848890-33-5

Upstream product

• 3249-68-1 ethyl butyroyl acetate 
• 67271-32-3 ethyl 2-chloro-3-oxohexanoate 
• 823214-61-5 ethyl 2-(4-chlorophenoxy)-3-oxohexanoate 

Relevant academic research and scientific papers

Synthesis and biological evaluation of new clofibrate analogues as potential PPARα agonists

Clofibrate is a lipid-profile modifying agent belonging to the fibrate class of drugs. Fibrates are known to exhibit their beneficial effects by activating peroxisome proliferator-activated receptor-α (PPARα) and used in the treatment of dyslipidemia and atherosclerosis and for the prevention of heart failure. Hereby, the preparation of two new sets of clofibrate analogues, ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates and ethyl 2-(4-chlorophenoxy)-3-hydroxyalkanoates is described starting from commercially available 3-oxoalkanoates in fair to good yields. Treatment of 3-oxoalkanoates with SO2Cl2 yielded the corresponding 2-chloro-3- oxoalkanoates, that were then converted into 2-(4-chlorophenoxy)-3-oxoalkanoates by reacting with sodium or caesium 4-chlorophenate. Reduction of the keto group with NaBH4 afforded the corresponding 2-(4-chlorophenoxy)-3- hydroxyalkanoates in very high yields and with variable diastereoselectivity. Biological evaluation of the compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. The newly synthesised clofibrate analogues failed to show noticeable levels of PPAR activation at concentrations where clofibrate showed an evident activity, suggesting that the structural modifications caused the loss of PPAR activity.

Screening yeasts for the stereoselective reduction of oxoester clofibrate analogues

Reduction of oxoesters 1b-d and 1f,g in the presence of different yeast strains (Saccharomyces cerevisiae DSM 11285, S. cerevisiae CBS 7336, Cryptococcus curvatus ATCC 20509, Candida bombicola ATCC 22214, Trigonopsis variabilis DSM 70714, Kluyveromyces ma