Synthesis of functionalized δ-hydroxy-β-keto esters and evaluation of their anti-inflammatory properties.

Grosse M, Günther K, Jordan PM, Roman D, Werz O, Beemelmanns C (2022) Synthesis of functionalized δ-hydroxy-β-keto esters and evaluation of their anti-inflammatory properties. Chembiochem 23(9), e202200073.

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 Mukaiyamaaldol reaction conditions. Diastereoselective reduction of δ,βdihydroxy esters afforded the respective syn- and anti-diols, and saponification yielded the respective acids. All products were evaluated for their anti-inflammatory properties, which uncovered a surprising structure-activity relationship.

Leibniz-HKI-Authors

Christine Beemelmanns
Michel Große
David Roman

Identifier

doi: 10.1002/cbic.202200073

PMID: 35244320