An RCM-Based Total Synthesis of the Antibiotic Disciformycin B.
Angew Chem Int Ed Engl. 2020 Jun 18;:
Authors: Altmann KH, Waser P
The total synthesis of the potent new antibiotic disciformycin B (2) is described, which shows significant activity against methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA/VRSA) strains. The synthetic route is based on macrocyclization of a tetraene substrate to the 12-membered macrolactone core by ring-closing olefin metathesis (RCM). Although macrocyclization was accompanied by concomitant cyclopentene formation by an alternative RCM pathway, conditions could eventually be established that gave the macrocycle as the major product. Key steps in the construction of the RCM-substrate included a highly efficient Evans syn-aldol reaction, the asymmetric Brown allylation of angelic aldehyde and the stereoselective Zn(BH4)2-mediated 1,2-reduction of an enone. The synthesis was completed by late-stage dehydrative glycosylation to introduce the D-arabinofuranosyl moiety and final chemoselective allylic alcohol oxidation.
PMID: 32558021 [PubMed - as supplied by publisher]