Scheme 3. Synthesis of C16-aminoratjadones bearing short terminal alkyne moieties and enzymatically cleavable Val-Cit-pABA or disulphide linkers. Reagents and conditions: (a) 22 (1.1 equiv.), NMM (3.0 equiv.), (CH2C12). 23 °C, 1.5 h, 65% for 20; (b) 24 (1.1 equiv.), NMM (3.0 equiv.), (CH2C12), 23 °C, 20 h; 90% for 21 and 69% for 22; (c) 27 or 28 (1.1 equiv.), NMM (6.0 equiv.), (DMF), 23 °C. 26 h, 76% for 25 and 66% for 26; (d) 30 (1.0 equiv.), TSTU (1.0 equiv.), NMM (5.0 equiv.), (DMF), 23 °C, 15 h, 65% for 29; (e) 32 (1.0 equiv.), (MeCN : PBS (pH = 7.45)/1 : 2), 0 °C to 23 °C, 2.5 h, 70% for 31.
