Solid-Phase Guanidinylation of Peptidyl Amines Compatible with Standard Fmoc-Chemistry: Formation of Monosubstituted Guanidines
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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 and bioactive analogs. Among many approaches, peptide/peptidomimetic
guanidinylation offers access to analogs possessing functionality with strong basic properties, capable of forming stable
intermolecular H-bonds, charge pairing, and cation-π interactions. Therefore, guanidinium functional group is considered as
an important pharmacophoric element. Although a number of methods for solid-phase guanidinylation reactions exist, only a
few are fully compatible with standard Fmoc solid-phase peptide chemistry.
In this chapter we summarize the solid-phase guanidinylation methods fully compatible with standard Fmoc-synthetic methodology.
This includes use of direct guanidinylating reagents such as 1-H
-pyrazole-1-carboxamidine and triflylguanidine, and guanidinylation with di-protected thiourea derivatives in combination
with promoters such as Mukaiyama’s reagent, N
-iodosuccinimide, and N
,N′
-diisopropylcarbodiimide.
