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【结 构 式】 
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【分子编号】15842 【品名】(1S,2S)-2-[[(benzyloxy)carbonyl]amino]-1-([(4R)-4-[(tert-butylamino)carbonyl]-1,3-thiazolidin-3-yl]carbonyl)-3-phenylpropyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-(methylsulfanyl)propanoate 【CA登记号】 |
【 分 子 式 】C35H48N4O8S2 【 分 子 量 】716.92028 【元素组成】C 58.64% H 6.75% N 7.81% O 17.85% S 8.95% |
合成路线1
该中间体在本合成路线中的序号：(X)2) The intermediate (V) of the preceding synthesis is submitted to a deprotection - protection sequence [hydrolysis with HCl in dioxane and protection with benzyl succinimidyl carbonate (PhCH2-OSu)] giving the benzyloxycarbonyl protected compound (IX), which is condensed with (VI) by means of DCC and dimethylaminopyridine (DMAP) to yield (X) [the ester isomer of (VII)]. The deprotection of (X) with HCl and condensation with (VIII) by means of HBOT and DCC as before affords (XI) [the benzyloxycarbonyl protected prodrug of KNI-272], which is deprotected with trifluoroacetic acid (TFA)/anisole and HCl affording the ester prodrug (XII). Finally, this compound is converted into KNI-272 by incubation at 37 C in a phosphate buffered saline at pH 7.4.
| 【1】 Kimura, T.; Ohtake, J.; Nakata, S.; Enomoto, H.; Moriwaki, H.; Akaji, K.; Kiso, Y.; Synthesis and prodrugs of HIV protease inhibitors. Peptide Chem 1994, 157-60. |
| 【2】 Ireland, C.D.; Castaner, J.; KNI-272. Drugs Fut 1996, 21, 10, 1022. |
| 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) | 15837 | tert-Butyl N-((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-1,3-thiazolan-3-yl]-2-hydroxy-3-oxopropyl)carbamate | C23H35N3O5S | 详情 | 详情 | |
| (VI) | 15838 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(methylsulfanyl)propionic acid | C9H17NO4S | 详情 | 详情 | |
| (VIII) | 15840 | 2-(5-isoquinolinyloxy)acetic acid | C11H9NO3 | 详情 | 详情 | |
| (IX) | 15841 | benzyl N-((1S,2S)-1-benzyl-3-[(4R)-4-[(tert-butylamino)carbonyl]-1,3-thiazolan-3-yl]-2-hydroxy-3-oxopropyl)carbamate | C26H33N3O5S | 详情 | 详情 | |
| (X) | 15842 | (1S,2S)-2-[[(benzyloxy)carbonyl]amino]-1-([(4R)-4-[(tert-butylamino)carbonyl]-1,3-thiazolidin-3-yl]carbonyl)-3-phenylpropyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-(methylsulfanyl)propanoate | C35H48N4O8S2 | 详情 | 详情 | |
| (XI) | 15843 | (1S,2S)-2-[[(benzyloxy)carbonyl]amino]-1-([(4R)-4-[(tert-butylamino)carbonyl]-1,3-thiazolidin-3-yl]carbonyl)-3-phenylpropyl (2R)-2-[[2-(5-isoquinolinyloxy)acetyl]amino]-3-(methylsulfanyl)propanoate | C41H47N5O8S2 | 详情 | 详情 | |
| (XII) | 15844 | (1S,2S)-2-amino-1-([(4R)-4-[(tert-butylamino)carbonyl]-1,3-thiazolidin-3-yl]carbonyl)-3-phenylpropyl (2R)-2-[[2-(5-isoquinolinyloxy)acetyl]amino]-3-(methylsulfanyl)propanoate | C33H41N5O6S2 | 详情 | 详情 |