Synthesis of macrocyclic scaffolds suitable for diversity-oriented synthesis of macrolides

Synthesis of macrocyclic glycal-based scaffolds for diversity-oriented synthesis was studied and demonstrated using macrocyclic enyne ring-closing metathesis. The roles of ring size, alkyne substitution, and orientation relative to the glycal were studied. In all cases, the cyclization showed preference for the thermodynamically favored endo-mode of closure and a trans-double bond at the ring-closure site, leaving macrocyclic scaffolds all containing multiple orthogonal functional groups available for further diversification.