Selective alkylation/oxidation of N-substituted isoindolinone derivatives: Synthesis of N-phthaloylated natural and unnatural α-amino acid analogues |
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Authors: | Pravin C Patil Frederick A Luzzio Jarrid M Ronnebaum |
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Institution: | Department of Chemistry, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA |
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Abstract: | The interchangeability of the isoindolinone group as a nitrogen protecting group for amino acid intermediates is demonstrated by the preparation of several natural and unnatural α-amino acid derivatives using a two-carbon N-isoindolinone (phthalimidine) scaffold. Using a selective benzylic oxidation, the N-isoindolinone group is then converted to the N-phthaloyl group for convenient removal (65–98%). For preparation of the isoindolinone products which were to be the substrates for benzylic oxidation, a range of side chains were installed on the isoindolinone-protected glycine equivalent on deprotonation to demonstrate the utility of the N-protected isoindolinone synthon (51–93%). While the ensuing benzylic oxidation is employed successfully for converting the N-isoindolinone group to the N-phthaloyl group in simple substrates, substrates bearing unsaturated or electron-rich side chains respond poorly to the oxidation. |
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Keywords: | Amino acids Isoindolinones Oxidation Protecting groups Non-proteinogenic |
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