The constrained tryptophan (Trp) analog 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (Tcc) is used to restrict peptide conformation in structure–activity relationship studies. Although Pictet–Spengler cyclization of Trp and aldehydes with mineral acid gives Tcc analogs, such harsh conditions do not tolerate acid-labile functionality. To enable broader use of Tcc residues, mild conditions are now reported for the on-resin Pictet–Spengler cyclisation in the presence of acid-labile side chain protection and linker strategies.
ABSTRACT
The constrained tryptophan (Trp) analog 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (Tcc) is used to restrict peptide conformation in structure–activity relationship studies. Although Pictet–Spengler cyclization of Trp and aldehydes with mineral acid gives Tcc analogs, such harsh conditions do not tolerate acid-labile functionality. To enable broader use of Tcc residues, mild conditions are now reported for the on-resin Pictet–Spengler cyclisation in the presence of acid-labile side chain protection and linker strategies.
