Scheme 1.

Synthetic pathway to benzoxazole analogue 2 of HeE1-2Tyr (1). Reagents and conditions: a) TMSN₃, TfOH, DCM, rt, overnight, b) BnBr, NaH, DMF, 0 °C to rt, 1 h, c) (R = Et) diethyl carbonate, LiHMDS, THF, −78 to 0 °C, 1 h, d) (R = allyl) allyl chloroformate, LiHMDS, THF, −78 to 0 °C, 1 h, e) POCl₃, DMF, 90 °C, 30 min, f) (BnCO)₂O, 100 °C, 1.5 h, g) methanesulfonic acid, DCM, 0 °C to rt, 4 h, h) CyOH, PPh₃, DIAD, 1,4-dioxane, 50 °C, overnight, i) (R = Et) NaOH, H₂O, EtOH, 75 °C, 3 h, j) (R = allyl) Et₃SiH, PPh₃, Pd(OAc)₂, ACN, rt, k) H–ʟ-Tyr–OMe, HOBt, EDCI, TEA, DCM, DMF, rt, 12 h, l) LiOH⋅H₂O, H₂O, 1,4-dioxane, rt, 45 min. Cy = cyclohexyl.