Total Synthesis of Berkeleylactone A

The
first total synthesis of the potent antibiotic berkeleylactone
A is described in 10 steps with an overall yield of 9.5%. A key step
of our concise route is a late-stage, highly diastereoselective, sulfa-Michael
addition. The 16-membered macrocyclic lactone was formed via ring
closing metathesis and subsequent chemoselective reduction. The absolute
stereochemical configuration was confirmed by single-crystal X-ray
analysis. Synthetic berkeleylactone A was tested against several methicillin-resistant Staphylococcus aureus strains, and its potent antibacterial
activity was verified.