Divergent synthesis of novel cylindrocyclophanes that inhibit methicillin-resistant Staphylococcus aureus (MRSA).

Divergent synthesis of novel cylindrocyclophanes that inhibit methicillin-resistant Staphylococcus aureus (MRSA). ChemMedChem. 2020 May 18;: Authors: Freudenreich J, Bartlett S, Kidd S, Forrest S, Spring D, Robertson N, Sore H, Galloway W, Welch M Abstract The cylindrocyclophanes are a family of macrocyclic natural products reported to exhibit antibacterial activity. Little is known about the structural basis of this activity due to challenges associated with their synthesis or isolation. We hypothesised that structural modification of the cylindrocyclophane scaffold could streamline their synthesis without significant loss of activity. Herein we report a divergent synthesis of the cylindrocyclophane core enabling access to symmetrical macrocycles by means of a catalytic, domino cross-metathesis-ring-closing metathesis cascade, followed by late-stage diversification. Phenotypic screening identified several novel inhibitors of methicillin-resistant S. aureus . The most potent inhibitor bears a unique tetrabrominated [7,7]paracyclophane core with no known counterpart in nature. Together these illustrate the potential of divergent synthesis using catalysis and unbiased screening methods in modern antibacterial discovery. PMID: 32424962 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research