Ro-25-4020
Chemical Name: (5,6-trans)-1alpha,25-Dihydroxy-16,17-didehydrovitamin D3; 9,10-Secocholesta-5(E),7(E),10(19),16,tetraene-1alpha,3beta,25-triol
CAS No. 247244-88-8
项目整合开发状态: Preclinical
项目研究机构: Roche (Originator)
合成路线:Oxidation of hydroxylated diene (I) with m-CPBA followed by acetylation provides epoxide (II),which is then converted to the corresponding hydroxy derivative (III) by means of SeO2 and PyO in dioxane followed by isomer separation.Treatment of compound (III) with t-butyldimethylsilyl chloride and imidazole in DMF yields the 5,7-bis-protected derivative (IV),which reacts in THF with tungsten hexachloride (WCl6) and BuLi in hexane/THF to furnish compound (V).Hydrolysis of acetate (V) with NaOH in MeOH provides alcohol (VI),which is then converted into the corresponding chloro derivative (VII) by treatment with N-chlorosuccinimide (NCS) and dimethylsulfide (Me2S) in CH2Cl2.Treatment of compound (VII) with potassium diphenylphosphide (PPh2K) in THF and aqueous H2O2 in CH2Cl2 gives diphenylphosphine oxide (VIII),which is condensed in THF with hexahydro indenone derivative (IX) by means of n-BuLi in hexane to afford compound (X).Finally,derivative (X) is deprotected by treatment with tetrabutyl ammonium fluoride in THF to yield the desired product.
📌 参考资料/链接：
参考文献标题:Vitamin D3 analogs
文献作者:Batcho,A.D.; Hennessy,B.M.; Uskokovic,M.R.(F.Hoffmann-La Roche AG)
参考来源:WO 0104089
📄 详细内容
合成路线:Oxidation of hydroxylated diene (I) with m-CPBA followed by acetylation provides epoxide (II),which is then converted to the corresponding hydroxy derivative (III) by means of SeO2 and PyO in dioxane followed by isomer separation.Treatment of compound (III) with t-butyldimethylsilyl chloride and imidazole in DMF yields the 5,7-bis-protected derivative (IV),which reacts in THF with tungsten hexachloride (WCl6) and BuLi in hexane/THF to furnish compound (V).Hydrolysis of acetate (V) with NaOH in MeOH provides alcohol (VI),which is then converted into the corresponding chloro derivative (VII) by treatment with N-chlorosuccinimide (NCS) and dimethylsulfide (Me2S) in CH2Cl2.Treatment of compound (VII) with potassium diphenylphosphide (PPh2K) in THF and aqueous H2O2 in CH2Cl2 gives diphenylphosphine oxide (VIII),which is condensed in THF with hexahydro indenone derivative (IX) by means of n-BuLi in hexane to afford compound (X).Finally,derivative (X) is deprotected by treatment with tetrabutyl ammonium fluoride in THF to yield the desired product.
参考文献标题:Chemical conversion of vitamin D3 to its 1,25-dihydroxy metabolite
文献作者:Kiegiel,J.; et al.
参考来源:Tetrahedron Lett 1991,32(43),6057