Synthesis of a Doubly Labelled Concanamycin Derivative for ATPase Binding Studies

The synthesis of a doubly labelled concanamycin derivative for binding studies with V- and P-type ATPases is described. The starting point was 21-deoxyconcanolide A (6), which was generated from concanamycin A (1) in three steps and which exhibited the full ATPase inhibitor activity, with the advantage of a stability better than that of 1. Through use of a suitable protecting group for 6, the carbene-generating diazirine residue and 125I were introduced regio- and stereoselectively. The inhibitory efficacy of the resulting 23-iodo(125I)-9-O-[p-(trifluoroethyldiazirinyl)benzoyl]-21,23-dideoxyconcanolide A (11b) turned out to be high enough for labelling studies. Photoaffinity labelling experiments clearly showed that 11b is a suitable derivative with which to determine the binding site of concanamycin-like compounds in different ATPases.