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【结 构 式】 
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【分子编号】62916 【品名】{(2S,3R)-5-hydroxy-3-[(4-methylbenzoyl)oxy]tetrahydro-2-furanyl}methyl 4-methylbenzoate 【CA登记号】 |
【 分 子 式 】C21H22O6 【 分 子 量 】370.40208 【元素组成】C 68.1% H 5.99% O 25.92% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The reaction of L-arabinose (I) with acetic anhydride and HBr gives tri-O-acetyl-b-L-arabinopyranosyl bromide (II), which is treated with Zn and Cu-Zn couple in aqueous AcOH to yield 3,4-di-O-acetyl-L-arabinal (III) (1). Reaction of compound (III) with HCl followed by treatment with refluxing methanol affords methyl 3,4-di-O-acetyl-2-deoxy-L-riboside (IV), which is deacetylated by means of NaOMe in methanol to provide methyl 2-deoxy-L-riboside (V). Reaction of riboside (V) with benzoic acid gives 2-deoxy-L-ribofuranose (VI), which, alternatively, can be obtained directly from diacetate (III) by treatment with aqueous HClO4 in AcOH/Ac2O. Reaction of ribofuranose (VI) with p-toluoyl chloride and methanol gives methyl 3,4-di-O-toluoyl-2-deoxy-L-riboside (VII), which is demethylated with HCl to yield 3,4-di-O-toluoyl-2-deoxy-L-ribose (VIII). Acylation of the ribose (VIII) with Ac2O and pyridine affords 1-O-acetyl-3,4-di-O-toluoyl-2-deoxy-L-ribose (IX), which is treated with HCl to provide the chloro-ribose (X). Condensation of compound (X) with thymine (XI) by means of HgCl2 and CdCO3 gives the acylated thymidine (XII), which is finally deacylated by treatment with NaOMe in methanol.
| 【1】 Smejkal, J.; Sorm, F.; Nucleic acids components and their analogues. LIII. Preparation of 1-2'-deoxy-beta-L-ribofuranosylthymine, "L-thymidine". Coll Czech Chem Commun 1964, 29, 11, 2809. |
| 【2】 Sorbera, L.A.; Castañer, J.; Castañer, R.M.; Bayes, M.; Telbivudine. Drugs Fut 2003, 28, 9, 870. |
| 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) | 17520 | (3R,4S,5S)tetrahydro-2H-pyran-2,3,4,5-tetrol; L-(+)-Arabinose | 7296-56-2 | C5H10O5 | 详情 | 详情 |
| (II) | 20353 | (2S,3R,4S,5S)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate | C11H15BrO7 | 详情 | 详情 | |
| (III) | 54162 | (3S,4R)-3-(acetyloxy)-3,4-dihydro-2H-pyran-4-yl acetate | n/a | C9H12O5 | 详情 | 详情 |
| (IV) | 62912 | (3S,4R)-4-(acetyloxy)-6-methoxytetrahydro-2H-pyran-3-yl acetate | C10H16O6 | 详情 | 详情 | |
| (V) | 62913 | (3S,4R)-6-methoxytetrahydro-2H-pyran-3,4-diol | C6H12O4 | 详情 | 详情 | |
| (VI) | 62914 | (4R,5S)-5-(hydroxymethyl)tetrahydro-2,4-furandiol | C5H10O4 | 详情 | 详情 | |
| (VII) | 62915 | {(2S,3R)-5-methoxy-3-[(4-methylbenzoyl)oxy]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C22H24O6 | 详情 | 详情 | |
| (VIII) | 62916 | {(2S,3R)-5-hydroxy-3-[(4-methylbenzoyl)oxy]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C21H22O6 | 详情 | 详情 | |
| (IX) | 62917 | {(2S,3R)-5-(acetyloxy)-3-[(4-methylbenzoyl)oxy]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C23H24O7 | 详情 | 详情 | |
| (X) | 37194 | (2R,3S)-5-Chloro-2-[[(4-methylbenzoyl)oxy]methyl]tetrahydro-3-furanyl 4-methylbenzoate | 4330-21-6 | C21H21ClO5 | 详情 | 详情 |
| (XI) | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |
| (XII) | 62918 | {(2S,3R,5S)-3-[(4-methylbenzoyl)oxy]-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C26H26N2O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)
| 【1】 Storer R. Moussa A. Wang JY. et al. 2005. Synthesis of β-L-2-deoxy-nucleosides from furanoses and pyranoses via a chloro-sugar and anhydro-l-furanosyl-nucleobase intennediatcs as potential antiviral and antineoplastic agents. W0 2005003374 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 66768 | (3S,5S)-3,4-dihydroxy-5-(hydroxymethyl)dihydrofuran-2(3H)-one | C5H8O5 | 详情 | 详情 | |
| (VI) | 66772 | 4-hydroxy-5-(hydroxymethyl)dihydrofuran-2(3H)-one | C5H8O4 | 详情 | 详情 | |
| （X） | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |
| (I) | 66767 | (3S,4R,5S)tetrahydro-2H-pyran-2,3,4,5-tetrol | C5H10O5 | 详情 | 详情 | |
| (III) | 66769 | 3-bromo-5-(bromomethyl)-4-hydroxydihydrofuran-2(3H)-one | C5H6Br2O3 | 详情 | 详情 | |
| (IV) | 66770 | 5-(bromomethyl)-4-hydroxydihydrofuran-2(3H)-one | C5H7BrO3 | 详情 | 详情 | |
| (V) | 66771 | potassium 3-hydroxy-3-(oxiran-2-yl)propanoate | C5H7KO4 | 详情 | 详情 | |
| (VII) | 66773 | C21H21O6 | 详情 | 详情 | ||
| (VIII) | 62916 | {(2S,3R)-5-hydroxy-3-[(4-methylbenzoyl)oxy]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C21H22O6 | 详情 | 详情 | |
| (IX) | 37194 | (2R,3S)-5-Chloro-2-[[(4-methylbenzoyl)oxy]methyl]tetrahydro-3-furanyl 4-methylbenzoate | 4330-21-6 | C21H21ClO5 | 详情 | 详情 |
| (XI) | 12238 | 5-Methyl-1,3-bis(trimethylsilyl)-2,4(1H,3H)-pyrimidinedione | 3444-09-5 | C11H22N2O2Si2 | 详情 | 详情 |
| (XII) | 62918 | {(2S,3R,5S)-3-[(4-methylbenzoyl)oxy]-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C26H26N2O7 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：（X）
| 【1】 Storer R. Moussa A. Wang JY. Et al. 2005. Synthesis of β-L-2-deoxy-nucleosides from furanoses and pyranoses via a chloro-sugar and anhydro-l-furanosyl-nucleobase intennediatcs as potential antiviral and antineoplastic agents. W0 2005003374 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| （X） | 62916 | {(2S,3R)-5-hydroxy-3-[(4-methylbenzoyl)oxy]tetrahydro-2-furanyl}methyl 4-methylbenzoate | C21H22O6 | 详情 | 详情 | |
| (I) | 66781 | 5-(1,2-dihydroxyethyl)-3,4-dihydroxydihydrofuran-2(3H)-one | C6H10O6 | 详情 | 详情 | |
| (II) | 66782 | 3-bromo-5-(2-bromo-1-hydroxyethyl)-4-hydroxydihydrofuran-2(3H)-one | C6H8Br2O4 | 详情 | 详情 | |
| (III) | 66783 | 2,6-dibromo-3,4,5-trihydroxyhexanehydrazide | C6H12Br2N2O4 | 详情 | 详情 | |
| (IV) | 66784 | 5-(2-bromo-1-hydroxyethyl)-4-hydroxydihydrofuran-2(3H)-one | C6H9BrO4 | 详情 | 详情 | |
| (V) | 66785 | potassium 3,4-dihydroxy-4-(oxiran-2-yl)butanoate | C6H9KO5 | 详情 | 详情 | |
| (VI) | 66786 | potassium 3-hydroxy-3-(3-(hydroxymethyl)oxiran-2-yl)propanoate | C6H9KO5 | 详情 | 详情 | |
| (VII) | 66787 | 5-(1,2-dihydroxyethyl)-4-hydroxydihydrofuran-2(3H)-one | C6H10O5 | 详情 | 详情 | |
| (VIII) | 66772 | 4-hydroxy-5-(hydroxymethyl)dihydrofuran-2(3H)-one | C5H8O4 | 详情 | 详情 | |
| (IX) | 66773 | C21H21O6 | 详情 | 详情 | ||
| (XI) | 66788 | 3,5-bis(benzyloxy)-2-((benzyloxy)methyl)tetrahydrofuran | C26H28O4 | 详情 | 详情 |