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【结 构 式】 
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【分子编号】29380 【品名】allyl (E)-amino[(3S)-2-[(6-amino-6-oxohexyl)oxy]-3-[(tert-butoxycarbonyl)amino]piperidinyl]methylidenecarbamate 【CA登记号】 |
【 分 子 式 】C21H37N5O6 【 分 子 量 】455.55488 【元素组成】C 55.37% H 8.19% N 15.37% O 21.07% |
合成路线1
该中间体在本合成路线中的序号：(IX)The title compound has been prepared by either solid-phase or solution-phase synthesis. In the first case, N(alpha)-Boc-N(omega)-nitro-L-arginine (I) was coupled with N,O-dimethylhydroxylamine, and the resulting N-methoxy-amide (II) was reduced with LiAlH4 to the corresponding aldehyde, isolated as the cyclic hemiaminal (III). Deprotection of the N-nitro group of (III) by hydrogenation over Pd/C afforded guanidine (IV), which was condensed with allyl chloroformate to give the allyl carbamate (V). Subsequent acid-catalyzed condensation with ethyl 6-hydroxyhexanoate (VI) at the aminal hydroxyl group provided ketal (VII). After hydrolysis of the ethyl ester of (VII), the resulting carboxylic acid (VIII) was coupled to amino-resin to produce the amide-resin (IX).
| 【1】 Cohen, C.R.; Weinhouse, M.I.; Roberts, C.; et al.; Synthesis and biological activity of transition-state urokinase inhibitors. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 090. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 38115 | 3-[(chlorocarbonyl)oxy]-1-propene | 2937-50-0 | C4H5ClO2 | 详情 | 详情 | |
| (I) | 29372 | N-alpha-(tert-butoxycarbonyl)-N-omega'-nitro-L-arginine | C11H21N5O6 | 详情 | 详情 | |
| (II) | 29373 | N-alpha-(tert-butoxycarbonyl)-N1-methoxy-N1-methyl-N-omega'-nitro-L-argininamide | C13H26N6O6 | 详情 | 详情 | |
| (III) | 29374 | 3(S)-(Tert-butoxycarbonylamino)-2-hydroxy-N2-nitropiperidine-1-carboxamidine | C11H21N5O5 | 详情 | 详情 | |
| (IV) | 29375 | tert-butyl (3S)-1-[amino(imino)methyl]-2-hydroxypiperidinylcarbamate | C11H22N4O3 | 详情 | 详情 | |
| (V) | 29376 | allyl (E)-amino[(3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxypiperidinyl]methylidenecarbamate | C15H26N4O5 | 详情 | 详情 | |
| (VI) | 29377 | ethyl 6-hydroxyhexanoate | C8H16O3 | 详情 | 详情 | |
| (VII) | 29378 | ethyl 6-([(3S)-1-[[[(allyloxy)carbonyl]imino](amino)methyl]-3-[(tert-butoxycarbonyl)amino]piperidinyl]oxy)hexanoate | C23H40N4O7 | 详情 | 详情 | |
| (VIII) | 29379 | 6-([(3S)-1-[[[(allyloxy)carbonyl]imino](amino)methyl]-3-[(tert-butoxycarbonyl)amino]piperidinyl]oxy)hexanoic acid | C21H36N4O7 | 详情 | 详情 | |
| (IX) | 29380 | allyl (E)-amino[(3S)-2-[(6-amino-6-oxohexyl)oxy]-3-[(tert-butoxycarbonyl)amino]piperidinyl]methylidenecarbamate | C21H37N5O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Further solid-phase peptide synthesis by means of sequential coupling of resin (IX) with L-alanine, D-serine and isobutyl chloroformate yielded the peptide-resin (X). The allyloxycarbonyl group of (X) was then removed by treatment with morpholine and palladium catalyst to give resin (XI). The target peptide was finally liberated from the resin (XI) by treatment with trifluoroacetic acid.
| 【1】 Cohen, C.R.; Weinhouse, M.I.; Roberts, C.; et al.; Synthesis and biological activity of transition-state urokinase inhibitors. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 090. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 29380 | allyl (E)-amino[(3S)-2-[(6-amino-6-oxohexyl)oxy]-3-[(tert-butoxycarbonyl)amino]piperidinyl]methylidenecarbamate | C21H37N5O6 | 详情 | 详情 | |
| (X) | 29381 | allyl (E)-amino((3S)-2-[(6-amino-6-oxohexyl)oxy]-3-[[(2S)-2-([(2R)-3-hydroxy-2-[(isobutoxycarbonyl)amino]propanoyl]amino)propanoyl]amino]piperidinyl)methylidenecarbamate | C27H47N7O9 | 详情 | 详情 | |
| (XI) | 29382 | isobutyl (1R)-2-[[(1S)-2-([(3S)-1-[amino(imino)methyl]-2-[(6-amino-6-oxohexyl)oxy]piperidinyl]amino)-1-methyl-2-oxoethyl]amino]-1-(hydroxymethyl)-2-oxoethylcarbamate | C23H43N7O7 | 详情 | 详情 |