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Synthesis of Functionalized δ-Hydroxy-β-keto Esters and Evaluation of Their Anti-inflammatory Properties
Michel Grosse1, Kerstin Günther2, Paul M Jordan2
1Chemical Biology of Microbe-Host Interactions, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute (HKI), Beutenbergstrasse 11a, 07745, Jena, Germany.
Abstract:
δ-Hydroxy-β-keto esters and δ,β-dihydroxy esters are characteristic structural motifs of statin-type natural products and drug candidates. Here, we describe the synthesis of functionalized δ-hydroxy-β-keto esters in good yields and excellent enantioselectivities using Chan's diene and modified Mukaiyama-aldol reaction conditions. Diastereoselective reduction of δ,β-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.
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