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.
Madame Stéphanie Norsikian (Institut de Chimie des Substances Naturelles)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
UP-CiTCoM-8038 Cibles Thérapeutiques et Conception de Médicaments
ICSN Institut de Chimie des Substances Naturelles
Help of the ANR 433,287 euros
Beginning and duration of the scientific project: September 2021 - 48 Months