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
Edward C. Taylor's Special Issues, Vol. 35, No. 2, 1993
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■ Formation and Reaction of p-Quinol Acetates of N-Trifluoroacetyltetrahydroisoqunolin-7-ols
Osamu Hoshino,* Hiromichi Ogasawara, Minoru Arasawa, Masaji Suzuki, and Kazuaki Iizima
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12, Ichigaya Funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
Abstract
Lead tetraacetate oxidation of N-trifluoroacetyltetrahydroisoquinolin-7-ols (13a, b) in AcOH gave stable p-quinol acetates (17a, b). Reaction of 17 with trifluoroacetic acid in CH2CI2 or MeCN gave morphinandienones (15) and aporphines (16), respectively. In contrast with o-quinol acetates (14), it was found that reaction of p-quinol acetates (17) in MeCN was considerably slower than that in CH2Cl2. A mechanistic pathway on the reaction is deduced.
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■ Synthesis of Indole Glycosinolates, Sugar Variants of Naturally Occurring Glucobrassicin
Christian Gardart, Alain Quinsac, Benoît Joseph, and Patrick Rollin*
*Laboratoire de Chimie Bioorganique et Analytique, Université d'Orléans, BP 6759, Rue de Chartres, 45067 Orleans Cedex 2, France
Abstract
Eight sugar-variants (3c-10d) of naturally ocurring glucobrassicin (2c) were synthesized via nucleophilic addition of glycosyl mercaptans on a common nitrile-oxide intermediate.
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■ Photo-oxidative Cleavage of a Furan-Azetidinone Carbon-Carbon Bond: A Synthesis of 4-Acetoxyazetidinone
Joseph E. Lynch,* William L. Laswell, Ralph P. Volante, Robert A. Reamer, David M. Tschaen, and Ichiro Shinkai
*Process Research, Merck Research Laboratories, Division of Merck & Co., Inc., P.O.Box 2000 Rahway, NJ 07065, U.S.A.
Abstract
A stereoselective synthesis of the 4-acetoxyazetidinione (1) from methyl 3(R)-hydroxybutyrate is reported. The synthesis involved stereoselective preparation of a 4-(2-furanyl)azetidinone that was allowed to react with singlet oxygen. The resulting endoperoxide intermediates underwent direct rearrangement to an acyloxyazetidinone that on reaction with sodium acetate gave 1 in modest yield. An improved yield of 1 was obtained by treatment of the endoperoxides with hydrogen peroxide followed by acetic anhydride to give an α-alkoxy acylperoxide that underwent thermal rearrangement to 1.
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■ BF3ÅEOEt2 Catalyzed [4+2] Cycloaddition Reactions of N-Aryl Schiff's Bases with 1-Alkenyl, 1,2-Propadienyl, and 1-Alkynyl Sulfides
Koichi Narasaka* and Takanori Shibata
*Department of Chemistry, Faculty of Science,University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
Abstract
[4+2] Cycloaddition reaction proceeds between N-aryl Schiff’s bases and 1-alkenyl sulfides, a 1,2-propadienyl sulfide, or 1-alkynyl sulfides in the presence of BF3·OEt2 to provide 2-substituted quinoline derivatives. A 2-alkyl-4-quinolone alkaloid, leptomerine, is prepared by applying the present cycloaddition reaction.
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■ Pyrimido[4,5-d]pyrimidines, Pyrimido[4',5':4,5]pyrimido[6,1-a]azepines, and an Imidazo[5,1-f][1,2,4]triazine by Three Component Reaction
Heinrich Wamhoff* and Andreas Schmidt
*Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, D-5300 Bonn 1, Germany
Abstract
Recent examples of the three component reaction: iminophosphoranes / isocyanates / heteroarenes (imines) are described. The uracil (1) affords with O-methyl-ε-caprolactim ether and isocyanates the pyrimido[4’,5’:4,5]pyrimido[6,1-a]azepines (6a-c) and with benzylideneaniline (8) the pyrimido[4,5-d]pyrimidines (9a-d), while azodicarboxylate gives the isofervenuline, pyrimido[4,5-e][1,2,4]triazine (11). Furthermore, pyrimido[4,5-d]pyrimidine (15) is obtained via 14 from 1, N-phenylbenzimidoyl chloride (13), and phenylisocyanate, while the tautomeric mixture 17A € 17B results from treatment of 6-aminouracil (16) with 13; interception with dimethyl acetylenedicarboxylate gives the pyrido[2,3-d]pyrimidine (19).
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■ Synthesis and Resolution of Bis- and Tris-(benzimidazol-1-yl)methanes
Vladimir Bobosík,* Concepción López, Rosa María Claramunt, Chiristian Roussel, Jean Louis Stein, Dominique Thiery, and José Elguero
*Departamento de Química Orgánica y Biología, Faclutade de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain
Abstract
Bis- and tris-(benzimidazol-1-yl)methane derivatives are reported with different substituents at position 2 of the benzimidazole ring. When the substituents are large enough, these compounds, even the bis-derivatives, can be resolved using hplc on CHIRALPAK OT(+) columns. For some compounds, the racemization barriers have been measured and their steric origin ascertained (δG‡ = a + b MR, MR being the molar refractivity).
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■ Stereochemical Observations in the Synthesis of Novel 1,4,5,9b-Tetrahydro-5-phenyl-2H-azeto[2,1-a]isoquinolin-2-one Derivatives
Samuel O. Nortey, David F. McComsey, and Bruce E. Maryanoff*
*Madical Chemistry Department, R. W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477, U.S.A.
Abstract
Imine (5) reacted with Cl2CHC(O)CI in the presence of Et3N to give β-lactams (7a) and (7b) in a 4:1 ratio. The stereochemistry of cycloadduct (7a) was confirmed by X-ray analysis. Uncyclized intermediates were identified. Reduction of dichloro β-lactam (7a) with Zn/HOAc gave mostly exo monochloride (13a), with high stereoselectivity (10:1 ratio). Reduction of a mixture of exo and endo monochlorides (13a) and (13b) with Zn/HOAc indicated that the more sterically hindered endo chlorine is preferentially attacked. Reduction of (7a) with Bu3SnH gave β-lactam (14a) as the major product.
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■ Cycloaddition Reactions with Azabenzenes, XVIII. Synthesis of [2]Pyrindines
Hans Neunhoeffer,* Bernd Philipp, Brigit Schildhauer, Ralf Eckrich, and Uwe Krichbaum
*Institut für Organische Chemie, Technische Hochschule Darmstadt, Petersenstrasse. 22 D-6100 Darmstadt, Germany
Abstract
The reaction of 1,2,4-triazines (1) and 1-cyclopentenylpyrrolidine (2) afforded 6,7-dihydro-5H-[2]pyrindines (3) in good yields. Oxidation of 3 to the N-oxides (4), reaction of 4 with acetic anhydride to 5-acetoxy-6,7-dihydro-5H-[2]pyrindines (5) and elimination of acetic acid afforded [2]pyrindines (7). 2-Methyl-2H-[2]pyrindines (9) were also prepared.
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■ A Convenient Synthesis of Pyrrole- and N-Aminopyrrole-3-propionate Esters
Peter A. Jacobi* and Guolin Cai
*Hall-Atwater Laboratories, Wesleyan University, Middletown, Connecicut 06459-0180, U.S.A.
Abstract
Trisubstituted pyrroles having a substitution pattern found in many naturally occurring linear and macrocyclic tetrapyrroles have been prepared in a regiospecific fashion by a two step sequence involving Diels-Alder reaction of 2-oxo-3-butenoate esters (58) with 2-alkoxy-1,3-pentadiene derivatives (46), followed by ozonolysis and Paal-Knorr cyclization.
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■ An Improved Procedure for the Preparation of 2,2’-Spirobi[2H-1-benzopyran]
Muthiah Inbasekaran*
*Organic Chemicals and Polymers Laboratry, Central Research and Development, Building 1707, The Dow Chemical Company, Midland, Michigan 48674, U.S.A.
Abstract
A simple and improved procedure for preparing multi-gram quantities of 2,2’-spirobi[2H-1-benzopyran] (2) is reported. The cyclization of the dihydroxybenzopyran intermediate (1) into 2 proceeded smoothly when a solution of 1 in 2-ethoxyethyl acetate was heated under reflux for 3 hours.
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■ The Reactions of o-Quinone Monoimides with Some Thiophenes and Furans
Harold W. Heine,* David K. Williams, Jennifer L. Rutherford, John Ramphal, and Elizabeth A. Williams
*Department of Chemistry, Bucknell University, Lewisburg, PA 17837, U.S.A.
Abstract
o-Quinone monoimides undergo inverse electron demand Diels-Alder reactions with thiophene, 2-alkylated thiophenes, 2- and 2,5-alkylated furans and benzofurans. 2,5-Dimethylthiophenes and 2-methylbenzo[b]thiophene, on the other hand interact with o-quinone monoimides to yield ethers, products arising from hydride abstractions from the methyl groups by the imido nitrogen of 6.
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■ Application of the Intramolecular Schmidt Reaction to the Asymmetric Synthesis of (-)-Indolizidine 209B from Pulegone
Jeffery Aubé,* Pat S. Rafferty, and Gregory L. Milligan
*Department of Medicinal Chemistry, University of Kansas, 4070 Malott Hall, Lawrence, Kansas 66045-2506, U.S.A.
Abstract
A synthesis of enantiomerically pure indolizidine alkaloid 209B, beginning from naturally occurring pulegone, is described. The key step is the formation of a bicyclic lactam via the intramolecular Schmidt reaction of an alkyl azide with a cyclic ketone. The 11-pot synthesis was accomplished in an overall yield of 21.9%.
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■ Squarylium Dyes Based on 2,6-Di-tert-butylselenopyrylium or Telluropyrylium Nuclei
Michael R. Detty* and Bruce Henne
*Office Imaging Research and Technology Development, Eastman Kodak Company, Rochester, New York 14650-2106, U.S.A.
Abstract
The condensation of 2,6-di-tert-butyl-4-methylselenopyrylium and -telluropyrylium salts with squaric acid gives squarylium dyes with absorption maxima at 847 and 910 nm, respectively, in dichloromethane. The condensation of a 2,6-di-tert-butyl-4-ethylselenopyrylium salt with squaric acid gives the corresponding dimethyl-substituted squarylium dye with an absorption maximum at 906 nm in dichloromethane. Electrochemical reduction and oxidation potentials of these dyes are compared to those of the corresponding squarylium dyes based on pyrylium and thiopyrylium nuclei.
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■ Efficient Michael Addition Reactions of the N-Arylsulfonyl-3-phenylthiopiperidones. Synthesis of 3-Substituted Dihydropyrodinones
Masako Nakagawa,* Yasuhiro Torisawa, Toshihiro Hosaka, Kiyoshi Tanabe, Fabrice Tavet, Maki Aikawa, and Tohru Hino*
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Efficient methods for the Michael addition reactions of N-arylsulfonyl-3-phenylthiopiperidones (1) with both the protected amidoacrylates (4,9) and the simple acrylates (12) have been developed. These reactions offer an efficient route to the 3-alkyl-substituted dihydropyridinones (3, 11), the dienophiles employed in the natural product synthesis.
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■ One-Pot Synthesis of Pyrroles from N-Silyl-1-azaallyl Anions
Takeo Konakahara,* Atsuo Watanabe, Kazumi Maehara, Moriyo Nagata, and Marhaba Hojahmat
*Department of Industrial Chemistry, Faculty of Science and Technology, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
Some kinds of pyrroles, 1-pyrrolines, and 2H-pyrroles were synthesized from the N-silyl-1-azaallyl anions and α-diketones by an one-pot reaction.
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■ Mild Preparation of 1-Benzyloxyiminoalkylphosphonic Dichlorides: Application to the Synthesis of Cyclic Phosphonic Diesters and Cyclic Monoester Amides
Richard Neidlein,* Holger Keller, and Roland Boese
*Pharmazeutisch Chemishes Institut, Im Neuenheimer Feld 364, 6900 Heidelberg, Germany
Abstract
1-Benzyloxyiminophosphonates (3) were converted under very mild conditions to the corresponding phosphonyl dichlorides (5). The application toward the synthesis of diastereomeric 1,3,2-oxazaphospholidines (6/7), and diastereomeric 1,3,2-dioxaphosphorinanes (8/9) is reported. The structure of 9a was confirmed by X-ray analysis.
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■ Alkylation of Ambident Nucleophilic Hydroxamates with 4-Substituted 2-Azetidinones: Formation of Bicyclic β-Lactam Intermediates
Margaret J. Stauber, Thèrése Debiak-Krook, and Marvin J. Miller*
*Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, U.S.A.
Abstract
Silver salts of various O-alkylhydroxamic acids react with 4-substituted 2-azetidinones (7) to produce novel substituted β-lactams. N- or O-alkylation of the hydroxamate silver salts can be controlled by reaction conditions, variation of the leaving group (OAc or SEt) of the 4-substituted 2-azetidinone, and the mode of formation of the silver salt itself. Elaboration of the products to azapenems and oxapenams may produce novel β-lactam derivatives for biological evaluation.
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■ Structure of Adducts of 2-Arylaminothiazolines with Isocyanates and Isothiocyanates
Martin Avalos, Reyes Babiano, Pedro Cintas,* José L. Jiménez, Juan C. Palacios, and Concepción Valencia
*Departamento de Química Orgánica, Universidad de Extremadura, Avenida de Elvas s/n, 06071-Badajoz, Spain
Abstract
Extensions of the reaction of 2-chloroethyl isothiocyanate with aliphatic and aromatic amines have been accomplished, and 2-arylamino-2-thiazoline hydrochlorides (5) are easily obtained. Structures attributed initially to the products of condensation of 5 with phenyl isocyanate and phenyl isothiocyanate have been corrected and assigned unequivocally by X-ray analysis. By heating, these molecules do not undergo an endo-N→exo-N’ rearrangement.
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■ 2-Keto Sugars as Preformed Heterocyclic Building Blocks. Synthetic Studies
Andrew M. Griffin, Nicholas J. Newcombe, David Alker, Michael V. J. Ramsay, and Timothy Gallagher*
*School of Chemistry, University of Bristol, BS8 1TS, U.K.
Abstract
The synthesis of a series of bicyclic 2-hexulose derivatives (5), (6) and (7), which provide access to regiospecific carbohydrate-based ketone enolates, is described. The preparation of silyl enol ethers (21) and (22) from keto ether (5) and keto acetal (6), respectively, is also reported.
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■ Prerparation of 1-Dimethyaminomethylene-3-alkenylindoles
Brian E. Love* and Prasad S. Raje
*Department of Chemistry, Auburn University, Extension Cottage-59 Duggar Drive Alabamaa 36849-5319, U.S.A.
Abstract
A one-pot synthesis of 1-dimethylaminomethylene-3-acylindoles is described, as well as their conversion to the corresponding 3-alkenylindoles.
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■ Synthesis and Reaction of 1-Phenyl-4-trimethylstannyl-1,2,3-triazoles
Takao Sakamoto, Daishi Uchiyama, Yoshinori Kondo, and Hiroshi Yamanaka*
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
1,3-Dipolar cycloaddition reaction of trimethylstannylacetylene with phenyl azide gave a regioselective product, 1-phenyl-4-trimethylstannyl-1,2,3-triazole. On the other hand, the reaction of trimethylstannyl-1-hexyne, -phenylacetylene, and -trimethylsilylacetylene with the azide yielded a mixture of the corresponding 4- and 5-trimethylstannyl-1-phenyl-1,2,3-triazoles. Detrimethylstannylation, iodination, benzoylation, and palladium-catalyzed phenylation of 4-trimethylstannyl- and 4,5-bis(trimethylstannyl)-1-phenyl-1,2,3-triazoles were also described.
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■ Approach to the Synthesis of Astechrome
Hao Jing, Yutaka Aoyagi, and Akihiro Ohta*
*Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
The coupling reaction between 2-chloro-6-chloromethyl-5-methoxy-3-methylpyrazine 1-oxide and indolylmagnesium bromide gave 2-chloro-6-(indol-3-yl)methyl-5-methoxy-3-methylpyrazine 1-oxide, which was converted to a hydroxamic acid derivative via an indoline. The synthesis of 2-hydroxy-6-(indol-3-yl)methyl-5-methoxy-3-methylpyrazine 1-oxide, constituting the skeleton of astechrome, was accomplished from the Fe salt of the corresponding indolinehydroxamic acid derivative by oxidation with bis(salicylidene)ethylenediaminato cobalt(II) [Co(Salen)].
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■ Multisubstrate Analogue Inhibitors of Glycinamide Ribonucleotide Transformylase Based on 5-Deazaacyclo Tetrahudrofolate (5-DACTHF)
Eric C. Bigham,* W. Revill Mallory, Steven J. Hodson, David S. Duch, Robert Ferone, and Gary K. Smith
*Wellcome Research Laboratories, Burroughs Wellcome Co., 3030 Cornwallis Road, Research Triangle Park, NC 27709, U.S.A.
Abstract
N10-Substituted acetyl derivatives of 5-DACTHF are less active in general than the parent. However, multisubstrate analogue inhibitors that are 1000-fold more potent were synthesized, and N10-pyruvoyl-5-DACTHF serves as a precursor for a metabolically assembled multisubstrate analogue.
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■ Synthesis of Fluorine Analogs of Hematoporphyrin
Akira Ando, Tamotsu Kitamura, Seiji Aono, Hidenobu Sato, Masaaki Omote, Mayumi Koyama, Toshiyuki Takagi, Takuichi Miki, Itsumaro Kumadaki,* and Haruo Sato
*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan
Abstract
With the aim of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorine analogs of hematoporphyrin, which had trifluorohydroxyethyl group(s) in the place of hydroxyethyl groups, were synthesized by the reaction of deuteroporphyrin dimethyl ester with trifluoroacetaldehyde in the presence of aluminum chloride. Preliminary results of biological tests of the products showed that the hexafluoro analog of hematoporphyrin accumulates to Human liver cancer cells more selectively than other fluorine analogs.
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■ Direct Amination of 3(2H)-Pyridazinones: Re-investigation of the Reaction of 3,6-Dimethoxypyridazine with Hydrazine
William J. Coates* and Alexander McKillop
*Medical Chemistry, SmithKline Beecham Pharmacuticals, The Frythe, Welwyn, Hertfordshire, AL6 9AR, U.K.
Abstract
3,6-Dimethoxypyridazine has been shown to react with hydrazine via 4-amination of 6-methoxy and 6-hydrazino-3(2H)-pyridazinones to give 4-amino-6-methoxy- and 4-amino-6-hydrazino-3(2H)-pyridazinones, and not the corresponding 5-amino isomers as previously reported. The published synthesis of the 5-amino isomers, used to confirm the earlier findings, is incorrect as regards 5-amino-6-hydrazino-3(2H)-pyridazinone, which has been prepared by an alternative route. The 4-amination reaction has also been extended to 6-chloro-3(2H)-pyridazinone.
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■ Reaction of Methyl 2-Bensoylamino-3-dimethylaminopropenoate with Heterocycilc Hydroxy Compounds. The Synthesis of Fused Pyranoazines
Matej Kmetic, Branko Stanovnic,* Miha Tisler, and Thomas Kappe
*Department of Chemistry, University of Ljubljana, Murnikova 6, P. O. Box537, 61000 Ljubljana, Slovenia
Abstract
Methyl 2-benzoylamino-3-dimethylaminopropenoate (1) reacts in acetic acid with monocyclic or bicyclic heterocyclic compounds with two hydroxy or potential hydroxy groups in 1,3-position to give fused pyranones. Accordingly, derivatives of 2H-pyrano[3,2-c]pyridine (3), 2H-pyrano[3,2-c]quinoline (9,10, and 11), 2H-pyrano[2,3-d]pyridazine (13) , 8H-pyrano[3,2-d]tetrazolo[1,5-b]pyridazine (16) , pyrano[4,3-b]pyran (18) , and 2H-pyrano[2,3-c]pyridine (22) were obtained.
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■ Components of the Bark of Artocarpus rigida BL.2. Structures of Four New Isoprenylated Flavone Derivatives Artonins M, N, O and P
Yoshio Hano, Ryohei Inami, and Taro Nomura*
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Four new isoprenylated flavone derivatives, artonins M (1), N (2), O (3), and P (4), were isolated from the bark of Artocarpus rigida Bl., an Indonesian moraceous plant. The structures of artonins M, N, O, and P were determined to be formulae 1, 2, 3, and 4, respectively, on the basis of spectroscopic studies and chemical evidence.
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■ Synthesis of an Orally Active PAF Antagonist of the N-[4-(3-Pyridinyl)butyl]pentqdienamide Class
Percy S. Manchand,* Alan Schwartz,* Steven Wolff,* Peter S. Belica, Pradeep Madan, Paresh Patel, and Sandra J. Saposnik
*Roche Research Center, Hoffman-La Roghe Inc., Nutley, New Jersey 07110, U.S.A.
Abstract
The PAF antagonist [R-(E,E)]-5-(4-methoxyphenyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-2,4-decadienamide (2) was synthesized from (S)-α-methyl-3-pyridinebutanol (14), which was obtained either from ethyl lactate or by enantioselective kinetic hydrolysis of its racemate using the lipase derived from Pseudomonas cepacia (syn. P. fluorescens). Mesylation of 14, followed by azide displacement and hydrogenation, produced amine (7), which was coupled with the p-nitrophenol ester (8) to give 2. The direct coupling of (E,E)-5-(4-methoxyphenyl)-2,4-decadienoic acid (27) with azide (24) in the presence of tri-n-butylphosphine also gave 2. Acid (27) was prepared by a vinylogous Reformatsky reaction between ketone (25) and methyl 4-bromocrotonate.
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■ Hydrogen Bond Directed Nitrile Oxide Cycloaddition Reactions of Allylic 2°-Amides
Dennis P. Curran,* Scott A. Gothe, and Sung-Mo Choi
*Department of Chemistry, University of Pittsburgh, Parkman Avenue & University Drive, Pittsburgh, PA 15260, U.S.A.
Abstract
The ability of allylic and homoallylic 2°-amides to direct nitrile oxide cycloaddition reactions has been studied. For N-cyclopentenyl amides, good regio- and stereochemical control are observed and mechanistic studies suggest that hydrogen bonding in the transition state selectively accelerates formation of one isomer. Acyclic allylic and homoallylic 2°-amides do not exhibit high regio- or stereoselectivity.
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■ Fused Pyrimidines. Part 5. Pyrimido[4,5-d]pyrimidine Analogues of Folic Acid
Thomas. J. Delia,* Markus Baumann, and Amy Bunker
*Malcom H. Filson Laboratories, Department of Chemistry, Central Michigan University, Mt. Pleaasant, MI 48859, U.S.A.
Abstract
Pyrimido[4,5-d]pyrimidine analogues of folic acid have been prepared and tested for antitumor activity. Using Mannich reaction conditions, 2,4,6-triaminopyrimidine (12) or 2,4-diamino-6-oxopyrimidine (13) was treated with formaldehyde and either diethyl N-[4-(2-aminoethyl)benzoyl]-L-glutamate (18) or diethyl N-[4-(3-aminopropyl)benzoyl]-L-glutamate (24). The corresponding diester products (19, 20 and 25, 26) were converted to the diacids (5,6 and 7,8) by treatment with aqueous ethanolic sodium hydroxide. Compounds(5,6, and 7) were screened against CCRF-CEM leukemic cells and found to be significantly less active than DDATHF, one of the most active compounds for this system.