Synthesis of Functionalized δ-Hydroxy-ß-keto Esters and Evaluation of Their Anti-inflammatory Properties.

δ-Hydroxy-ß-keto esters and δ,ß-dihydroxy esters are characteristic structural motifs of statin-type natural products and drug candidates. Here, we describe the synthesis of functionalized δ-hydroxy-ß-keto esters in good yields and excellent enantioselectivities using Chan's diene and modified Mukaiyama-aldol reaction conditions. Diastereoselective reduction of δ,ß-dihydroxy esters afforded the respective syn- and anti-diols, and saponification yielded the corresponding acids. All products were evaluated for their anti-inflammatory properties, which uncovered a surprising structure-activity relationship.