A flexible and convenient approach was developed for the synthesis of 10-deoxymethynolide (
1) andnarbonolide (
2), which are aglycones of the methymycin and the pikromycin families of macrolideantibiotics. These lactones are produced by pikromycin polyketide synthase from
Streptomyces venezuelae.Polyketide lactones, 10-deoxymethynolide and narbonolide, which contain 12- and 14-membered rings,respectively, were synthesized efficiently. These target lactones were retrosynthetically divided into threeparts and assembled by using an asymmetric aldol reaction, the Yamaguchi esterification, and ring-closing metathesis. The ring-closing metathesis reaction catalyzed by the second-generation Grubbs catalystis particularly efficient in preparing these macrocyclic polyketide lactones.
