A Convergent Enantioselective Route to Structurally Diverse 6-Deoxytetracycline Antibiotics

摘要: Complex antibiotics based on natural products are almost invariably prepared by semisynthesis, or chemical transformation of the isolated products. This approach greatly limits range accessible structures that might be studied as new antibiotic candidates. Here we report a short and enantioselective synthetic route to diverse 6-deoxytetracycline antibiotics. The common feature this class is scaffold four linearly fused rings, labeled A through D. We targeted not single compound but group with D ring site structural variability. late-stage, diastereoselective C-ring construction was used couple structurally varied D-ring precursors an AB precursor containing much essential functionality for binding bacterial ribosome. Five derivatives were synthesized from benzoic acid in yields ranging 5 7% over 14 15 steps, sixth, (-)-doxycycline, 8.3% yield 18 steps.