoamine Oxidases

Creed W. Abell,* Ronald M. Stewart, Paul J. Andrews, and Sau-Wan Kwan

*Division of Medicinal Chemistry, College of Pharmacy and the Institute for Neuroscience, The University of Txas, Austin, Texas 78712-1074, U.S.A.

Abstract

The role of monoamine oxidase A and B in the nervous system and in Parkinson’s disease is reviewed. Recent advances made in the molecular and biochemical properties of MAO A are also discussed, and the putative functional regions within MAO A are identified based on sequence similarities in other proteins.

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48 data found. 31 - 48 listedFirst Previous