Scheme 2.

Synthesis of the EM-2 analogue Tyr-Pro Phe-Δ^ZPhe-NH₂ {[Δ^ZPhe⁴]EM-2} (2)^a

^a Reagents and conditions: (a) (CH₃CO)₂O/CH₃COONa, room temp, 24 h, (75%); (b) DMAP, MeOH, room temp, 12 h, (95%); (c) TFA/DCM (1:1), room temp, 1 h, (quantitative); (d) Boc-Pro-OH, EDC, HOBt, NMM, DCM, room temp, 12 h, (44%); (e) Boc-Tyr-OH, EDC, HOBt, NMM, DCM, room temp, 12 h, (40%); (f) NH₃/MeOH, room temp, 48 h, (55%).