Author/Authors :
Nandurkar، نويسنده , , Nitin S. and Petersen، نويسنده , , Rico and Qvortrup، نويسنده , , Katrine and Komnatnyy، نويسنده , , Vitaly V. and Taveras، نويسنده , , Kennedy M. and Le Quement، نويسنده , , Sebastian T. and Frauenlob، نويسنده , , Robin and Givskov، نويسنده , , Michael and Nielsen، نويسنده , , Thomas E.، نويسنده ,
Abstract :
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.
Keywords :
Hydroxamic acids , solid-phase synthesis , HDAC inhibitor , PEGA resin , hydroxylamine
