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2096
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STEREOSELECTIVE SYNTHESIS OF (-)-CYTOXAZONE AND ITS UNNATURAL CONGENER (+)-5-EPI-CYTOXAZONE
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Department of Chemistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Chemistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Chemistry of Bioactive Natural Products. René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil
Department of Biochemistry and Molecular Biology. Federal University of Viçosa., Viçosa, MG, Brazil
Department of Biochemistry and Molecular Biology. Federal University of Viçosa., Viçosa, MG, Brazil
Department of Chemistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Department of Chemistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Chemistry of Bioactive Natural Products. René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil
Department of Biochemistry and Molecular Biology. Federal University of Viçosa., Viçosa, MG, Brazil
Department of Biochemistry and Molecular Biology. Federal University of Viçosa., Viçosa, MG, Brazil
Department of Chemistry. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil
Abstract
An interesting protocol for stereoselective synthesis of (−)-cytoxazone and its unnatural stereoisomer (+)-5-epi-cytoxazone from D-4-hydroxyphenylglycine in overall yields of 10% and 16%, respectively, is described. The stereoselective addition of cyanide to an N-Boc protected aminoaldehyde (tert-butyl ((R)-1-(4-methoxyphenyl)-2-oxoethyl)carbamate) (5) constitutes the key step in this approach, producing a mixture of cyanohydrins 6a and b (1,2-anti and 1,2-syn tert-butyl (2-cyano-2-hydroxy-1-(4-methoxyphenyl)ethyl)carbamate) in 89% yield, with reasonable stereoselectivity (1.0:1.8) in favor of the anti-Felkin product (1,2-syn). A one-pot sequence of three successive steps from this mixture produced the oxazolidinone isomers 9a and b ((4R,5R)- and (4R,5S)-4-(4-methoxyphenyl)-2-oxooxazolidine-5-carboxylate). Chromatographic column separation and reduction of the ester function of both precursors led to (−)-cytoxazone and (+)-5-epi-cytoxazone.
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