Synthesis of homoursodeoxycholic acid and 3H>homoursodeoxycholic acid

Article abstract of DOI:10.1016/S0039-128X(84)80036-7

Homoursodeoxycholic acid and <11,12-³H>homoursodeoxycholic acid were synthesized from ursodeoxycholic acid and homocholic acid, respectively.Ursodeoxycholic acid (Ia) was converted to 3α,7β-diformoxy-5β-cholan-24-oic acid (Ib) using formic acid.Reaction of the diformoxy derivative (Ib) with thionyl chloride yielded the acid chloride (II) which was treated with diazomethane to produce 3α,7β-diformoxy-25-diazo-25-homo-5β-cholan-24-one (III).Homoursodeoxycholic acid (IV) was formed from the diazoketone (III) by means of the Wolff rearrangement of the Arndt-Eistert synthesis.N-Bromosuccinimide oxidation of homocholic acid (V), which was prepared from cholic acid by the same procedure described above, afforded 3α,12α-dihydroxy-7-oxo-25-homo-5β-cholan-25-oic acid (VI).Reduction of the 7-ketohomodeoxycholic acid (VI) with sodium in 1-propanol gave 3α,7β,12α-trihydroxy-25-homo-5β-cholan-25-oic acid (VII).The methyl ester of 7-epihomocholic acid (VII) was partially acetylated to give methyl 3α,7β-diacetoxy-12α-hydroxy-25-homo-5β-cholan-25-oate (VIII) using a mixture of acetic anhydride, pyridine and benzene.Dehydration of the diacetoxy derivative (VIII) with phosphorus oxychloride yielded methyl 3α,7β-diacetoxy-25-homo-5β-chol-11-en-25-oate (IX).Reduction of the unsaturated ester (IX) with tritium gas in the presence of platinum oxide catalyst followed by alkaline hydrolysis gave <11,12-³H>homoursodeoxycholic acid.