Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 4745-4759 |
Number of pages | 15 |
Journal | Tetrahedron |
Volume | 66 |
Issue number | 26 |
DOIs | |
State | Published - Jun 26 2010 |
Keywords
- Asymmetric allylation
- C-Arylglycosides
- Silicon-based cross-coupling
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry