(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 -Drug Synthesis Database

【结构式】

【分子编号】48093

【品名】(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

【CA登记号】128-13-2

【分子式】C₂₄H₄₀O₄

【分子量】392.5792

【元素组成】C 73.43% H 10.27% O 16.3%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

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

合成目标

【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

该中间体在本合成路线中的序号：(I)

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

合成目标

【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

该中间体在本合成路线中的序号：(III)

Ferulic acid (I) was converted to the 4-bromobutyl ester (II) upon treatment with carbon tetrabromide, triphenylphosphine and THF also as the solvent. Coupling of dihydroxycholanoic acid (III) with ferulic acid bromobutyl ester (II) using DCC in the presence of DMAP furnished diester (IV). Finally, displacement of the bromide group of (IV) with silver nitrate gave rise to the title nitrooxy derivative.

参考文献中间体

合成目标

【1】 Del Soldato, P. (NicOx SA); Pharmaceutical cpds.. WO 0061604 .

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)	48091	(E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid	1135-24-6	C₁₀H₁₀O₄	详情	详情
(II)	48092	4-bromobutyl (E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate		C₁₄H₁₇BrO₄	详情	详情
(III)	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
(IV)	48094	4-bromobutyl (E)-3-[4-([(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]oxy)-3-methoxyphenyl]-2-propenoate		C₃₈H₅₅BrO₇	详情	详情

Extended Information