Enantioselective Synthesis of the Proposed Structure of Santinol D

In connection with structural verification of santinol D, a unique tricylglycerol isolated from Helichrysum italicum subsp. microphyllum, four possible isomers of its C-2'''and C-4''' centers were synthesized. The two enolizable chiral centers were installed with pre-defined absolute configurations using Evans alkylation and aldol condensation, respectively. The extra chiral center introduced in the aldol condensation was removed by Dess-Martin oxidation to convert the adjacent methine group into the highly enolizable subunit of an alpha-alkyl-beta-keto ester at the end of the synthesis. The synthetic isomers provided unequivocal physical and NMR data for every single enantiomer and thus provided the information required for the configurational assignment of this natural product. With the aid of a model compound, the racemization of such species was examined polarimetrically under several sets of typical conditions and the rates were also calculated from the corresponding kinetics data.