Site Selective Amide Reduction of Cyclosporine A Enables Diverse Derivation of an Important Cyclic Peptide.

Site selective amide reductions of the cyclic undecapeptide, cyclosporine A, have been developed using the combination of a heteroleptic borane catalyst and a silane reductant. Tertiary silane Me2EtSiH provides two unique cyclosporine A derivatives, one of which can be readily diversified in subsequent reactions. The secondary silane Et2SiH2 enables divergent reactivity that uses a free hydroxyl group to direct the reduction. The transient O-silyl hemiaminal intermediate of this reduction can additionally be trapped by reducing to the amine or by reductive cyanation.