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【结 构 式】 
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【分子编号】32054 【品名】methyl 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-phenoxy-1-butenyl]cyclopentyl]-4,5-heptadienoate 【CA登记号】 |
【 分 子 式 】C23H30O6 【 分 子 量 】402.4876 【元素组成】C 68.64% H 7.51% O 23.85% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The acetylation of (XIII) with acetic anhydride and triethylamine in methylene chloride yields the diacetoxy-bistetra-hydropyranyloxy acetylenic compound (XlV), which by a treatment with Cu2Br2-LiCH3 in ether is converted into 16-phenoxy-9alpha-acetoxy-11alpha,15alpha-bistetrahydropyranyloxy-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acid methyl ester (XV). Elimination of the tetrahydropyranyl groups with acetic acid in water gives the corresponding dihydroxy compound (XVI), which is fully deprotected with K2CO3 in methanol yielding 9alpha,11alpha,15alpha-trihydroxy-16-phenoxy-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acid (XVII). The methylation of (XVII) with diazomethane affords the corresponding methyl ester (XVIII), which by treatment with tert-butyldimethylsilyl chloride (XIX) in DMF is converted into the corresponding 11,15-bis(silyloxy) compound (XX). The oxidation of (XX) with CrO3 - pyridine in CH2Cl2 affords 9-oxo-16-phenoxy-11alpha,15alpha-bis(tert-butyldimethylsilyloxy)-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acid methyl ester (XXI), which is deprotected with aqueous acetic acid giving the free keto ester (XXII). Finally, this ester is hydrolyzed by treatment with pancreatic lipase.
| 【1】 Van Horn, A.R.; Garay, G.; Edwards, J.A. (Syntex (USA), Inc.); (dl)-16-Phenoxy- and 16-substituted phenoxy-9-keto prostatrienoic acid derivatives and processes for the production thereof. DE 2927715; EP 0008003; ES 482330; FR 2430939; GB 2025413; US 4178457 . |
| 【2】 Muchowski, J.M.; Fried, J.H. (Syntex (USA), Inc.); 16-Phenoxy and 16-substituted phenoxy-prostatrienoic acid derivatives. DE 2627910; ES 449162; FR 2315263; US 3985791 . |
| 【3】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Hillier, K.; RS-84,135. Drugs Fut 1982, 7, 11, 812. |
| 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) | 32049 | methyl 6-hydroxy-7-[(1R,2S,3R,5S)-5-hydroxy-2-[(E,3R)-4-phenoxy-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-4-heptynoate | C35H50O9 | 详情 | 详情 | |
| (XIV) | 32050 | methyl 6-(acetoxy)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E,3R)-4-phenoxy-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-4-heptynoate | C39H54O11 | 详情 | 详情 | |
| (XV) | 32051 | methyl 7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E,3R)-4-phenoxy-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-4,5-heptadienoate | C37H52O9 | 详情 | 详情 | |
| (XVI) | 32052 | methyl 7-[(1R,2R,3R,5S)-5-(acetoxy)-3-hydroxy-2-[(E,3R)-3-hydroxy-4-phenoxy-1-butenyl]cyclopentyl]-4,5-heptadienoate | C25H32O7 | 详情 | 详情 | |
| (XVII) | 32053 | 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-phenoxy-1-butenyl]cyclopentyl]-4,5-heptadienoic acid | C22H28O6 | 详情 | 详情 | |
| (XVIII) | 32054 | methyl 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-phenoxy-1-butenyl]cyclopentyl]-4,5-heptadienoate | C23H30O6 | 详情 | 详情 | |
| (XIX) | 32057 | tert-butyl(chloro)dimethylsilane | 18162-48-6 | C6H15ClSi | 详情 | 详情 |
| (XX) | 32055 | methyl 7-[(1R,2R,3R,5S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-phenoxy-1-butenyl)-5-hydroxycyclopentyl]-4,5-heptadienoate | C35H58O6Si2 | 详情 | 详情 | |
| (XXI) | 32056 | methyl 7-[(1R,2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-phenoxy-1-butenyl)-5-oxocyclopentyl]-4,5-heptadienoate | C35H56O6Si2 | 详情 | 详情 |