Spermidine as a potential biosynthetic precursor to the 1,5-diazabicyclo[4: 3 : 0]nonene residue in the efrapeptins

Efrapeptins are a group of microheterogeneous polypeptide antibiotics produ ced by the fungus Tolypocladium niveum, which are potent inhibitors of mito chondrial F-1-ATPase. Efrapeptins contain an unusual 1,5-diazabicyclo[4:3:0 ]nonene (DBN) residue at the C-terminus, This study, is driven by the hypot hesis that the DBN residue could, in principle, arise by oxidative cyclizat ion of a spermidine moiety. Electrospray ionization mass spectrometry of th e peptide antibiotics 'elvapeptins' from T. niveum, establishes the presenc e of a C-terminal spermidinie residue. Conversion of elvapeptins to efrapep tins by CuCl/pyridine demonstrates the transformation of the spermidine res idue to the 1,5-diazabicyclo[4:3:0]nonene system by oxidative cyclization.