Solid phase synthesis of globomycin and SF-1902 A5

Abstract

The syntheses of the natural lipocyclodepsipeptide-type antibiotics globomycin and SF-1902 A5 are reported utilizing solid phase technology for the construction of the peptidic fragment and a new asymmetric methodology of epoxidation for the preparation of the lipidic chain. The linkage between both fragments was successfully achieved in solid phase to complete the syntheses via a macrolactonization reaction executed prior to the cleavage of the acyclic precursors from the solid support. These syntheses provide access to the rapid generation of a library of analogues via modification of the aminoacid residues as well as the lipidic chain, thus facilitating the identification of new antibiotics with interesting mechanisms of action based upon the inhibition of the enzyme signal peptidase II.