Total Synthesis of (+)-Papulacandin D.
A total synthesis of (+)-papulacandin D has been achieved in 31 steps, in a 9.2% overall yield from commercially available materials. The synthetic strategy divided the molecule into two nearly equal sized subunits, the spirocyclic C-arylglycopyranoside and the polyunsaturated fatty acid side chain. The C-arylglycopyranoside was prepared in 11 steps in a 30% overall yield from triacetoxyglucal. The fatty acid side chain was also prepared in 11 steps in a 30% overall yield from geraniol. The key strategic transformations in the synthesis are: (1) a palladium-catalyzed, organosilanolate-based cross-coupling reaction of a dimethylglucal-silanol with an electron rich and sterically hindered aromatic iodide and (2) a Lewis base-catalyzed, enantioselective allylation reaction of a dienal and allyltrichlorosilane. A critical element in the successful execution of the synthesis was the development of a suitable protecting group strategy that satisfied a number of stringent criteria.
Denmark
Scott E
SE
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801.
Kobayashi
Tetsuya
T
Regens
Christopher S
CS