The Chemistry of Unusual Macrolides, 3. δ‐Lactone Glycosides by C‐C Bond Cleavage of Concanamycin C and Elaiophylin Hydroperoxides

A cleavage method by which the prelactones of the plecomacrolides concanamycin C ( 2 ) and elaiophylin ( 8 ) can be obtained was developed. A hydroperoxide in the position of the hemiketal hydroxy group of 2 and 8 was generated selectively by treatment with H 2 O 2 /VO(acac 2 ) or H 2 O 2 /WO 3 . Application of Fe 2+ salts (Fenton reaction) to 3 and 9 led to the prelactone glycosides 11 and 15 , the structures of which were established by spectroscopic analysis and comparison with the natural prelactone 10 and semisynthetic lactone 12 , which both were obtained by a similar reaction sequence from the concanolide derivatives 4 and 6 . The highly functionalized chiral δ‐lactone glycosides 11 and 15 , which cannot be obtained by genetic engineering of the polyketide synthase of the parent plecomacrolides, represent the right‐hand side of the remarkably active ATPase inhibitor and will be of interest concerning structure‐activity relationships.