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. 2017 Sep 6;23(58):14410–14415. doi: 10.1002/chem.201703093

Scheme 1.

Scheme 1

Synthesis of (cyclo[DKP‐RGD])n‐Val‐Ala‐PTX (n=1, 2, 3, or 4) conjugates 5 – 9. Reagents and conditions: a) 1) piperidine (5 equiv), DMF, RT, 2 h; 2) acids 10 – 14 (1.5 equiv), HATU (1.7 equiv), HOAt (1.7 equiv), iPr2NEt (4 equiv), DMF, RT, overnight (16  a – 16  e); b) 1) 1:2 TFA/CH2Cl2, 45 min; 2) 17 (1.5 equiv), iPr2NEt (4 equiv), DMF, RT, overnight; c) 19 (1 equiv) 18  a or 18  b (1.5 equiv), CuSO4 ⋅5 H2O (0.5 equiv), sodium ascorbate (0.6 equiv), 1:1 DMF/H2O, 30 °C, overnight; d) 18  c (1 equiv), 19 (3 equiv) CuSO4 ⋅5 H2O (1 equiv), sodium ascorbate (1.2 equiv), 1:1 DMF/H2O, 30 °C, overnight; e) 18  d (1 equiv), 19 (3.6 equiv) CuSO4 ⋅5 H2O (1.5 equiv), sodium ascorbate (1.8 equiv), 1:1 DMF/H2O, 30 °C, overnight; f) 18 e (1 equiv), 19 (4.8 equiv) CuSO4 ⋅5 H2O (2 equiv), sodium ascorbate (2.4 equiv), 1:1 DMF/H2O, 30 °C, overnight.