A synthesis of (+)-FR182877, featuring tandem transannular Diels-Alder reactions inspired by a postulated biogenesis.
An efficient biomimetic synthesis of the reported structure of the hexacyclic, cytotoxic secondary metabolite FR182877 is described. The successful route features the synthesis of a 19-membered ring carbocycle using two pi-allyl palladium(II)-mediated C-C bond-forming reactions. This polyunsaturated macrocycle undergoes tandem transannular Diels-Alder reactions that create five rings and seven stereogenic centers in one operation under mild conditions, representing the first double transannular Diels-Alder reaction. The absolute stereochemistry of the natural product is demonstrated to be opposite of that reported previously. Significant quantities of both enantiomers of this microtubule-stabilizing natural product and related structures are now available via this approach.
Vosburg
David A
DA
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Vanderwal
Christopher D
CD
Sorensen
Erik J
EJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D011083:Polycyclic Compounds / Q000138:chemical synthesis*
D000970:Antineoplastic Agents; C408303:FR 182877; D011083:Polycyclic Compounds