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【结 构 式】 
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【分子编号】62205 【品名】(5R,7R,10S,13R,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one 【CA登记号】 |
【 分 子 式 】C27H46O3 【 分 子 量 】418.66044 【元素组成】C 77.46% H 11.07% O 11.46% |
合成路线1
该中间体在本合成路线中的序号：(XIII)The oxidation of chenodeoxycholanic acid methyl ester (I) by known methods gives the 3-oxo derivative (II), which is treated with CH2(OMe)2 and P2O5 in chloroform to yield the 7-O-Mom protected compound (III). The reaction of (III) with ethyleneglycol and TsOH in refluxing benzene affords the ethyleneketal (IV), whose ester group is reduced with LiAlH4 in THF to provide the pentanol derivative (V). The oxidation of (V) with oxalyl chloride and DMSO in dichloromethane gives the aldehyde (VI), which is condensed with the phosphonium iodide (VII) by means of BuLi in THF to yield steroid (VIII) with an unsaturated side chain. The dihydroxylation of (VIII) by means of (DHQD)2PHAL, K2OsO2(OH)4 and K3Fe(CN)6 affords the 24(R),25-dihydroxysteroid (IX), which is monoacylated with Ac2O and pyridine to provide the monoacetate (X). The dehydration of (X) by means of MsCl and TEA gives the unsaturated acetoxy compound (XI), which is reduced and hydrolyzed by means of hydroxylamine and KOH to yield the 24(R)-hydroxysteroid (XII). Elimination of the ethylene ketal and Mom protecting groups of (XII) by means of TsOH in t-butanol affords the ketosteroid (XIII).
| 【1】 Zhou, X.D.; et al.; A stereoselective synthesis of squalamine. Tetrahedron 2002, 58, 52, 10293. |
| 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) | 62193 | (3R,5S,7R,10R,13R,17R)-17-[(1R)-4-ethyl-1-methyl-4-pentenyl]-3,5,7,10,13-pentamethylhexadecahydro-1H-cyclopenta[a]phenanthrene | C30H52 | 详情 | 详情 | |
| (II) | 62194 | (5R,7R,10R,13R,17R)-17-[(1R)-4-ethyl-1-methyl-4-pentenyl]-5,7,10,13-tetramethyl-3-methylenehexadecahydro-1H-cyclopenta[a]phenanthrene | C30H50 | 详情 | 详情 | |
| (III) | 62195 | (5R,7R,10R,13R,17R)-7-ethyl-17-[(1R)-4-ethyl-1-methyl-4-pentenyl]-5,10,13-trimethyl-3-methylenehexadecahydro-1H-cyclopenta[a]phenanthrene | C31H52 | 详情 | 详情 | |
| (IV) | 62196 | C29H48O6 | 详情 | 详情 | ||
| (V) | 62197 | C28H48O5 | 详情 | 详情 | ||
| (VI) | 62198 | C28H46O5 | 详情 | 详情 | ||
| (VII) | 62199 | Isopropyltriphenylphosphonium iodide; Isopropyltriphenylphosphonium iodide; Isopropyl triphenylphosphonium iodide; (2-Propyl)triphenylphosphonium bromide | 24470-78-8 | C21H22IP | 详情 | 详情 |
| (VIII) | 62200 | C31H52O4 | 详情 | 详情 | ||
| (IX) | 62201 | C31H54O6 | 详情 | 详情 | ||
| (X) | 62202 | C33H56O7 | 详情 | 详情 | ||
| (XI) | 62203 | C33H54O6 | 详情 | 详情 | ||
| (XII) | 62204 | C31H54O5 | 详情 | 详情 | ||
| (XIII) | 62205 | (5R,7R,10S,13R,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | C27H46O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIII)The reductocondensation of (XIII) with protected amine (XIV) by means of NaBH4 in methanol gives a mixture of the 3-beta and 3-alpha steroids, easily separated by flash chromatography. The desired 3-beta isomer (XV) is deprotected by means of HCl in methanol, yielding intermediate (XVI), which is finally treated with SO3 and pyridine to afford the target 24(R)-O-sulfate steroid
| 【1】 Zhou, X.D.; et al.; A stereoselective synthesis of squalamine. Tetrahedron 2002, 58, 52, 10293. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 62205 | (5R,7R,10S,13R,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | C27H46O3 | 详情 | 详情 | |
| (XIV) | 53724 | tert-butyl 3-aminopropyl{4-[(tert-butoxycarbonyl)amino]butyl}carbamate | n/a | C17H35N3O4 | 详情 | 详情 |
| (XV) | 62206 | tert-butyl 4-[(tert-butoxycarbonyl)amino]butyl[3-({(3S,5S,7R,10S,13R,17R)-7-hydroxy-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl}amino)propyl]carbamate | C44H81N3O6 | 详情 | 详情 | |
| (XVI) | 62207 | (3S,5S,7R,10S,13R,17R)-3-({3-[(4-aminobutyl)amino]propyl}amino)-17-[(1R,4R)-4-hydroxy-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-7-ol | C34H65N3O2 | 详情 | 详情 |