10538-59-7Relevant articles and documents
Facial synthesis of key intermediate of obeticholic acid via Pd-catalyzed Kumada-Tamao-Corriu cross-coupling reaction
Di, Xiangjie,Han, Jie,Huang, Qingfei,Wang, Qiwei,Wang, Yuanhua,Wei, Xia,Zhong, Liu,Zhu, Jin,Zou, Sheng
, (2020)
Obeticholic acid (OCA) is used to treatment for Primary Biliary Cholangitis and other Famesoid X Receptor related diseases. Through the palladium catalyzed Kumada-Tamao-Corriu cross-coupling reaction, a novel and efficient method for synthesis of OCA with satisfied yield was successfully developed. The absolute configuration of the key intermediate was confirmed by Single-crystal X-ray Diffraction. It affords good strategy for large-scale synthesis of OCA.
BILE ACIDS LXIX. SELECTIVE K-SELECTRIDE REDUCTION OF 3,7-DIKETO STEROIDS
Tal, Daniel M.,Frisch, G. Douglas,Elliott, William H.
, p. 851 - 854 (1984)
The K-Selectride reduction at low temperature (-45 C) of 7-oxo-5α-cholestan-3β-yl acetate and methyl 7-oxo-3α-hydroxy-5β-cholanoate resulted in almost quantitative yield of the 7α-alcohol in the 5α-compound but only moderate yield of the 5β-analog.The simultaneous reduction of two carbonyl in the 3 and 7 positions afforded good to excellent yields of the diaxial diol in planar steroids (methyl 3,7-dioxo-5α-cholanoate, 3,7-dioxo-5α-cholestane and methyl 3,7-dioxo-5α-cholestan-27-oate) and only 14percent of 3α,7α-(OH)2 from methyl 3,7-dioxo-5β-cholanoate.
Method for preparing obeticholic acid
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Paragraph 0112-0114, (2021/08/19)
The invention discloses a method for preparing obeticholic acid or pharmaceutically acceptable salt thereof, the method comprises the following steps: (c) carrying out hydrolysis reaction on a compound 5 to remove a carboxyl protecting group Q so as to generate a compound 6; (d) subjecting the compound 6 to a hydrogenation reaction to produce a compound 7; (e) carrying out carbonyl reduction reaction and hydrolysis reaction for removing a hydroxyl protecting group P on the compound 7 by a one-step method to generate obeticholic acid, wherein P is a hydroxyl protecting group, and Q is a carboxyl protecting group. The key intermediate product in a solid form at normal temperature is obtained through design of a synthesis route, separation and purification of the intermediate product and subsequent synthesis operation are facilitated, and the yield of each step and the purity of the intermediate product and the final product are improved.
7-ketolithocholic acid intermediate and preparation process and application thereof
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Paragraph 0062; 0071; 0073; 0082, (2019/11/21)
The invention discloses a 7-ketolithocholic acid intermediate and a preparation process and an application thereof. Hyocholic acid is utilized as a starting material, an esterification reaction is carried out first, then a silane protection group protects a 3-hydroxyl group with high selectivity, then a specific spatial structure of 6,7-hydroxyl group of the hyocholic acid is utilized, a conventional protection method can be selectively connected to a strong leaving group at 6-position to obtain the 7-ketolithocholic acid intermediate, and the 7-ketolithocholic acid intermediate is subjected to oxidation, removal, reduction, and hydrolysis to remove a protection group to obtain a target product 7-ketolithocholic acid. The 7-ketolithocholic acid prepared by the process is high in degree ofpurity, is also simple in process step, enables a synthetize route to be greatly simplified, and enables the industrialization cost to be saved.
