THE CHEMISTRY OF UNUSUAL MACROLIDES .2. SPECTROSCOPIC AND BIOSYNTHETIC INVESTIGATIONS OF THE V-TYPE ATPASE INHIBITOR CONCANAMYCIN-A

H-1- and C-13-NMR spectre of the conformationally flexible macrolide c oncanamycin A (1) have been assigned by the use of 2D NMR techniques a t low temperatures and have enabled biosynthetic studies on this most potent inhibitor of vacuolar ATPases. By feeding of different [C-13]-l abeled precursors to Streptomyces sp. (strain Go 22/15) the polyketide origin of the concanamycin skeleton was proved. It arises from a tetr adecaketide, which is based on four acetate and seven propionate units besides one butyrate and two unusual C-2 building blocks from the tri ose pool. In combination with former findings it is possible to predic t the biogenetic assembly of several strongly related unusual macrolid es, for which the group name ''plecomacrolides'' should be used in fut ure. The results are discussed in the light of modern hypothesis as st ated for polyketide pathways.