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【结 构 式】 
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【分子编号】20353 【品名】(2S,3R,4S,5S)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate 【CA登记号】 |
【 分 子 式 】C11H15BrO7 【 分 子 量 】339.1399 【元素组成】C 38.96% H 4.46% Br 23.56% O 33.02% |
合成路线1
该中间体在本合成路线中的序号：(II)The condensation of 9-acetoxyellipticine (I) with 2,3,4-tri-O-acetyl-beta-L-arabinopyranosyl bromide (II) by means of CdCO3 in refluxing nitromethane gives the corresponding tetraacetoxy derivative (III), which is then deprotected by treatment with dry ammonia in methanol.
| 【1】 Honda, T.; Nakanishi, T. (Suntory Ltd.); Ellipticine derivs.. AU 8545252; EP 0173462; JP 1986037799; JP 1987022794; JP 1987022795; JP 1987030795; US 4698423 . |
| 【2】 Hoshi, A.; Prous, J.; Castaner, J.; ELLIPRAVIN. Drugs Fut 1989, 14, 2, 116. |
| 【3】 Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.; Yoshida, T.; Noguchi, T.; Synthesis and antitumor activity of quaternary ellipticine glycosides, a series of novel and highly active antitumor agents. J Med Chem 1988, 31, 7, 1295-305. |
| 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) | 20352 | 5,11-dimethyl-6H-pyrido[4,3-b]carbazol-9-yl acetate | C19H16N2O2 | 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) | 20354 | 9-(acetoxy)-5,11-dimethyl-2-[(2R,3R,4S,5S)-3,4,5-tris(acetoxy)tetrahydro-2H-pyran-2-yl]-6H-pyrido[4,3-b]carbazol-2-ium bromide | C30H31BrN2O9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)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3
该中间体在本合成路线中的序号：(III)
| 【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） | 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 | |
| (I) | 17520 | (3R,4S,5S)tetrahydro-2H-pyran-2,3,4,5-tetrol; L-(+)-Arabinose | 7296-56-2 | C5H10O5 | 详情 | 详情 |
| (II) | 66779 | tetrahydro-2H-pyran-2,3,4,5-tetrayl tetraacetate | C13H18O9 | 详情 | 详情 | |
| (III) | 20353 | (2S,3R,4S,5S)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate | C11H15BrO7 | 详情 | 详情 | |
| (IV) | 54162 | (3S,4R)-3-(acetyloxy)-3,4-dihydro-2H-pyran-4-yl acetate | n/a | C9H12O5 | 详情 | 详情 |
| (V) | 66780 | 3,4-dihydro-2H-pyran-3,4-diol | C5H8O3 | 详情 | 详情 | |
| (VI) | 12241 | (2R,3S)-2-(Hydroxymethyl)-5-methoxytetrahydro-3-furanol | C6H12O4 | 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) | 37194 | (2R,3S)-5-Chloro-2-[[(4-methylbenzoyl)oxy]methyl]tetrahydro-3-furanyl 4-methylbenzoate | 4330-21-6 | C21H21ClO5 | 详情 | 详情 |
| (IX) | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |