Highly Selective Directed Iridium-Catalyzed Hydrogen Isotope Exchange Reactions of Aliphatic Amides.

ABSTRACT: For the first time, we describe highly selective homogeneous iridium-catalyzed hydrogen isotope exchange (HIE) of unactivated C(sp3 ) centers in aliphatic amides. When using the commercially available Kerr catalyst, the HIE with a series of common antibody-drug conjugate (ADC) linker side chains proceeds with high yields, high regioselectivity, and with deuterium incorporation up to 99?%. The method is fully translatable to the specific requirements of tritium chemistry and its effectiveness was demonstrated by direct tritium labelling of a maytansinoid. The scope of the method can be extended to simple amino acids, with high HIE activity observed for glycine and alanine. In di- and tripeptides, a very interesting protecting-group-dependent tunable selectivity was observed. DFT calculations gave insight into the energies of the transition states, thereby explaining the observed selectivity and the influence of the amino acid protecting groups.

SUBMITTER: Valero M 

PROVIDER: S-EPMC6033151 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature