Total synthesis of (+)-frondosin A. Application of the Ru-catalyzed [5+2] cycloaddition.
The first total synthesis of (+)-frondosin A was accomplished in 19 longest linear and 21 total steps from commercially available materials. The key features of the synthesis include a Ru-catalyzed [5+2] cycloaddition, a Claisen rearrangement, and a ring expansion to construct the core of the frondosin A in a diastereoselective and regioselective fashion. This is the first application of a Ru-catalyzed [5+2] cycloaddition in the total synthesis of a natural product. Through this synthesis, the absolute configuration of (+)-frondosin A was established.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Hu
Yimin
Y
Horne
Daniel B
DB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D001688:Biological Products / Q000138:chemical synthesis*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D008956:Models, Chemical; D011161:Porifera / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
D000893:Anti-Inflammatory Agents; D001688:Biological Products; D001643:Bridged Bicyclo Compounds; C524890:frondosin A; D012428:Ruthenium