Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part II: Folic acid conjugates of tubulysins and their hydrazides

Efficient syntheses of folate conjugates of tubulysins and their hydrazides 1a-d are described. These water soluble folate receptor (FR) targeted conjugates are derivatives of folic acid and the potent cyto toxic agents: tubulysin A, B, or their respective hydrazides, connected in regioselective manner via a hydrophilic peptide spacer and a reducible disuffide linker. (c) 2008 Elsevier Ltd. All rights reserved.