Total Synthesis Highlights

(enantiocontrol), using the proline-catalyzed procedure developed by MacMillan (Org. Chem.
Highlights 2004, January 26.). Protection and homologation of 6 then gave 1.
With most catalysts the dialdehyde 1 cyclized predominantly to the trans-fused product. With the
correct enantiomer of the organocatalyst, however, the cyclization could be directed toward the
desired cis-fused 2. Vilsmeier homologation of the electron-rich alkene followed by oxidation and
lactonization then delivered 8.
A glucose derivative such as 12 would usually be prepared over several protection and
deprotection steps from a commercially-available form of glucose. The authors took a different
approach, using the method for protected glucose synthesis they have developed (Org. Chem.
Highlights 2005, March 21.). Thus, proline-catalyzed dimerization of 9 gave 10, which after
condensation with 11 and benzylation gave 12.
Condensation of 12 with 8 gave the exo glycoside 13. Brief exposure of 13 to 350 nm irradiation
followed by debenzylation then gave 3. It is interesting to note that the photocyclization of 13
proceeded slowly even under ambient laboratory light, suggesting that this step in the biosynthesis
of 3 need not be enzyme-mediated.
64. Total Synthesis of (-)-Sordaricin