Solid-phase guanidinylation of peptidyl amines compatible with standard Fmoc-chemistry: formation of monosubstituted guanidines.

摘要: With the growing importance of peptides and peptidomimetics as potential therapeutic agents, a continuous synthetic interest has been shown for their modification to provide more stable bioactive analogs. Among many approaches, peptide/peptidomimetic guanidinylation offers access analogs possessing functionality with strong basic properties, capable forming intermolecular H-bonds, charge pairing, cation-π interactions. Therefore, guanidinium functional group is considered an important pharmacophoric element. Although number methods solid-phase reactions exist, only few are fully compatible standard Fmoc peptide chemistry.In this chapter we summarize Fmoc-synthetic methodology. This includes use direct guanidinylating reagents such 1-H-pyrazole-1-carboxamidine triflylguanidine, di-protected thiourea derivatives in combination promoters Mukaiyama's reagent, N-iodosuccinimide, N,N'-diisopropylcarbodiimide.