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【结 构 式】 
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【分子编号】49367 【品名】9H-fluoren-9-ylmethyl 3-([(1S)-1-[([(1S)-2-[((1S)-1-[[((2S,3S,4S,6R)-6-[[(1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy]-3-hydroxy-2-methyltetrahydro-2H-pyran-4-yl)amino]carbonyl]-3-methylbutyl)amino]-1-methyl-2-oxoethyl]amino)carbonyl]-3-methylbutyl]amino)-3-oxopropylcarbamate 【CA登记号】 |
【 分 子 式 】C60H71N5O17 【 分 子 量 】1134.24724 【元素组成】C 63.54% H 6.31% N 6.17% O 23.98% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of doxorubicin (I) with Fmoc-beta-alanyl-L-leucyl-L-alanyl-L-leucine (II) by means of HATU and DIEA in DMF gives the protected adduct (III), which is treated with piperidine in DMF to yield the deprotected adduct (IV). Finally, this compound is condensed with succinic anhydride (V) in the same solvent and treated with NaOH or NaHCO3 to afford the target sodium salt.
| 【1】 Fernandez, A.-M.; et al.; N-Succinyl-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin: An extracellularly tumor-activated prodrug devoid of intravenous acute toxicity. J Med Chem 2001, 44, 22, 3750. |
| 【2】 Lobl, T.J.; Trouet, A.; Fernandez, A.-M.; Nieder, M.H.; Yarranton, G.T.; Gangwar, S.; Viski, P.; Lewis, E.; Dubois, V. (Beckman Coulter, Inc.); Prodrug cpds. and process for preparation thereof. WO 0033888 . |
| 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) | 49366 | (9S,12S,15S)-1-(9H-fluoren-9-yl)-9,15-diisobutyl-12-methyl-3,7,10,13-tetraoxo-2-oxa-4,8,11,14-tetraazahexadecan-16-oic acid | C33H44N4O7 | 详情 | 详情 | |
| (II) | 11675 | (8S,10S)-10-[[(2R,4S,5S,6S)-4-Amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-glycoloyl-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C27H29NO11 | 详情 | 详情 | |
| (III) | 49367 | 9H-fluoren-9-ylmethyl 3-([(1S)-1-[([(1S)-2-[((1S)-1-[[((2S,3S,4S,6R)-6-[[(1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy]-3-hydroxy-2-methyltetrahydro-2H-pyran-4-yl)amino]carbonyl]-3-methylbutyl)amino]-1-methyl-2-oxoethyl]amino)carbonyl]-3-methylbutyl]amino)-3-oxopropylcarbamate | C60H71N5O17 | 详情 | 详情 | |
| (IV) | 49368 | (2S)-2-[(3-aminopropanoyl)amino]-N-[(1S)-2-[((1S)-1-[[((2S,3S,4S,6R)-6-[[(1S,3S)-3-glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy]-3-hydroxy-2-methyltetrahydro-2H-pyran-4-yl)amino]carbonyl]-3-methylbutyl)amino]-1-methyl-2-oxoethyl]-4-methylpentanamide | C45H61N5O15 | 详情 | 详情 | |
| (V) | 11291 | Dihydro-2,5-furandione; Succinic anhydride | 108-30-5 | C4H4O3 | 详情 | 详情 |