Synthesis of a doubly labelled concanamycin derivative for ATPase binding studies

The synthesis of a doubly labelled concanamycin derivative for binding stud ies with V- and P-type ATPases is described. The starting point was 21-deox yconcanolide A (6), which was generated from concanamycin A (1) in three st eps and which exhibited the full ATPase inhibitor activity, with the advant age of a stability better than that of 1. Through use of a suitable protect ing group for 6, the carbene-generating diazirine residue and I-125 were in troduced regio- and stereo- selectively. The inhibitory efficacy of the res ulting 23-iodo(I-125)-9-O-[p-(trifluoroethyldiazirinyl)benzoyl]-21,23- dide oxyconcanolide A (11b) turned out to be high enough for labelling studies. Photoaffinity labelling experiments clearly showed that 11b is a suitable d erivative with which to determine the binding site of concanamycin-like com pounds in different ATPases.