Efficient synthetic access to a new family of highly potent bryostatin analogues via a Prins-driven macrocyclization strategy.
The step-economical synthesis of a new class of bryostatin analogues that contain the complete oxycarbocyclic core ring system of the bryostatin natural products is reported. These agents are convergently assembled via a highly efficient, functional-group-tolerant, and stereoselective Prins-driven macrocyclization. These tetrahydropyranyl B-ring analogues are among our most potent and efficacious analogues to date, exhibiting nanomolar and picomolar activities in protein kinase C affinity assays as well as in cellular antiproliferation assays.
Wender
Paul A
PA
Departments of Chemistry and Chemical and Systems Biology, Stanford University, Stanford, California 94305-5080, USA. wenderp@stanford.edu
Dechristopher
Brian A
BA
Schrier
Adam J
AJ
D054713:Bryostatins / Q000138:chemical synthesis*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis*; D011493:Protein Kinase C / Q000737:chemistry
D054713:Bryostatins; D047028:Macrocyclic Compounds; D011493:Protein Kinase C