L-Tyrosine → HCID 87647670, compound

Participants

Reaction Steps

Ester bond between the pipecolic handle and side chain of amino acids was formed by using BOP/DIEA coupling for 90 minutes. Loading was determined by Fmoc titration on aliquots of resins 12, 14 and 18 for Thr, Ser and Tyr-functionalized resins, respectively (Table 3). Surprisingly, use of DIC/DMAP activation didn't give better result than BOP/DIEA mediated esterification. In a general manner, alcohol immobilization was less efficient than amine loading, according to Fmoc titration results, even when a negative malachite green test was observed. In particular with resins 12 and 14, obtained by the esterification of Fmoc-Thr-OMe and Fmoc-Ser-OMe side chains, experimental loadings were only 0.30 mmol/g and 0.32 mmol/g (i.e. 43% and 44% yield compared to maximum theoretical loading of 0.70 mmol/g). This result has to be put in perspective with the difficulty of loading primary alcohols on trityl-based resins giving experimental loading yields lower than 20% when compared to theoretical maximum loading (Barlos et al., 1988).

Provenance & Evidence