A Nine-Step Total Synthesis of (-)-Platencin

[GRAPHICS] Within 1 year, platencin, A recently discovered antibiotic, has become a highly competitive synthetic target, due to its promising bioactivity and its unusual complex molecular architecture. Herein, a particularly concise total synthesis of platencin starting from inexpensive perillaldehyde is described. The key features of this approach are (1) a highly diastereoselective Diels-Alder reaction with Rawal's diene-forming the first all-carbon quaternary center, (2) a ring-closing metathesis to generate the strained tricylic skeleton, (3) a hydration/dehydration strategy to efficiently shift the endocyclic alkene to the exoposition, and (4) a 1,4-addition of a hindered ketone enolate to methyl acrylate to create the second all-carbon quaternary center. In view of the brevity (nine linear steps) and the overall yield of 10%, our synthesis compares favorably with all the previous ones.