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Desymmetrization of pibrentasvir for efficient prodrug synthesis.

ABSTRACT: A novel and practical desymmetrization tactic is described to access a new class of pibrentasvir prodrugs. The homotopic benzimidazoles of pibrentasvir (PIB) are differentiated via a one-pot di-Boc/mono-de-Boc selective N-Boc protection and formaldehyde adduct formation sequence, both enabled by crystallization-induced selectivity. The first step represents the only known application of the Horeau principle of statistical amplification for C ₂-symmetric polyheterocycle regioselective functionalization. The resulting versatile intermediate is employed in the high-yielding preparation of several pibrentasvir prodrug candidates.

SUBMITTER: Voight EA

PROVIDER: S-EPMC8317637 | biostudies-literature |

REPOSITORIES: biostudies-literature

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