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【结 构 式】 
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【分子编号】12161 【品名】Thymidine; 1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione 【CA登记号】50-89-5 |
【 分 子 式 】C10H14N2O5 【 分 子 量 】242.23164 【元素组成】C 49.58% H 5.83% N 11.56% O 33.03% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of aniline (I) with diethyl ethoxymethylenemalonate (II) by heating at 90 C gives diethyl anilinomethylenemalonate (III), which is cyclized to ethyl 4-hydroxyquinoline-3-carboxylate (IV) by heating at 240 C in diphenyl ether-biphenyl. The reaction of (IV) with hot POCl3 affords ethyl 4-chloro-quinoline-3-carboxylate (V), which is finally cyclized with phenylhydrazine (VI) by heating at 105 C in xylene. (VI) is prepared in the usual way starting from aniline (I) by diazotation with NaNO2-HCl to phenyldiazonium chloride (VII), and reduction with SnCl2-HCl.
| 【1】 Urbanski, J.A.; Chua, J.; Tomson, A.J.; Horwitz, J.P.; Nucleosides. I. 5'-Amino-5'-deoxyuridine and 5'-amino-5'-deoxythymidine. J Org Chem 1962, 27, 3045-48. |
| 【2】 Prusoff, W.H.; Lin, T.S.; Synthesis and biological activity of several amino analogues of thymidine. J Med Chem 1978, 21, 1, 109-112. |
| 【3】 Blancafort, P.; Hopkins, S.J.; Castaner, J.; Serradell, M.N.; AdThd. Drugs Fut 1983, 8, 3, 179. |
| 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) | 35959 | [(2R,3S,5R)-3-hydroxy-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl 4-methylbenzenesulfonate | C17H20N2O7S | 详情 | 详情 | |
| (III) | 35960 | 1-[(2R,4S,5R)-5-(azidomethyl)-4-hydroxytetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C10H13N5O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)2) The anhydrization of thymidine (VI) with 2-chloro-1,2-difluorotriethylamine in hot DMF gives 2,3'-anhydrothymidine (VII), which is then treated with lithium azide and NH4Cl in hot DMF.
| 【1】 Glinski, R.P.; et al.; Nucleotide synthesis. IV. Phosphorylated 3'-amino-3'-deoxythymidine and 5'-amino-5'-deoxythymidine and derivatives. J Org Chem 1973, 38, 25, 4299. |
| 【2】 Castaner, J.; Prous, J.; BW-A 509 U. Drugs Fut 1986, 11, 12, 1017. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 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 |
| (VII) | 24471 | (1R,9S,10R)-10-(hydroxymethyl)-4-methyl-8,11-dioxa-2,6-diazatricyclo[7.2.1.0(2,7)]dodeca-3,6-dien-5-one; 2,3'-Anhydrothymidine; 2,3'-2,3'-Anhydrothimidine | C10H12N2O4 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Alovudine can be obtained by several related ways: 1) The acylation of thymidine (I) with 4-chlorobenzoylchloride (II) in pyridine gives 5'-O-(4-chlorobenzoyl)thymidine (IX), which is then treated with diethylamino sulfur trifluoride in methylene chloride at -79 C, and finally with NaHCO3 in refluxing methanol. 2) By reaction of 2,3'-anhydro-1-(2'-deoxy-beta-D-xylofuranosyl)thymine (III) with AlF3 and 1% HF in anhydrous dioxan at 150-7 C. 3) By reaction of (III) with KHF2 or NH4F in diethylene glycol at 190C, or in ethanol at 150 C. 4) The reaction of 2,3'-anhydro-5'-O-(methylsufonyl)-1-(2'-deoxy-beta-D-xylofuranosyl) thymine (IV) with AlF3 and HF as before gives 3'-deoxy-3'-fluoro-5'-O-(methylsulfonyl)thymidine (V), which is then treated with NaOH in refluxing ethanol. 5) By reaction of 5'-O-(triphenylmethyl)thymidine (VI) with diethylamino sulfur trifluoride in THF, and then with aqueous, NaHCO3. 6) By reaction of 3'-O-(methylsulfonyl)thymidine (VII) with KHF2 or NH4F in diethylene glycol at 190 C. 7) By reaction of 2,3'-anhydro-5'-O-(triphenylmethyl)-1-(2'-deoxy-beta-D-xylofuranosyl) thymine (VIII) with 4-6% HF in anhydrous dioxan at 90 C.
| 【1】 Selway, J.W.T.; Beacham III, L.M.; Daluge, S.M.; Tuttle, J.V.; Krenitsky, T.A. (Glaxo Wellcome plc); 2,3-Dideoxy-3'-fluorothymidine and related cpds. for the treatment of adenovirus infections. AU 8821429; EP 0305117; EP 0479336; JP 1989068325; US 5070078 . |
| 【2】 Etzold, G.; Hintsche, R.; Langen, P. (Akademie der Wissenschaften der DDR); Cytostatically-active 2',3'-didesoxy-3'-fluoropyrimidine nucleosides. GB 1189973 . |
| 【3】 Castaner, J.; Hoshi, A.; Alovudine. Drugs Fut 1994, 19, 3, 221. |
| 【4】 Baba, M.; De Clercq, E.; Pauwels, R.; Herdewijn, P.; Balzarini, J.; Vanderhaeghe, H.; Broder, S.; 3'-Substituted 2',3'-dideoxynucleoside analogues as potential anti-HIV (HTLV-III/LAV) agents. J Med Chem 1987, 30, 8, 1270-8. |
| 【5】 Kowollik, G.; Etzold, G.; Hintsche, R.; Langen, P.; Synthesis and reactivity of 3'-fluoro and 3'-chloro-3'-desoxy-thymidine. Tetrahedron 1971, 27, 2463-72. |
| 【6】 Langen, P.; Von Janta-Lipinski, M.; Gaertner, K.; Etzold, G.; Von Kowollik, G.; A novel access to 1-(2,3-didesoxy-3-fluoro-beta-D-ribofuranosyl)-pyrimidines. J Prakt Chem 1973, 315, 5, 895-900. |
| 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) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |
| (III) | 12163 | (1R,9R,10R)-10-(Hydroxymethyl)-4-methyl-8,11-dioxa-2,6-diazatricyclo[7.2.1.0(2,7)]dodeca-3,6-dien-5-one | C10H12N2O4 | 详情 | 详情 | |
| (IV) | 12164 | [(1R,9R,10R)-4-methyl-5-oxo-8,11-dioxa-2,6-diazatricyclo[7.2.1.0(2,7)]dodeca-3,6-dien-10-yl]methyl methanesulfonate | C11H14N2O6S | 详情 | 详情 | |
| (V) | 12165 | [(2R,3S,5R)-3-fluoro-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl methanesulfonate | C11H15FN2O6S | 详情 | 详情 | |
| (VI) | 12166 | 1-[(2R,4S,5R)-4-Hydroxy-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C29H28N2O5 | 详情 | 详情 | |
| (VII) | 12167 | (2R,3S,5R)-2-(hydroxymethyl)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-3-furanyl methanesulfonate | C11H16N2O7S | 详情 | 详情 | |
| (VIII) | 12168 | (1R,9R,10R)-4-Methyl-10-[(trityloxy)methyl]-8,11-dioxa-2,6-diazatricyclo[7.2.1.0(2,7)]dodeca-3,6-dien-5-one | C29H26N2O4 | 详情 | 详情 | |
| (IX) | 63321 | methyl 4-[2-(tert-butylamino)acetyl]-7-hydroxy-1H-indole-2-carboxylate | C16H20N2O4 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)1) The first method ever reported involves the mesylation of thymidine (I) to give dimesylate (II), which is treated with sodium hydroxide in ethanol to yield oxetane (III). Finally, (III) is converted to stavudine by means of potassium tert-butoxide in DMSO. This process has been modified in order to obtain large quantities or to obtain [2-14C]-stavudine starting from [2-14C]-thymidine. 2) A second closely related method, but using a different protecting group strategy, involves tritylation of the primary hydroxyl group of thymidine to give (IVa), which is then mesylated to give (Va). Elimination with TBAF/THF or t-BuOK/DMSO yields compound (VI), which is finally deprotected with acetic acid. 3) A third synthesis starting from thymidine involves its protection with monomethoxytrityl chloride or picolyl chloride to give (IVb) or (IVc), respectively, which are mesylated to give (Vb) or (Vc). These are treated with phenyl diselenide and lithium aluminum hydride in tetrahydrofuran to yield compounds (VIIb) or (VIIc), which are treated with m-chloroperbenzoic acid in dichloromethane to afford (VIIIb) or (VIIIc). Finally, (VIIIb) is deprotected with methylamine in water and (VIIIc) is deprotected with acetic acid.
| 【1】 Martin, J.C.; Hitchcock, M.J.M.; Starrett, J.E. Jr.; Ghazzouli, I.; Mansuri, M.M.; Ho, H.-T.; Sommadossi, J.-P.; Brankovan, V.; Synthesis, anti-HIV activity, and biological properties of 2',3'-didehydro-2',3'-dideoxythymidine (D4T). Nucleosides Nucleotides 1989, 32, 461-6. |
| 【2】 Starret, J.E. Jr.; Mansuri, M.M.; Martin, J.C.; Fuller, C.E.; Howell, H.G. (Bristol-Myers Squibb Co.); Production of 2',3'-dideoxy-2',3'-didehydronucleosides. EP 0334368 . |
| 【3】 Lin, T.-S.; Prusoff, W.H. (Yale University); Pharmaceutical compsn. comprising 3'-deoxythymidin-2'-ene (3'-deoxy-2',3'-didehydrothymidine) in treating patients infected with retrovirus. EP 0273277 . |
| 【4】 Mansuri, M.M.; Ghazzouli, I.; Starrett, J.E. Jr.; Hitchcock, M.J.; Sterzycki, R.Z.; Brankovan, V.; Lin, T.S.; August, E.M.; Prusoff, W.H.; Sommadossi, J.P.; et al.; 1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine. A highly potent and selective anti-HIV agent. J Med Chem 1989, 32, 2, 461-6. |
| 【5】 Lin, T.-S.; Gao, Y.-S.; August, E.M.; Prusoff, W.H.; Qian, H.-Y.; Synthesis of [2-14C]3'-deoxythymidin-2'-ene (d4T) and [5-125I]3'-azido-2',3'-dideoxy-5-iodouridine: Potent inhibitors of human immunodeficiency virus (HIV-1). J Label Compd Radiopharm 1989, 27, 6, 669-74. |
| 【6】 Da Rooge, M.A.; Noel, M.; Horwitz, J.P.; Chua, J.; Klundt, I.L.; Nucleosides. IX. The formation of 2',3'-unsaturated pyrimidine nucleosides via a novel beta-elimination reaction. J Org Chem 1966, 31, 205-11. |
| 【7】 Chattopadhyaya, J.; Agback, P.; Vial, J.M.; A new synthesis of 1-(2,3-dideoxy-beta-D-glycero-pent-2-enofuranosyl)-thymine. A highly potent and selective anti-HIV agent. Nucleosides Nucleotides 1990, 9, 2, 245-58. |
| 【8】 Baba, M.; De Clercq, E.; Pauwels, R.; Herdewijn, P.; Balzarini, J.; Vanderhaeghe, H.; Broder, S.; 3'-Substituted 2',3'-dideoxynucleoside analogues as potential anti-HIV (HTLV-III/LAV) agents. J Med Chem 1987, 30, 8, 1270-8. |
| 【9】 Robinson, C.; Castaner, J.; Stavudine. Drugs Fut 1994, 19, 10, 925. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IVa) | 12166 | 1-[(2R,4S,5R)-4-Hydroxy-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C29H28N2O5 | 详情 | 详情 | |
| (IVb) | 12194 | 1-((2R,4S,5R)-4-Hydroxy-5-[[(4-methoxyphenyl)(diphenyl)methoxy]methyl]tetrahydro-2-furanyl)-5-methyl-2,4(1H,3H)-pyrimidinedione | C30H30N2O6 | 详情 | 详情 | |
| (IVc) | 12195 | [(2R,3S,5R)-3-hydroxy-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl 2-pyridinecarboxylate | C16H17N3O6 | 详情 | 详情 | |
| (Va) | 12196 | (2R,3S,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-[(trityloxy)methyl]tetrahydro-3-furanyl methanesulfonate | C30H30N2O7S | 详情 | 详情 | |
| (Vb) | 12197 | (2R,3S,5R)-2-[[(4-methoxyphenyl)(diphenyl)methoxy]methyl]-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-3-furanyl methanesulfonate | C31H32N2O8S | 详情 | 详情 | |
| (Vc) | 12198 | [(2R,3S,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-3-[(methylsulfonyl)oxy]tetrahydro-2-furanyl]methyl 2-pyridinecarboxylate | C17H19N3O8S | 详情 | 详情 | |
| (VIa) | 12199 | 5-Methyl-1-[(2R,5S)-5-[(trityloxy)methyl]-2,5-dihydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione | C29H26N2O4 | 详情 | 详情 | |
| (VIIb) | 12200 | 1-[(2R,4R,5R)-5-[[(4-Methoxyphenyl)(diphenyl)methoxy]methyl]-4-(phenylselanyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C36H34N2O5Se | 详情 | 详情 | |
| (VIIc) | 12201 | [(2R,3R,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-3-(phenylselanyl)tetrahydro-2-furanyl]methyl 2-pyridinecarboxylate | C22H21N3O5Se | 详情 | 详情 | |
| (VIIIb) | 12202 | 1-((2R,5S)-5-[[(4-Methoxyphenyl)(diphenyl)methoxy]methyl]-2,5-dihydro-2-furanyl)-5-methyl-2,4(1H,3H)-pyrimidinedione | C30H28N2O5 | 详情 | 详情 | |
| (VIIIc) | 12203 | 1-[(2R,5S)-5-(Methoxymethyl)-2,5-dihydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C11H14N2O4 | 详情 | 详情 | |
| (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) | 12191 | ((2R,3S,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-3-[[methyl(methylene)oxo-lambda(6)-sulfanyl]oxy]tetrahydro-2-furanyl)methyl methanesulfonate | C13H20N2O8S2 | 详情 | 详情 | |
| (III) | 12192 | 1-[(1R,3R,5R)-2,6-Dioxabicyclo[3.2.0]hept-3-yl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C10H12N2O4 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VI)A new synthesis of stavudine has been reported: The condensation of thymine (I) with methyl 2-deoxyribofuranoside (II) by means of N-bromosuccinimide (NBS) followed by protection with TBDPS-Cl gives the intermediate (III), which is cyclized by means of trimethylsilyl triflate (TMS-OTf), yielding the cyclothymidine derivative (IV). The deprotection of (IV) with tetrabutylammonium fluoride affords the unprotected compound (V), which is finally treated successively with triflate anhydride, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and Zn/acetic acid. The unprotected intermediate compound (V) can also be obtained by cyclization of thymidine (VI) by means of NBS in DMF, catalyzed by trifluoroacetic acid.
| 【1】 Lowe, R.F.; Lipshutz, B.H.; Stevens, K.L.; A novel route to the anti-HIV nucleoside d4T. Tetrahedron Lett 1995, 36, 16, 2711. |
| 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) | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |
| (II) | 12241 | (2R,3S)-2-(Hydroxymethyl)-5-methoxytetrahydro-3-furanol | C6H12O4 | 详情 | 详情 | |
| (III) | 12242 | 5-Bromo-6-[((2R,3S)-3-[[tert-butyl(diphenyl)silyl]oxy]-5-methoxytetrahydro-2-furanyl)methoxy]-5-methyldihydro-2,4(1H,3H)-pyrimidinedione | C27H35BrN2O6Si | 详情 | 详情 | |
| (IV) | 12243 | (1R,10R,11S)-6-Bromo-11-[[tert-butyl(diphenyl)silyl]oxy]-6-methyl-8,13-dioxa-2,4-diazatricyclo[8.2.1.0(2,7)]tridecane-3,5-dione | C26H31BrN2O5Si | 详情 | 详情 | |
| (V) | 12244 | (1R,10R,11S)-6-Bromo-11-hydroxy-6-methyl-8,13-dioxa-2,4-diazatricyclo[8.2.1.0(2,7)]tridecane-3,5-dione | C10H13BrN2O5 | 详情 | 详情 | |
| (VI) | 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 |
合成路线6
该中间体在本合成路线中的序号：(I)The benzoylation of thymidine (I) with benzoyl chloride, PPh3 and DIAD in THF gives the 5'-O-benzoylthymidine (II), which is converted into the anhydro compound (III) by reaction with PPh3 and DIAD in DMF. The reaction of (III) with PhSeH in refluxing DMF affords the phenylselenium derivative (IV), which is treated with H2O2 and HOAc in THF to provide the benzoylated anhydrothymidine (V). Finally this compound is debenzoylated by means of NaOMe in methanol.
| 【1】 Becouarn, S.; Czernecki, S.; Valery, J.-M.; Efficient transformation of thymidine into 2',3'-didehydro-2',3'-dideoxy-thymidine (D4T) involving opening of a 2,3'-anhydro derivative by phenylselenol. Nucleosides Nucleotides 1995, 14, 6, 1227. |
| 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) | 41902 | [(2R,3S,5R)-3-hydroxy-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl benzoate | C17H18N2O6 | 详情 | 详情 | |
| (III) | 41903 | [(1R,9S,10R)-4-methyl-5-oxo-8,11-dioxa-2,6-diazatricyclo[7.2.1.0(2,7)]dodeca-3,6-dien-10-yl]methyl benzoate | C17H16N2O5 | 详情 | 详情 | |
| (IV) | 41904 | [(2R,3S,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-3-(phenylselanyl)tetrahydro-2-furanyl]methyl benzoate | C23H22N2O5Se | 详情 | 详情 | |
| (V) | 12257 | 2,4,5-Trifluoro-3-methoxybenzamide | C8H6F3NO2 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(I)The reaction of 3'-deoxythymidine (I) with MsCl and TEA in acetone gives the mesylate (II), which is treated with aq. NaOH at 45-50 C to yield the anhydro compound (III). Finally, this compound is treated with KOH in refluxing tert-butanol to afford the target Stavudine.
| 【1】 Paramashivappa, R.; et al.; Simple and efficient method for the synthesis of 2',3'-didehydro-3'-deoxythymidine (d4T). Tetrahedron Lett 2003, 44, 5, 1003. |
| 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) | 62192 | {(2R,3S,5R)-3-hydroxy-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl methanesulfonate | C11H16N2O7S | 详情 | 详情 | |
| (III) | 12192 | 1-[(1R,3R,5R)-2,6-Dioxabicyclo[3.2.0]hept-3-yl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C10H12N2O4 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(I)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 |