Chemical synthesis of chenodeoxycholic acid

News

Yourlocation： Home > News > Chemical synthesis of chenodeoxycholic acid

Initially most of the high purity chenodeoxycholic acid was produced from a wide range of sources of cholic acid. In the synthesis of chenodeoxycholic acid, the most common method is to reduce the 12-position carbonyl method, the process of the key intermediate product for the compound (5). 1933 Kawai and so the first use of cholic acid synthesis of chenodeoxycholic acid. Through the partial hydrogenation of dehydrocholic acid, and then in ethanol and semicarbazide, sodium ethoxide reaction, to further reduction, obtained chenodeoxycholic acid.
Plattner and Heusser were acetylated by the Borsche method followed by oxidation with chromium trioxide in glacial acetic acid to produce 12-carbonyl compounds which were converted to the corresponding methyl ester by reaction with diazomethane in dioxane (5), and then reduced by Wolff-Kishner method to obtain chenodeoxycholic acid (1). Huang-Minlon improved the Wolff-Kishner reduction method, replacing ethanol and sodium ethoxide with potassium hydroxide or sodium hydroxide in triethylene glycol or diethylene glycol, and because the water was removed in the initial step. Excess hydrazine hydrate can inhibit the production of isomers, and most of the ketoacids can be successfully reduced by the Huang-Minlon modified method.
Synthesis of chenodeoxycholic acid with methyl bile acid. In the presence of hydrogen chloride gas, the cholic acid is esterified with methanol to give methyl choline (3) and the C3 and C7 hydroxyl groups are acetylated, followed by oxidation with potassium chromate (5), and finally the Huang-Minlon method Get chenodeoxycholic acid. Anderson et al. Removed 3α, 7α-diacetyl-12-keto-5β-cholic acid, purified methyl ester and then reduced to obtain chenodeoxycholic acid. Sato and Ikekawa 3α, 7α-diacetyl-12-keto-
5β-cholic acid methyl ester (5) was converted to the corresponding thioketone derivative, and the group on C12 was removed by Raney-nickel desulfurization. The yield was as high as 90% by hydrolysis. However, the drawback of this method is that the thiophene derivative is difficult to remove from the produced chenodeoxycholic acid with 3α, 7α-diacetyl-12-keto-5β-cholic acid.
Lida and Chang with chitosan as raw material, toluenesulfonyl hydrazone (6) as the key intermediate synthesis of chenodeoxycholic acid. 3α, 7α-diacetyl-12α-hydroxy-5β-cholic acid methyl ester is oxidized to the carbonyl derivative (5) by Fieser and reacted with p-toluenesulfonyl hydrazide at room temperature for 12 hours (6). Followed by reduction of toluenesulfonyl hydrazide with NaBH4 in glacial acetic acid to give chenodeoxycholic acid in a yield of 38%. Japanese scholar Takahaski improved the process of acetylation of cholic acid, with propionic acid, butyric acid and other homologues instead of acetic acid for acylation, the yield has been significantly improved.