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【结 构 式】 
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【分子编号】38018 【品名】(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate 【CA登记号】 |
【 分 子 式 】C21H27N5O8 【 分 子 量 】477.47428 【元素组成】C 52.83% H 5.7% N 14.67% O 26.81% |
合成路线1
该中间体在本合成路线中的序号：(X)The cyclization of the imidazolyl riboside (I) with [13C]-formic acid ethyl ester (II) by means of sodium ethoxide in refluxing ethanol gives labeled inosine (III), which is acetylated with Ac2O and pyridine yielding the triacetate (IV). The nitration of (IV) with ammonium nitrate and trifluoroacetic anhydride affords the 1-nitroinosine (V), which is rearranged with 15NH4Cl in acetonitrile/water to provide the doubly labeled inosine (VI). The reaction of (VI) with SOCl2 gives the chloropurine (VII), which is condensed with the dideuterated 2-aminocyclopentanol (rac-trans)-(VIII) (obtained by hydrogenation of the unsaturated analogue (rac-trans)-(IX)) by means of NaHCO3 in isopropanol providing a diastereomeric mixture (X). The deacetylation of (X) with tert-butylamine in methanol furnishes a mixture of the target compound along with its diastereomer, which is separated by preparative HPLC.
| 【1】 Wadsworth, A.H.; et al.; Synthesis of isotopically labelled versions of adenosine agonist GR79236. J Label Compd Radiopharm 2000, 43, 1, 11. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV),(VI) | 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 | |
| (I) | 37427 | 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carboxamide | C9H14N4O5 | 详情 | 详情 | |
| (II) | 16602 | ethyl formate | 109-94-4 | C3H6O2 | 详情 | 详情 |
| (II) | 45175 | ethyl formate | C3H6O2 | 详情 | 详情 | |
| (III) | 38013 | 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one | C10H12N4O5 | 详情 | 详情 | |
| (III) | 45176 | 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one | C10H12N4O5 | 详情 | 详情 | |
| (IV) | 45177 | (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 | |
| (V) | 38015 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H17N5O10 | 详情 | 详情 | |
| (V) | 45178 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H17N5O10 | 详情 | 详情 | |
| (VI) | 45179 | (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 | |
| (VII) | 38016 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H17ClN4O7 | 详情 | 详情 | |
| (VII) | 45180 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H17ClN4O7 | 详情 | 详情 | |
| (VIII) | 38010 | (1S,2S)-2-aminocyclopentanol | C5H11NO | 详情 | 详情 | |
| (VIII) | 45181 | (1S,2S)-2-aminocyclopentanol | C5H11NO | 详情 | 详情 | |
| (IX) | 38017 | (1S,2S)-2-amino-3-cyclopenten-1-ol | C5H9NO | 详情 | 详情 | |
| (X) | 38018 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C21H27N5O8 | 详情 | 详情 | |
| (X) | 45182 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C21H27N5O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The commercially available 8-[14C]-inosine (I) with Ac2O in hot pyridine gives the triacetate (II), which is treated with SOCl2 and DMF in dichloromethane yielding the chloropurine (III). The condensation of (III) with (1S-trans)-2-aminocyclopentanol by means of NaHCO3 in hot isopropanol affords the acetylated target compound (V), which is finally deacetylated with t-Bu-NH2 in methanol.
| 【1】 Wadsworth, A.H.; et al.; Synthesis of isotopically labelled versions of adenosine agonist GR79236. J Label Compd Radiopharm 2000, 43, 1, 11. |
| 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) | 38013 | 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one | C10H12N4O5 | 详情 | 详情 | |
| (I) | 63751 | 9-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one | 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 | |
| (II) | 63752 | 4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H18N4O8 | 详情 | 详情 | |
| (III) | 38015 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H17N5O10 | 详情 | 详情 | |
| (III) | 63753 | 4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H17ClN4O7 | 详情 | 详情 | |
| (IV) | 38017 | (1S,2S)-2-amino-3-cyclopenten-1-ol | C5H9NO | 详情 | 详情 | |
| (V) | 38018 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C21H27N5O8 | 详情 | 详情 | |
| (V) | 63754 | 4-(acetyloxy)-2-[(acetyloxy)methyl]-5-{6-[(2-hydroxycyclopentyl)amino]-9H-purin-9-yl}tetrahydro-3-furanyl acetate | C21H27N5O8 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VI)The condensation of the ribosyl chloropurine (I) with (rac-trans)-2-amino-3-cyclopentenol (II) by means of NaHCO3 in isopropanol gives a diastereomeric mixture of adenosine derivatives (III) + (IV) that is separated by HPLC. The desired isomer (III) is acetylated with Ac2O and pyridine yielding the tetraacetate (V), which is hydrogenated with tritium over Pt in THF to afford the tetraacetate (VI) of the target compound. Finally, (VI) is deacetylated by means of t-BuNH2 in methanol.
| 【1】 Wadsworth, A.H.; et al.; Synthesis of isotopically labelled versions of adenosine agonist GR79236. J Label Compd Radiopharm 2000, 43, 1, 11. |
| 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) | 18716 | 6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 2004-06-0 | C10H11ClN4O4 | 详情 | 详情 |
| (II) | 38017 | (1S,2S)-2-amino-3-cyclopenten-1-ol | C5H9NO | 详情 | 详情 | |
| (III) | 38019 | (2R,3R,4S,5R)-2-(6-[[(1S,5S)-5-hydroxy-2-cyclopenten-1-yl]amino]-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C15H19N5O5 | 详情 | 详情 | |
| (IV) | 38020 | (2R,3R,4S,5R)-2-(6-[[(1R,5R)-5-hydroxy-2-cyclopenten-1-yl]amino]-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C15H19N5O5 | 详情 | 详情 | |
| (V) | 38021 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,5S)-5-hydroxy-2-cyclopenten-1-yl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C21H25N5O8 | 详情 | 详情 | |
| (VI) | 38018 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C21H27N5O8 | 详情 | 详情 |