| Ursodeoxycholic acid (UDCA) is currently indicated for the only medicinein the world which can treat the patients with primary biliary cirrhosis andprimary sclerosing cholangitis. Traditional method to obtain this compound isextracted from bear bile. Because of limited sources, and contrary to animalprotection, synthetic UDCA has become a research hotspot.By analyzing a large number of documents, we proposed a method tosynthesis UDCA starting from sterols which are inexpensive and readily available.In this method, inversion of hydroxyl group (C-3position) and stereoseletivereduction of C=C double bond are the key steps to synthesis UDCA. In this paper,3α-cholesterol and four isomers of5-cholestan-3-ol were synthesized to renderthese two reactions, and these steroids are also the important intermediates indrug synthesis.On the basis of traditional synthesis methods, this paper designs and triesthree synthetic routes to synthesis3α-cholesterol. In the end,3α-cholesterol wassynthesized from3β-cholesterol via three steps involving mesylation, SN2acetylation, and hydrolysis reactions. In this paper, the systematic study of SN2acetylation reaction has been done. Acetylation reagent, phase transfer catalystand solvent were examined on the acetylation reaction. Carboxylate salts of alkalimetals, alkaline-earth metals and transition metals, and tunable complex ofHOAc-R3N were tried as acetylation reagents.Synthesis of four isomers of5-cholestan-3-ol: two5α-dihydroxy isomers,5α-cholestan-3β-ol (4) and5α-cholestan-3α-ol (5) were synthesized by hydrogen-ation of3β-cholesterol and3α-cholesterol under Pd/C catalyst. And the structuresof these two compounds have been characterized by1H NMR. Two5β-dihydroxy isomers were synthesized by reduction of5β-cholestan-3-one. Eventually,5β-cholestan-3β-ol (8) and5β-cholestan-3α-ol (9) were got as a mixture in1:3analysed by1H NMR. |
