Synthetic studies on ezomycins: stereoselective route to a thymine octosyl nucleoside derivative

The ezomycins are Streptomyces-derived antifungal natural products, belonging to the complex peptidyl nucleoside family of antibiotics. Employing D-serine as a chiral platform, we report herein a novel synthetic route to the bicyclic octosyl nucleoside core of the ezomycins. A key step in the sequence involved a stereoselective 6-exo-trig oxymercurationoxidation of a strategic delta-hydroxy alkene derivative, toward construction of the trans-fused furopyran ring system as present in the target products. In contrast to the known carbohydrate-based synthetic routes to the above furopyranyl fragment, the present amino acid chiral template approach is expected to offer a more flexible pathway toward potential SAR-targeted structural/stereochemical modifications of this central bicyclic nucleoside component of the ezomycins.