4'-MethylBVDU

合成路线: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.

参考文献标题:Synthesis of 4'-C-methylnucleosides
文献作者:Waga,T.; et al.
参考来源:Biosci Biotech Biochem 1993,57(9),1433-38


合成路线: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.
参考文献标题:Synthesis and biological evaluation of 4'-C-methylnucleosides
文献作者:Waga,T.; et al.
参考来源:Nucleosides Nucleotides 1996,15(1-3),287-304