Transition metal-free selective C-S bond cleavage of Ugi-adducts for rapid preparation of peptidomimetics

A transition metal-free C-S bond cleavage and subsequent Mannich reaction of Ugi-adducts with alcohols as well as thiols is developed. Diverse novel peptidomimetics containing N,O- or N,S-aminals are synthesized in a rapid, highly efficient and step-economical fashion. This method features exclusive selectivity, broad substrate scope, excellent yield and functional group tolerance, and was applied on substrates derived from the pharmaceuticals febuxostat, probenecid and memantine.

Automated summary

A transition metal-free method for C-S bond cleavage and Mannich reaction of Ugi-adducts with alcohols and thiols has been developed, leading to the synthesis of diverse novel peptidomimetics containing N,O- or N,S-aminals. This method exhibits exclusive selectivity, broad substrate scope, excellent yield, and tolerance towards different functional groups, and has been successfully applied to substrates derived from pharmaceuticals febuxostat, probenecid, and memantine.