title: Chemoselective Wittig and Michael ligations of unprotected peptidyl phosphoranes in water furnish potent inhibitors of caspase-3.
abstract: Unprotected peptidyl phosphoranes 1 with sequence Ac-L-aspartyl-L-glutamyl-L-valinyl-L-aspartyl are released from polymer support and react with aliphatic and aromatic aldehydes in aqueous medium in a Wittig ligation. Obtained vinyl ketones 6-12 are potent inhibitors of caspase-3. Vinyl ketone 6, derived from formaldehyde, undergoes Michael ligations with thiol nucleophiles furnishing products 14-16, also in aqueous medium. The demonstrated ligation reactions enable the modification of complex functionalized peptides in water providing bioactive protein ligands without side-chain protection.
authors.affiliation: Medicinal Chemistry, Free University Berlin , Königin-Luise-Strasse 2 + 4, 14195 Berlin, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Holland-Nell
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Fernández-Bachiller
authors.lastname: Ahsanullah
authors.forename: Jörg
authors.initials: J
authors.lastname: Rademann
mesh_terms: D053148:Caspase 3 / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010753:Phosphoranes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D061945:Caspase Inhibitors; D009842:Oligopeptides; D010753:Phosphoranes; D014867:Water; D053148:Caspase 3