Scheme 2. Synthesis of oxetane modified pentapeptide 1. Reagents and conditions: (a) TFA/CH2Cl2 (1 : 1), 1 h; (b) (i) oxetan-3-one (2.0 equiv.), MeNO2 (2.8 equiv.), Et3N (0.4 equiv.), 0 °C to RT, 1 h; (ii) MeSO2Cl (2.0 equiv.), Et3N (4.0 equiv.), CH2Cl2, –78 °C, 1.5 h; (iii) amine from (a), Et3N (1.5 equiv.), –78 °C to RT, 16 h; (c) RANEY® Ni, H2, Boc-Ala-OSu (1.5 equiv.), THF, 4 h; (d) TFA/CH2Cl2 (1 : 1), 1 h; (e) Cbz-Leu-OH (1.1 equiv.), EDC·HCl (1.1 equiv.), HOBt·H2O (1.1 equiv.), NMM (4.0 equiv.), CH2Cl2, 24 h; (f) 10% Pd/C, H2, MeOH, 16 h.
