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【结 构 式】

【分子编号】30920

【品名】(2S,3R,4S,5S)-2-(acetoxy)-4-(benzyloxy)-5-[(benzyloxy)methyl]-5-methyltetrahydro-3-furanyl acetate

【CA登记号】

【 分 子 式 】C24H28O7

【 分 子 量 】428.48212

【元素组成】C 67.28% H 6.59% O 26.14%

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:(V)

The benzylation of 4-C-(hydroxymethyl)-1,2-isopropylidene-alpha-D-ribofuranose (I) with benzyl bromide and NaH in DMF gives the 3,5-di-O-benzyl derivative (II), which is treated with I2, imidazole and triphenylphosphine in refluxing toluene/acetonitrile yielding the iodomethyl derivative (III). The deiodination of (III) with tributyltin hydride and AIBN in hot toluene affords the 4-C-methyl compound (IV), which is treated with acetic anhydride and H2SO4 in acetic acid to give the 1,2-di-O-acetyl derivative (V). The condensation of (V) with uracil (VI) by means of TMS-OTf yields the uridine derivative (VII), which is deprotected first by deacetylation with ammonia and then by debenzylation with H2 over Pd/C affording the 4'-C-methyl-uridine (VIII). The reaction of (VIII) with acetyl bromide in refluxing acetonitrile gives the acetylated 2'-bromo derivative (IX), which is debrominated with tributyltin hydride and AIBN in hot toluene yielding 3',5'-O-diacetyl-2'-deoxy-4'-C-methyl-uridine (X). The iodination of (X) with I2 and ceric ammonium nitrate (CAN) affords the 5-iodo derivative (XI), which is condensed with methyl acrylate by means of Pd(OAc)2 and triphenylphosphine in dioxane giving the methoxycarbonylvinyl derivative (XII). The hydrolysis of (XII) with NaOH in methanol yields 5-(2(E)-carboxyvinyl)-2'-deoxy-4'-C-methyl-uridine (XIII), which is finally submitted to a decarboxylative bromination with N-bromosuccinimide ans KHCO3 in DMF.

1 Waga, T.; et al.; Synthesis of 4'-C-methylnucleosides. Biosci Biotech Biochem 1993, 57, 9, 1433-38.
2 Waga, T.; et al.; Synthesis and biological evaluation of 4'-C-methylnucleosides. Nucleosides Nucleotides 1996, 15, 1-3, 287-304.
3 Machida, H.; Kitano, K.; Miura, S.; Synthesis of novel 4'-C-methyl-pyrimidine nucleosides and their biological activities. Bioorg Med Chem Lett 1999, 9, 6, 827.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
12912 1-(Bromomethyl)benzene; Alpha-bromotoluene 100-39-0 C7H7Br 详情 详情
14156 methyl acrylate 96-33-3 C4H6O2 详情 详情
(I) 30916 [(3aR,6S,6aR)-6-(benzyloxy)-5-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methanol C16H22O6 详情 详情
(II) 30917 [(3aR,5S,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methanol C23H28O6 详情 详情
(III) 30918 (3aR,5S,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-5-(iodomethyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole; [(3aR,5S,6S,6aR)-6-(benzyloxy)-5-(iodomethyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether C23H27IO5 详情 详情
(IV) 30919 (3aR,5S,6S,6aR)-5-[(benzyloxy)methyl]-2,2,5-trimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl benzyl ether; (3aR,5S,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-2,2,5-trimethyltetrahydrofuro[2,3-d][1,3]dioxole C23H28O5 详情 详情
(V) 30920 (2S,3R,4S,5S)-2-(acetoxy)-4-(benzyloxy)-5-[(benzyloxy)methyl]-5-methyltetrahydro-3-furanyl acetate C24H28O7 详情 详情
(VI) 30921 2,4(1H,3H)-pyrimidinedione; Uracil 66-22-8 C4H4N2O2 详情 详情
(VII) 30922 (2R,3R,4S,5S)-4-(benzyloxy)-5-[(benzyloxy)methyl]-2-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-5-methyltetrahydro-3-furanyl acetate C26H28N2O7 详情 详情
(VIII) 30923 1-[(2R,3R,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)-5-methyltetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione C10H14N2O6 详情 详情
(IX) 30924 [(2S,3R,4R,5R)-3-(acetoxy)-4-bromo-5-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-methyltetrahydro-2-furanyl]methyl acetate C14H17BrN2O7 详情 详情
(X) 30925 [(2S,3S,5R)-3-(acetoxy)-5-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-methyltetrahydro-2-furanyl]methyl acetate C14H18N2O7 详情 详情
(XI) 30926 [(2S,3S,5R)-3-(acetoxy)-5-[5-iodo-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-methyltetrahydro-2-furanyl]methyl acetate C14H17IN2O7 详情 详情
(XII) 30927 methyl (E)-3-(1-[(2R,4S,5S)-4-(acetoxy)-5-[(acetoxy)methyl]-5-methyltetrahydro-2-furanyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)-2-propenoate C18H22N2O9 详情 详情
(XIII) 30928 (E)-3-[1-[(2R,4S,5S)-4-hydroxy-5-(hydroxymethyl)-5-methyltetrahydro-2-furanyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenoic acid C13H16N2O7 详情 详情
Extended Information