Tauroursodeoxycholic acid, Ursodeoxycholyltaurine, UR-906, -Drug Synthesis Database

【结构式】

【药物名称】Tauroursodeoxycholic acid, Ursodeoxycholyltaurine, UR-906

【化学名称】N-(3alpha,7beta-Dihydroxy-5beta-cholan-24-oyl)taurine

【CA登记号】14605-22-2

【分子式】C₂₆H₄₅NO₆S

【分子量】499.71565

【开发单位】Mitsubishi Pharma (Originator), Children's Hosp. Med. Center, Cincinnati (Codevelopment)

【药理作用】GASTROINTESTINAL DRUGS, Hepatoprotectants, Liver and Biliary Tract Disorders, Treatment of

合成路线1 合成路线2 合成路线3

合成路线1

Ursodeoxycholic acid (I) was activated as the mixed anhydride (II) with ethyl chloroformate and triethylamine, and subsequently coupled with the triethylamine salt of taurine (III) to produce the title conjugated bile acid. Optionally, the mixed anhydride (II) was previously converted to the active phenol ester (V) by treatment with p-hydroxypropiophenone (IV), and subsequently condensed with taurine (III). Alternatively, ursodeoxycholic acid (I) was directly coupled to taurine (III) employing as the coupling reagents 2-isobutyl-N-isobutyloxycarbonyl-1,2-dihydroquinoline (IIDQ), diethylphosphorocyanidate (DEPC), or 2-ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) under microwave irradiation.

参考文献中间体

【1】 Momose, T.; et al.; An improved synthesis of taurine- and glycine-conjugated bile acids. Lipids 1997, 32, 7, 775.
【2】 Dayal, B.; et al.; Microwave-induced rapid synthesis of bile acid conjugates. Synlett 1997, 8, 861.
【3】 Bonadi, A.; Molinari, E.; Process for the preparation of taurine-conjugated bile acids. EP 0582891 .
【4】 Reiner, A. (SkyePharma AG); Process for preparing ursodeoxycholic acid derivates and their inorganic and organic salts having therapeutic activity. EP 0272462 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	48093	(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	128-13-2	C₂₄H₄₀O₄	详情	详情
(II)	59137			C₂₇H₄₄O₆	详情	详情
(III)	34828	2-amino-1-ethanesulfonic acid	107-35-7	C₂H₇NO₃S	详情	详情
(IV)	58982	4'-Hydroxypropiophenone; 4-Hydroxypropiophenone; Ethyl 4-Hydroxyphenyl ktone; p-Hydroxypropiophenone; Paroxypropione	70-70-2	C₉H₁₀O₂	详情	详情
(V)	59138	4-propionylphenyl (4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate		C₃₃H₄₈O₅	详情	详情

合成路线2

In a related method, ursodeoxycholic acid (I) was activated as either the mixed anhydrides (VI) or (VII) with pivaloyl chloride or benzoyl chloride, respectively. Subsequent coupling with taurine (III) produced the title conjugated bile acid.

参考文献中间体

【1】 Rossetti, V.; Arosio, R. (Sanofi-Synthelabo); Process for the preparation of taurocholic acids. EP 0629634 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	48093	(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	128-13-2	C₂₄H₄₀O₄	详情	详情
(III)	34828	2-amino-1-ethanesulfonic acid	107-35-7	C₂H₇NO₃S	详情	详情
(VI)	59139	(4R)-3-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic 1,1-dimethylpropanoic anhydride		C₂₉H₄₈O₅	详情	详情
(VII)	59140	1-benzenecarboxylic (4R)-3-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic anhydride		C₃₁H₄₄O₅	详情	详情

合成路线3

A further method was based on the microbial hydroxylation of taurolithocholic acid (VIII) by the action of a microorganism belonging to the Mortierella genus.

参考文献中间体

【1】 Sawada, H.; Watanuki, M. (Yakult Honsha Co., Ltd.); Procuding conjugated ursodeoxycholic acids. EP 0119040 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	59141	2-({(4R)-4-[(3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl}amino)-1-ethanesulfonic acid		C₂₆H₄₅NO₅S	详情	详情

Extended Information