| A new method for the synthesis of macrocyclic lactones from activated carboxylates has been developed. We have shown that 2-alkyl-4,5-diphenyloxazoles may be cleanly converted to activated triamide species via the mild, neutral process of dye-sensitized photooxygenation. These activated carboxylates could then be cyclized under conditions of high dilution and acid catalysis to a series of simple macrocyclic lactones in 65-75% yields. The resultant leaving group, benzoyl benzamide, may then be separated chromatographically.; The stability and special mode of reactivity of the oxazole functionality has rendered it most amendable to synthetic application. In particular, the procedure described above has proven quite effective in the synthesis of polyether lactones, ((+OR-))-recifeiolide, a fungal metabolite of the species Cephalosporium recifei, ((+OR-))-di-O-methylcurvularin, a metabolite of the mold species curvularia and penicillium steckii, and (+)-antimycin A(,3), a novel antibiotic, antifungal dilactone macrolide isolated from a number of Streptomyces strains. |
