Selective alkylation/oxidation of N-substituted isoindolinone derivatives: Synthesis of N-phthaloylated natural and unnatural α-amino acid analogues

TETRAHEDRON LETTERS

卷:58

Article

Patil, Pravin C.¹  Luzzio, Frederick A.¹  Ronnebaum, Jarrid M.¹ 

[1] Univ Louisville, Dept Chem, 2320 South Brook St, Louisville, KY 40292 USA

关键词: Amino acids;    Isoindolinones;    Oxidation;    Protecting groups;    Non-proteinogenic;   

DOI  :  10.1016/j.tetlet.2017.08.032

来源: Elsevier

【 摘 要 】

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 alpha-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. (C) 2017 Elsevier Ltd. All rights reserved.

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