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

ABSTRACT: 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.

SUBMITTER: Peruzzi MT

PROVIDER: S-EPMC7328826 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Peruzzi Michael T MT Gallou Fabrice F Lee Stephen J SJ Gagné Michel R MR

Organic letters 20190417 9

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 inte ...[more]

PMID: 30993986

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