Efficient and versatile stereoselective synthesis of cryptophycins

Mast CA, Eissler S, Stoncius A, Stammler H-G, Neumann B, Sewald N. Efficient and versatile stereoselective synthesis of cryptophycins. Chemistry - A European Journal. 2005;11(16):4667-4677.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