Unified Total Synthesis of Glycosylated Highly Strained Polyenic Macrolactam Antibiotics – SynTense

Focusing on innovation in strategy of synthesis, our goal is to design the first total synthesis of silvalactam, sipanmycins A and B, and incednine. These natural products have a very strained polyene macrolactam structure beta-glycosylated by an amino saccharide or diamino disaccharide. For a sustainable chemistry, we will favor catalysis, stereoselective reactions, redox-, step- and atom-economy and banish toxic elements. We will use innovative and DFT-guided strategies, and consider a unified strategy based on the chemistry of allene / alkyne couplings by dual catalysis, beta-selective glycosylations, three-component couplings and a robust approach to macrolactam closure. In addition, most of these molecules exhibit antibiotic activity (Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus and S. lentus) of interest in the context of the emergence of antibiotic resistance.