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

SUBMITTER: Valero M 

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

REPOSITORIES: biostudies-literature