Ru‐Catalyzed C−H Hydroxylation of Tyrosine‐Containing Di‐ and Tripeptides toward the Assembly of L‐DOPA Derivatives
Paula Andrade‐Sampedro, Jon M. Matxain, Arkaitz Correa
Abstract
Abstract The development of catalytic tools for the late‐stage modification of amino acids within a peptide framework is a challenging task of capital importance. Herein, we report a Ru‐catalyzed C( sp 2 )−H hydroxylation of a collection of Tyr‐containing di‐ and tripeptides featuring the use of a carbamate as a removable directing group and PhI(OCOCF 3 ) 2 (PIFA) as oxidant. This air‐compatible tagging technique is reliable, scalable and provides access to L‐DOPA (L‐3,4‐dihydroxyphenylalanine) peptidomimetics in a racemization‐free fashion. Density Functional Theory calculations support a Ru(II)/Ru(IV) catalytic cycle. magnified image
Topics & Concepts
ChemistryTripeptideHydroxylationCatalysisPeptidomimeticRacemizationAmino acidCombinatorial chemistryRutheniumStereochemistryPeptideOrganic chemistryBiochemistryEnzymeCatalytic C–H Functionalization MethodsSynthesis and Catalytic ReactionsSulfur-Based Synthesis Techniques