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【结 构 式】 
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【分子编号】25323 【品名】1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione 【CA登记号】 |
【 分 子 式 】C10H12N2O4 【 分 子 量 】224.21636 【元素组成】C 53.57% H 5.39% N 12.49% O 28.54% |
合成路线1
该中间体在本合成路线中的序号：(II)The dehydration of thymidine (I) by known methods (J Med Chem 1989, 32: 461) gives 2,3-anhydrothymidine (II), which is then esterifired with the phosphoryl chloride (III) by means of 1-methylimidazole in THF.
| 【1】 Vig, R.; Venkatachalam, T.K.; Uckun, F.M.; D4T-5'-[p-Bromophenyl methoxyalaninyl phosphate] as a potent and non-toxic anti-human immunodeficiency virus agent. Antivir Chem Chemother 1998, 9, 5, 445. |
| 【2】 Venkatachalam, T.K.; Tai, H.-L.; Vig, R.; Chen, C.-L.; Jan, S.-T.; Uckun, F.M.; Enhancing effects of a mono-bromo substitution at the para position of the phenyl moiety on the metabolism and anti-HIV activity of d4T-phenyl methoxyalaninyl phosphate derivatives. Bioorg Med Chem Lett 1998, 8, 22, 3121. |
| 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) | 12161 | Thymidine; 1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | 50-89-5 | C10H14N2O5 | 详情 | 详情 |
| (II) | 25323 | 1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C10H12N2O4 | 详情 | 详情 | |
| (III) | 25316 | methyl 2-[[(4-bromophenoxy)(chloro)phosphoryl]amino]propanoate | C10H12BrClNO4P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Title phosphoramidate was obtained by condensation of phenyl [(2-naphthylmethoxy)alanino]phosphorochloridate (I) with 2',3'-dideoxy-2',3'-didehydrothymidine (II) in the presence of N-methylmorpholine in THF at r.t.
| 【1】 McGuigan, C.; Sutton, P.W.; Cahard, D.; Turner, K.; O'Leary, G.; Wang, Y.; Gumbleton, M.; De Clercq, E.; Balzarini, J.; Synthesis, anti-human immunodeficiency virus activity and esterase lability of some novel carboxylic ester-modified phosphoramidate derivatives of stavudine (d4T). Antivir Chem Chemother 1998, 9, 6, 473. |
合成路线3
该中间体在本合成路线中的序号：(II)Title phosphoramidate was obtained by condensation of phenyl (phenoxyalanino)phosphorochloridate (I) with 2',3'-dideoxy-2',3'-didehydrothymidine (II) in the presence of N-methylmorpholine in THF at r.t.
| 【1】 McGuigan, C.; Sutton, P.W.; Cahard, D.; Turner, K.; O'Leary, G.; Wang, Y.; Gumbleton, M.; De Clercq, E.; Balzarini, J.; Synthesis, anti-human immunodeficiency virus activity and esterase lability of some novel carboxylic ester-modified phosphoramidate derivatives of stavudine (d4T). Antivir Chem Chemother 1998, 9, 6, 473. |
合成路线4
该中间体在本合成路线中的序号：(II)Title phosphoramidate was obtained by condensation of phenyl (benzyloxyalanino)phosphorochloridate (I) with 2',3'-dideoxy-2',3'-didehydrothymidine (II) in the presence of N-methylmorpholine in THF at r.t.
| 【1】 Balzarini, J.; De Clercq, E.; Sheeka, H.M.; Cahard, D.; McGuigan, C.; Phosphoramidate derivatives of d4T with improved anti-HIV efficacy retain full activity in thymidine kinase-deficient cells. Bioorg Med Chem Lett 1996, 6, 10, 1183. |
| 【2】 McGuigan, C.; Sutton, P.W.; Cahard, D.; Turner, K.; O'Leary, G.; Wang, Y.; Gumbleton, M.; De Clercq, E.; Balzarini, J.; Synthesis, anti-human immunodeficiency virus activity and esterase lability of some novel carboxylic ester-modified phosphoramidate derivatives of stavudine (d4T). Antivir Chem Chemother 1998, 9, 6, 473. |
合成路线5
该中间体在本合成路线中的序号：(II)Title phosphoramidate was obtained by condensation of phenyl [(1-naphthylmethoxy)alanino]phosphorochloridate (I) with 2',3'-dideoxy-2',3'-didehydrothymidine (II) in the presence of N-methylmorpholine in THF at r.t.
| 【1】 McGuigan, C.; Sutton, P.W.; Cahard, D.; Turner, K.; O'Leary, G.; Wang, Y.; Gumbleton, M.; De Clercq, E.; Balzarini, J.; Synthesis, anti-human immunodeficiency virus activity and esterase lability of some novel carboxylic ester-modified phosphoramidate derivatives of stavudine (d4T). Antivir Chem Chemother 1998, 9, 6, 473. |