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【结 构 式】 
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【分子编号】34238 【品名】ethyl 4-[(1S,4R,5R)-5-[(benzyloxy)methyl]-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-cyclopenten-1-yl]-2-diazo-3-oxobutanoate 【CA登记号】 |
【 分 子 式 】C25H32N2O6 【 分 子 量 】456.53896 【元素组成】C 65.77% H 7.06% N 6.14% O 21.03% |
合成路线1
该中间体在本合成路线中的序号：(XX)The protection of hydroxyester (II) with dihydropyran dihydropyran and p-toluene sulfonic acid in methylene chloride gives 1-(tetrahydropyranyloxy)-4-methoxycarbonylmethyl-6-benzyloxymethylcyclopent-2-ene (XVIII), which is condensed with ethyl acetate by means of butyllithium and diisopropyl amine in THF yielding 1-(tetrahydropyranyloxy)-4-(2-oxo-3-ethoxycarbonylpropyl)-5-benzyloxymethylcyclopent-2-ene (XIX). The reaction of (XIX) with p-toluenesulfonyl azide and triethylamine in acetonitrile affords 1-(tetrahydropyranyloxy)-4-(2-oxo-3-diazo-3-ethoxycarbonylpropyl)-5-benzyloxymethylcyclopent-2-ene (XX), which is cyclized by means of CuSO4 in refluxing benzene to 2-ethoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-tricyclo[3.3.0.0(2,8)]octan-3-one (XXI). Ring opening of (XXI) with tributyltin hydride and azobisisobutyronitrile in benzene irradiated with UV light affords 2-ethoxycarbonyl-6-benzyloxymethyl-7-(tetrahydropyranyloxy)-cis-bicyclo[3.3.0]octan-3-one (XXII), which is hydrolyzed and decarboxylated in HMPT - water at 160 C giving (VIII), already obtained.
| 【1】 Hayashi, M.; Konishi, Y.; Arai, Y.; 6,9-Methano-PGI2 analogues. CH 639360; DE 2912409; FR 2422635; GB 2017699; IT 1113341; US 4479966 . |
| 【2】 Kottegoda, S.R.; Serradell, M.N.; Adaikan, P.G.; Castaner, J.; ONO-41483. Drugs Fut 1984, 9, 11, 833. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 34222 | methyl 2-[(1S,4R,5S)-5-[(benzyloxy)methyl]-4-hydroxy-2-cyclopenten-1-yl]acetate | C16H20O4 | 详情 | 详情 | |
| (VIII) | 34227 | (3aS,4R,5R,6aR)-4-[(benzyloxy)methyl]-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]hexahydro-2(1H)-pentalenone | C22H30O4 | 详情 | 详情 | |
| (XVIII) | 34236 | methyl 2-[(1S,4R,5R)-5-[(benzyloxy)methyl]-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-cyclopenten-1-yl]acetate | C22H30O5 | 详情 | 详情 | |
| (XIX) | 34237 | ethyl 4-[(1S,4R,5R)-5-[(benzyloxy)methyl]-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-cyclopenten-1-yl]-3-oxobutanoate | C25H34O6 | 详情 | 详情 | |
| (XX) | 34238 | ethyl 4-[(1S,4R,5R)-5-[(benzyloxy)methyl]-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]-2-cyclopenten-1-yl]-2-diazo-3-oxobutanoate | C25H32N2O6 | 详情 | 详情 | |
| (XXI) | 34239 | ethyl (2bR,3R,4R,4aS,4bR)-4-[(benzyloxy)methyl]-2-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]hexahydrocyclopropa[cd]pentalene-2a(2H)-carboxylate | C25H32O6 | 详情 | 详情 | |
| (XXII) | 34240 | ethyl (1R,3aS,4R,5R,6aS)-4-[(benzyloxy)methyl]-2-oxo-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]octahydro-1-pentalenecarboxylate | C25H34O6 | 详情 | 详情 |