A convenient procedure for the solid-phase synthesis of hydroxamic acids on PEGA resins

作者：Nandurkar Nitin S; Petersen Rico; Qvortrup Katrine; Komnatnyy Vitaly V; Taveras Kennedy M; Le Quement Sebastian T; Frauenlob Robin; Givskov Michael; Nielsen Thomas E^*

来源：Tetrahedron Letters, 2011, 52(52): 7121-7124.

DOI：10.1016/j.tetlet.2011.10.103

• Hydroxamic acids
• Solid-phase synthesis
• Hydroxylamine
• HDAC inhibitor
• PEGA resin

An efficient method for the solid-phase synthesis of hydroxamic acids is described. The method comprises the nucleophilic displacement of esters immobilized on PEGA resins with hydroxylamine/sodium hydroxide in isopropanol. The hydroxyaminolysis protocol is compatible with a broad range of PEGA-supported peptide and peptidomimetic esters. The methodology was found to be compatible with two new strategies for the synthesis of solid-supported lactams and diketopiperazines, respectively, both relying on the high inter- and intramolecular reactivity of cyclic N-acyliminium ions with electron-rich aromatics and heteroaromatics, ultimately affording hydroxamic acid derivatives in high purities.

• 出版日期2011-12-28