Solution- and solid-phase syntheses of substituted guanidinocarboxylic acids

A library of guanidine-based compounds was produced to mimic the lead compo und 1, which is a substance known to have intensely sweet-taste characteris tics. Libraries of guanidinocarboxylic acids were therefore prepared via tw o synthetic methods. The solid-phase method involving trapping of solution- phase carbodiimides by supported amines was used to produce N,N'-dialkyl de rivatives (Scheme I). The second solid-phase method, featuring supported ca rbodiimides and solution-phase amines (Scheme 2), was devised to prepare N, N'-disubstituted and N,N',N'-trisubstituted guanidinocarboxylic acids. A sm all collection of guanadinoacetic acid dimers mid trimers was also prepared , but this time via a solution-phase coupling of carbodiimides to a polyami ne linker.