Synthesis of 10 stereochemically distinct bis-tetrahydrofuran intermediates for creating a library of 64 asimicin stereoisomers

Stereoselective synthesis of 10 unique bifunctional stereoisomeric adjacent bis-THF intermediates (R = Bz), including 5.1–5.4, 5.7–5.9, 5.11, and 5.15–5.16, of 16 possible compounds, is described. The key steps used in the synthesis of these compounds included the rhenium(VII) oxide-mediated and the Co(modp)2-catalyzed trans oxidative cyclizations (OCs), the OsO4-catalyzed cis OC, and the Williamson’s type etherification reactions. The remaining six bis-THF intermediates (R = Bn) can be prepared from 5.7–5.9, 5.11, and 5.15–5.16 (R = Bz) in two steps, including protection of the free alcohol as benzyl ether followed by the benzoate deprotection. These intermediates should provide access to all 64 asimicin stereoisomers and their analogs.