Proline editing general approach: automated synthesis of the peptide Ac-TYHypN-NH2(1) via trityl hydroxyl protection.a
a (a) 20% piperidine/DMF; (b) Fmoc-Asn(Trt)-OH, HBTU, DIPEA/DMF; (c) Fmoc-Tyr(OtBu)-OH, HBTU, DIPEA/DMF; (d) Fmoc-Thr(OtBu)-OH, HBTU, DIPEA/DMF; (e) 10% Ac2O/pyridine. RN′ = Ac-Thr(OtBu)-Tyr(OtBu)-, RC′ = -Asn(Trt)-NHRink-Resin. RN = Ac-Thr-Tyr-, RC = -Asn-NH2. For all peptides in all schemes, the prime designation (e.g. 1′, RN′, RC′) indicates the protected peptide on solid phase, whereas the absence of a prime designation indicates free peptide in solution.