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【结 构 式】

【分子编号】68813

【品名】9-((2S,3S,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1-(2,4-dinitrophenyl)-1H-purin-6(9H)-one

【CA登记号】

【 分 子 式 】C16H14N6O9

【 分 子 量 】434.322

【元素组成】C 44.25% H 3.25% N 19.35% O 33.15%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VIII)

Acylation of inosine (I) with Ac2O in the presence of pyridine yields inosine triacetate (II), which is then protected as the N-MEM derivative (III) using chloromethyl methyl ether and DIEA in CH2Cl2. Deacetylation of compound (III) with NH3 in MeOH affords 1-MEMinosine (IV), which finally undergoes purine ring opening in refluxing NaOH .
In a related method, acadesine is obtained by MEM protection of inosine acetate (II) with chloromethyl methyl ether by means of NaH in dioxane, and subsequent purine ring hydrolysis with NaOH in refluxing EtOH .
Similarly, direct hydrolysis of unprotected inosine (I) with KOH in water at 130 °C produces a mixture of acadesine and 9-β-D-ribopyranosylhypoxanthine, from which acadesine can be isolated using column chromatography .
An alternative strategy is the hydrolysis of the imidazolecarbonitrile (V) with NaOH at 100 °C .
In a different approach, reaction of 2’,3’-O-isopropylideneinosine (VI) with 2,4-dinitrochlorobenzene (DNCB) by means of K2CO3 at 80 °C yields N1-(2,4-dinitrophenyl)-2’,3’-O-isopropylideneinosine (VII), which is then O-deprotected with HCOOH in H2O to give 1-(2,4-dinitrophenyl) inosine (VIII). Regioselective attachment of the triol (VIII) to MMTCl resin in the presence of DMAP in pyridine provides the resin-bound compound (IX), which is then submitted to purine ring hydrolysis with EDA in DMF, and subsequent deprotection of the obtained intermediate with TFA in CH2Cl2 .

1 Kohyama, N., Yamamoto, Y. A facile synthesis of AICAR from inosine. Synthesis 2001, 17: 2639-42.
2 Shaw, E. A chemical preparation of 5-amino-4-imidazolecarboxamide ribotide. J Am Chem Soc 1961, 83(23): 4770-2.
3 Suzuki, Y. Action of alkali on inosine - Formation of 5-amino-1-beta-Dribofuranosyl-4-imidazolecarboxamide and 9-beta-D-ribopyranosyl hypoxanthine. Bull Chem Soc Jpn 1974, 47(4): 898-903.
4 Ferris, J.P., Devadas, B., Huang, C.H., Ren, W.Y. Novel synthesis of 5-amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide and 5-amino-1-(beta-D-ribopyranosyl)imidazole-4-carboxamide. J Org Chem 1985, 50(6): 747-54.
5 Oliviero, G., Amato, J., Borbone, N., D’Errico, S., Piccialli, G., Mayol, L. Synthesis of N-1 and ribose modified inosine analogues on solid support. Tetrahedron Lett 2007, 48(3): 397-400.
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) 12795 (2R,3S,4R,5R)-2-(Hydroxymethyl)-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-3,4-furandiol; Inosine 58-63-9 C10H12N4O5 详情 详情
(II) 38014 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate C16H18N4O8 详情 详情
(III) 68809 (2R,3R,4S,5R)-2-(acetoxymethyl)-5-(1-((2-methoxyethoxy)methyl)-6-oxo-1H-purin-9(6H)-yl)tetrahydrofuran-3,4-diyl diacetate C20H26N4O10 详情 详情
(IV) 68810 9-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1-((2-methoxyethoxy)methyl)-1H-purin-6(9H)-one C14H20N4O7 详情 详情
(V) 37430 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carbonitrile C9H12N4O4 详情 详情
(VI) 68811 9-((3aS,4S,6S,6aS)-6- (hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d] [1,3]dioxol-4-yl)-1H-purin-6(9H)-one C13H16N4O5 详情 详情
(VII) 68812 1-(2,4-dinitrophenyl)-9-((3aS,4S,6S,6aS)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-1H-purin-6(9H)-one C19H18N6O9 详情 详情
(VIII) 68813 9-((2S,3S,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1-(2,4-dinitrophenyl)-1H-purin-6(9H)-one C16H14N6O9 详情 详情
(IX) 68814   C16H13N6O9 详情 详情
Extended Information