Efficient and Versatile Stereoselective Synthesis of Cryptophycins

The cryptophycins are a family of cyclic depsipeptides with four retrosynthetic units A to D which correspond to the respective amino acids and hydroxy acids. A new synthetic route to unit A allows the selective generation of all four stereogenic centres by introducing two of them in a catalytic asymmetric dihydroxylation, followed by substrate‐controlled diastereoselective reactions. The diol also serves as the epoxide precursor. This approach provides selective access to stereoisomers of unit A (enantiomers, epimers) for structure–activity relationship studies. The unit A derivatives were incorporated into cryptophycin‐1, cryptophycin‐52 and a novel epimer of cryptophycin‐52.