Cyclizing Pentapeptides: Mechanism and Application of Dehydrophenylalanine as a Traceless Turn-Inducer
journal contributionposted on 15.12.2016, 09:53 by Diane N. Le, Jan Riedel, Natalia Kozlyuk, Rachel W. Martin, Vy M. Dong
Dehydrophenylalanine is used as a traceless turn-inducer in the total synthesis of dichotomin E. Macrocyclization of the monomer is achieved in high yields and selectivity over cyclodimerization under conditions 100 times more concentrated than previously achieved. The enamide facilitates ring closing, and Rh-catalyzed hydrogenation of the unsaturated cyclic peptide results in selective formation of the natural product or its epimer, depending on our choice of phosphine ligand. NMR analysis and molecular modeling revealed that the linear peptide adopts a left-handed α-turn that preorganizes the N- and C-termini toward macrocyclization.
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phosphine ligandMechanismselectivityApplicationenamideC-terminipreorganizetraceless turn-inducermacrocyclizationmonomerNMR analysisCyclizing Pentapeptidesconditions 100 timesRh-catalyzed hydrogenationTraceless Turn-Inducer DehydrophenylalanineMacrocyclizationsynthesiscyclic peptide resultschoiceformationepimermodelingα-cyclodimerizationyielddichotomin E