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

delta-Hydroxy-beta-keto esters and delta,beta-dihydroxy esters are characteristic structural motifs of statin-type natural products and drug candidates. Here, we describe the synthesis of functionalized delta-hydroxy-beta-keto esters in good yields and excellent enantioselectivities using Chan's diene and modified Mukaiyama-aldol reaction conditions. Diastereoselective reduction of delta,beta-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.

Automated summary

This study describes the synthesis of delta-hydroxy-beta-keto esters and their evaluation for anti-inflammatory properties. The products exhibited excellent enantioselectivities and surprising structure-activity relationship.