Scheme 8.

Synthesis of 13¹,15²-di(amino acid) derivative 33. (Reagents: i. 1.5 equiv NH₂CH₂CH₂CO₂t-Bu, toluene, 100 °C, 12-16 h, 54%; ii. TFA, CH₂Cl₂ 1:3, 6 h, rt, 99%; iii. L-Asp di-t-Bu.HCl, DIEA, CH₂Cl₂, HOBt, TBTU, DMF, 59%; iv. 10 equiv NH₂CH₂CH₂NH₂, toluene, 45 °C, 12 h, 58%; v. Boc-Lys(Boc)-OH, DCHA, DIEA, CH₂Cl₂, HOBt, TBTU, DMF; vi. TFA, CH₂Cl₂ 1:3, 6 h, rt, 88%; iv. Boc-Asp(O-t-Bu)OH, DIEA, CH₂Cl₂, TBTU, DMF, 40%; iv. TFA/CH₂Cl₂ 1:3, 12 h, rt, 48% (2 steps).