Synthesis And Optimization Of6α-Fluoroursodeoxycholic Acid

This article focuses on the synthesis and optimization of6α-fluoroursodeoxycholic acid. Starting from the commercially available chenodeoxycholic acid, after selective oxidation, esterification, fluorination and reduction ect in seven steps to get the target molecule in yield of70.4%.By the addition of NBS, the substrate can be selectively oxidized at C-7position in the mixture of acetone and H2O solution in high yield (95%).Using TMSCl/Nal to form the silyl enol ether5a in a mixture of toluene and acetonitrile at55℃. After aqueous workup, the crude solution was added to a suspension of Selectfluor, and6b was afforded with α/β=91/9,89/11and88/12at-40℃,-30℃and0℃respectively. However, when treating with NFSI analogues, the desilylated product6a was detected. Besides, the a-fluorinated product7b was obtained when reacted with PhCOCl in pyridine further.Reduction at C-7position by employing NaBH4/CeCl3was successfully proceeded, and8b was obtained with α/β=5/95which was further treated in the solution of NaOH/MeOH (1M) to afford6α-fluoroursodeoxycholic acid.