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【结 构 式】 
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【分子编号】64281 【品名】(7S)-5-(tert-butoxycarbonyl)-7-(4-{[tert-butyl(dimethyl)silyl]oxy}benzyl)-2,2,11,11-tetramethyl-4,6,9-trioxo-3,10-dioxa-5,8-diazadodecane 【CA登记号】 |
【 分 子 式 】C30H50N2O8Si 【 分 子 量 】594.82118 【元素组成】C 60.58% H 8.47% N 4.71% O 21.52% Si 4.72% |
合成路线1
该中间体在本合成路线中的序号：(V)N-Boc-L-Tyrosine (I) methyl ester is treated with methanolic ammonia to provide amide (II). Protection of the phenolic hydroxyl of (II) with t-butyldimethylsilyl chloride leads to the silyl ether (III), which is further reacted with di-t-butyl dicarbonate in the presence of DMAP to furnish the tri-Boc derivative (IV). Subsequent desilylation of (IV) by means of tetrabutylammonium fluoride affords the tri-Boc-tyrosinamide (V).
| 【1】 Peyrottes, S.; Coussot, G.; Lefebvre, I.; Imbach, J.-L.; Gosselin, G.; Aubertin, A.-M.; Perigaud, C.; S-acyl-2-thioethyl aryl phosphotriester derivatives of AZT: Synthesis, antiviral activity, and stability study. J Med Chem 2003, 46, 5, 782. |
| 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) | 19875 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propanoate | 4326-36-7 | C15H21NO5 | 详情 | 详情 |
| (II) | 64278 | tert-butyl (1S)-2-amino-1-(4-hydroxybenzyl)-2-oxoethylcarbamate | C14H20N2O4 | 详情 | 详情 | |
| (III) | 64279 | tert-butyl (1S)-2-amino-1-(4-{[tert-butyl(dimethyl)silyl]oxy}benzyl)-2-oxoethylcarbamate | C20H34N2O4Si | 详情 | 详情 | |
| (IV) | 64280 | C25H38N2O8 | 详情 | 详情 | ||
| (V) | 64281 | (7S)-5-(tert-butoxycarbonyl)-7-(4-{[tert-butyl(dimethyl)silyl]oxy}benzyl)-2,2,11,11-tetramethyl-4,6,9-trioxo-3,10-dioxa-5,8-diazadodecane | C30H50N2O8Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Tetrazole-catalyzed phosphitylation of the tyrosinamide derivative (V) with O-2-(pivaloylthio)ethyl-N,N,N',N'-tetraisopropylphosphorodiamidite (VI) yields phosphoramidite (VII). This is subsequently coupled to azidothimidine (VIII) to furnish phosphite (IX), which is then oxidized to the corresponding phosphate (X) with t-butyl hydroperoxide. The N-Boc protecting groups of (X) are finally removed under acidic conditions to provide the title compound.
| 【1】 Peyrottes, S.; Coussot, G.; Lefebvre, I.; Imbach, J.-L.; Gosselin, G.; Aubertin, A.-M.; Perigaud, C.; S-acyl-2-thioethyl aryl phosphotriester derivatives of AZT: Synthesis, antiviral activity, and stability study. J Med Chem 2003, 46, 5, 782. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 64281 | (7S)-5-(tert-butoxycarbonyl)-7-(4-{[tert-butyl(dimethyl)silyl]oxy}benzyl)-2,2,11,11-tetramethyl-4,6,9-trioxo-3,10-dioxa-5,8-diazadodecane | C30H50N2O8Si | 详情 | 详情 | |
| (VI) | 64282 | S-(2-{[bis(diisopropylamino)phosphino]oxy}ethyl) 2,2-dimethylpropanethioate | C19H41N2O2PS | 详情 | 详情 | |
| (VII) | 64283 | (7S)-5-(tert-butoxycarbonyl)-7-{4-[((diisopropylamino){2-[(2,2-dimethylpropanoyl)sulfanyl]ethoxy}phosphino)oxy]benzyl}-2,2,11,11-tetramethyl-4,6,9-trioxo-3,10-dioxa-5,8-diazadodecane | C37H62N3O10PS | 详情 | 详情 | |
| (VIII) | 25317 | 1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | 101703-35-9 | C10H13N5O4 | 详情 | 详情 |
| (IX) | 64284 | 1-{(2R,4S,5S)-4-azido-5-[3-(4-{(2S)-3-[bis(tert-butoxycarbonyl)amino]-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)-9,9-dimethyl-8-oxo-2,4-dioxa-7-thia-3-phosphadec-1-yl]tetrahydro-2-furanyl}-5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine | C41H60N7O14PS | 详情 | 详情 | |
| (X) | 64285 | 1-{(2R,4S,5S)-4-azido-5-[3-(4-{(2S)-3-[bis(tert-butoxycarbonyl)amino]-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)-9,9-dimethyl-3,8-dioxo-2,4-dioxa-7-thia-3lambda~5~-phosphadec-1-yl]tetrahydro-2-furanyl}-5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine | C41H60N7O15PS | 详情 | 详情 |