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Synthesis of Fmoc-Ddae-OH linker. (A) Reaction conditions previously reported in the literature. (b) Reaction conditions using DCC produced the highest yield, however N, N’ dicyclohexylurea byproduct formation made purification difficult. (c) Reaction conditions with little byproduct formation and high yield consisted of N-Fmoc-amido dPEG-acid, 1.1 eq. dimedone, 1.1 eq. EDC-HCl, 1.1 eq. DIEA and 0.1 eq. DMAP in DCM.
