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【结 构 式】 
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【分子编号】58681 【品名】(3aR,5S,6aR)-5-{(1S)-2-azido-1-[(4-methoxybenzyl)oxy]ethyl}-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole; (1S)-1-[(3aR,5S,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-2-azidoethyl 4-methoxybenzyl ether 【CA登记号】 |
【 分 子 式 】C17H23N3O5 【 分 子 量 】349.38684 【元素组成】C 58.44% H 6.64% N 12.03% O 22.9% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of the epoxy-glucoside (I) with Tms-N3 in DMF gives the azido-glucoside (II), which is treated with Pmb-Cl and NaH in DMF to yield the aryl ether protected glucoside (III). The cleavage of the acetonide group of (III) by means of HOAc/water affords the dihydroxy compound (IV), which is acylated by means of Ac2O and pyridine to provide the diacetate (V). The condensation of (V) with uracil (VI) by means of BSA and Tms-Br in acetonitrile gives the uridine derivative (VII), which is reduced at its azido group by means of H2 over Pd/C in ethyl acetate to yield the amino derivative (VIII). The condensation of (VIII) with palmitic anhydride (IX) affords the corresponding amide (X), which is selectively deprotected by means of TFA to provide the alcohol (XI). The condensation of (XI) with 5-azido-5-deoxy-1,2,3-O-triacetyl-alpha-D-ribofuranose (XII) by means of SnCl4 in dichloromethane provides the uridine derivative (XIII), which is deacetylated by means of MeONa in methanol to give the azido precursor (XIV). Finally, the azido group of (XIV) is reduced by means of H2 over Pd/C in methanol to yield the target compound.
| 【1】 Dini, C.; et al.; Synthesis and in vitro evaluation of riburamycin RU75411: Activity against MraY, antibacterial profile, and mechanism of action (MOA) on whole cells. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-361. |
| 【2】 Aszodi, J.; Didierlaurent, S.; Dini, C.; Zhang, J.; Drochon, N.; Guillot, J.-C. (Aventis Pharma SA); Uridine derivs. as antibiotics. EP 1284984; WO 0185750 . |
| 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) | 58679 | (3aR,5S,6aR)-2,2-dimethyl-5-[(2S)oxiranyl]tetrahydrofuro[2,3-d][1,3]dioxole | C9H14O4 | 详情 | 详情 | |
| (II) | 58680 | (1S)-1-[(3aR,5S,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-2-azido-1-ethanol | C9H15N3O4 | 详情 | 详情 | |
| (III) | 58681 | (3aR,5S,6aR)-5-{(1S)-2-azido-1-[(4-methoxybenzyl)oxy]ethyl}-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole; (1S)-1-[(3aR,5S,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-2-azidoethyl 4-methoxybenzyl ether | C17H23N3O5 | 详情 | 详情 | |
| (IV) | 58682 | (2S,3R,5S)-5-{(1S)-2-azido-1-[(4-methoxybenzyl)oxy]ethyl}tetrahydro-2,3-furandiol | C14H19N3O5 | 详情 | 详情 | |
| (V) | 58683 | (2R,3R,5S)-2-(acetyloxy)-5-{(1S)-2-azido-1-[(4-methoxybenzyl)oxy]ethyl}tetrahydro-3-furanyl acetate | C18H23N3O7 | 详情 | 详情 | |
| (VI) | 30921 | 2,4(1H,3H)-pyrimidinedione; Uracil | 66-22-8 | C4H4N2O2 | 详情 | 详情 |
| (VII) | 58684 | (2R,3R,5S)-5-{(1S)-2-azido-1-[(4-methoxybenzyl)oxy]ethyl}-2-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-3-furanyl acetate | C20H23N5O7 | 详情 | 详情 | |
| (VIII) | 58685 | (2R,3R,5S)-5-{(1S)-2-amino-1-[(4-methoxybenzyl)oxy]ethyl}-2-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-3-furanyl acetate | C20H25N3O7 | 详情 | 详情 | |
| (IX) | 27916 | hexadecanoic anhydride | 623-65-4 | C32H62O3 | 详情 | 详情 |
| (X) | 58686 | (2R,3R,5S)-2-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-5-[(1S)-1-[(4-methoxybenzyl)oxy]-2-(palmitoylamino)ethyl]tetrahydro-3-furanyl acetate | C36H55N3O8 | 详情 | 详情 | |
| (XI) | 58687 | (2R,3R,5S)-2-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-5-[(1S)-1-hydroxy-2-(palmitoylamino)ethyl]tetrahydro-3-furanyl acetate | C28H47N3O7 | 详情 | 详情 | |
| (XII) | 58688 | (2R,3R,4R,5R)-2,4-bis(acetyloxy)-5-(azidomethyl)tetrahydro-3-furanyl acetate | C11H15N3O7 | 详情 | 详情 | |
| (XIII) | 58689 | (2R,3R,4R,5S)-4-(acetyloxy)-5-{[(1S)-1-{(2S,4R,5R)-4-(acetyloxy)-5-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}-2-(palmitoylamino)ethyl]oxy}-2-(azidomethyl)tetrahydro-3-furanyl acetate | C37H58N6O12 | 详情 | 详情 | |
| (XIV) | 58690 | N-((2S)-2-{[(2R,3R,4S,5R)-5-(azidomethyl)-3,4-dihydroxytetrahydro-2-furanyl]oxy}-2-{(2S,4R,5R)-5-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-4-hydroxytetrahydro-2-furanyl}ethyl)hexadecanamide | C31H52N6O9 | 详情 | 详情 |