Novel amidine conjugates of the ornithine moiety of the macrocyclic antifungal lipopeptidolactone FR901469.

moiety of 1.8) We have also reported novel methodology for the synthesis of the amide analog of 19) and non-ornithinecontaining macrocyclic lactones.10) Herein, we describe the synthesis and evaluation of a newseries of amidine analogs of the ornithine moiety of FR901469, and the discovery of pyrazolium derivative 8 with reduced hemolytic activity and comparable efficacy to 1 in a murine model of disseminated candidiasis. Amidine derivatives were prepared as shown in Scheme 1. Coupling of FR901469 with imidate esters (obtained