Figure 2. Synthesis of peptidocalix[4]arenes 3a,b and 6.

Reagents and conditions: (i) Boc-L-Arg(Pbf)-OH (N_α-Boc-N_ω-Pbf-L-arginine), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDAC), hydroxybenzotriazole (HOBt), N,N-dimethylaminopyridine (DMAP), dry CH₂Cl₂, rt, for 2a, or Boc-L-Lys(Boc)-OH, O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU), N,N-diisopropylethylamine (DIPEA), dry CH₂Cl₂, rt, for 2b; (ii, 1) TFA/triisopropylsilane (TIS)/H₂O (95/2.5/2.5), rt, for 3a, or TFA/triethylsilane (TES)/CH₂Cl₂ (10/2.5/87.5) at 0 °C for 3b, (2) dil. HCl in methanol, pH 4, rt; (iii) Cbz-L-Arg-OH, N,N′-dicyclohexylcarbodiimide (DCC), HOBt, dry DMF, rt, SAX (strong anion exchange) sorbent (Cl⁻); (iv) H₂/Pd(C), HCl, ethanol, rt. Boc: t-Butoxycarbonyl, Pbf: 2,2,4,6,7-pentamethyl-dihydrobenzofuran-5-sulfonyl, Cbz: carbobenzyloxy.