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

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.

SUBMITTER: Grosse M

PROVIDER: S-EPMC9314795 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Grosse Michel M Günther Kerstin K Jordan Paul M PM Roman Dávid D Werz Oliver O Beemelmanns Christine C

Chembiochem : a European journal of chemical biology 20220319 9

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 ...[more]

PMID: 35244320

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