A Chemoenzymatic Total Synthesis of the Undecenolide (–)-Cladospolide C

The (-)-enantiomer, ent-3, of the natural product (+)- cladospolide C (3) has been prepared for the first time using the monochiral cis-1,2-dihydrocatechol 5 as starting material. Key steps include coupling of the derived acid 6 with the enzymatically generated (S)-(+)-4-penten-2-ol ( 7) and ring-closing metathesis (RCM) of the resultant doubly unsaturated ester 8 to give lactone 9. The structure of this last compound has been confirmed by single-crystal X-ray analysis. This work has established that the absolute configuration of (+)- cladospolide C has been correctly assigned and is as illustrated in structure 3.