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【结 构 式】 
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【分子编号】48936 【品名】D-Arabinose tetraacetate 【CA登记号】 |
【 分 子 式 】C13H18O9 【 分 子 量 】318.28052 【元素组成】C 49.06% H 5.7% O 45.24% |
合成路线1
该中间体在本合成路线中的序号：(II)A new synthesis of clevudine has been described: Peracetylation of L-arabinose (I) with acetic anhydride and pyridine provides acetylated arabinose (II), which is then brominated by means of HBr in AcOH/Ac2O to furnish the bromo-sugar (III). Treatment of the sugar (III) with Zn dust, CuSO4 and NaOAc in AcOH/H2O, followed by chromatographic separation, gives L-arabinal (IV), which is then converted to the fluoro derivative (V) by reaction with Selectfluor?(F-TEDA-BF4) in refluxing nitromethane/H2O. Deacetylation of compound (V) with NaOMe in MeOH yields compound (VI), which is then converted into the methyl furanoside (VII) by treatment with H2SO4 in MeOH. Benzoylation of the furanoside (VII) with benzoyl chloride in pyridine affords a mixture of isomers, from which (VIII) is separated by chromatography and then brominated with HBr/AcOH in CH2Cl2 to provide the bromo-sugar (IX). Condensation of the sugar (IX) with the silylated pyrimidine derivative (X) in refluxing chloroform affords 3,5-di-O-benzoylclevudine (XI), which is finally deprotected by treatment with n-butylamine in refluxing methanol. Compound (X) is obtained by treatment of thymine (XII) with HMDS (1,1,1,3,3,3-hexamethyldisilazane) and ammonium sulfate in refluxing chloroform.
| 【1】 Almond, M.R.; Pesyan, A.; Sznaidman, M.L.; New synthesis of L-FMAU from L-arabinose. Nucleosides Nucleotides Nucleic Acids 2002, 21, 2, 155. |
| 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) | 48936 | D-Arabinose tetraacetate | C13H18O9 | 详情 | 详情 | |
| (III) | 54161 | (2R,3R,4S,5S)-3,5-bis(acetyloxy)-2-bromotetrahydro-2H-pyran-4-yl acetate | n/a | 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) | 54163 | (3R,4S,5S)-5-(acetyloxy)-3-fluoro-2-hydroxytetrahydro-2H-pyran-4-yl acetate | n/a | C9H13FO6 | 详情 | 详情 |
| (VI) | 54164 | (3R,4S,5S)-3-fluorotetrahydro-2H-pyran-2,4,5-triol | n/a | C5H9FO4 | 详情 | 详情 |
| (VII) | 54167 | (2S,3S,4R)-4-fluoro-2-(hydroxymethyl)-5-methoxytetrahydro-3-furanol | n/a | C6H11FO4 | 详情 | 详情 |
| (VIII) | 54165 | [(2S,3S,4R,5R)-3-(benzoyloxy)-4-fluoro-5-methoxytetrahydro-2-furanyl]methyl benzoate | n/a | C20H19FO6 | 详情 | 详情 |
| (IX) | 17524 | [(2S,3S,4R,5S)-3-(benzoyloxy)-5-bromo-4-fluorotetrahydro-2-furanyl]methyl benzoate | C19H16BrFO5 | 详情 | 详情 | |
| (X) | 41900 | 5-methyl-2,4-bis[(trimethylsilyl)oxy]pyrimidine; 5-methyl-2-[(trimethylsilyl)oxy]-4-pyrimidinyl trimethylsilyl ether | 7288-28-0 | C11H22N2O2Si2 | 详情 | 详情 |
| (XI) | 54166 | {(2S,3S,4R,5S)-3-(benzoyloxy)-4-fluoro-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl benzoate | n/a | C24H21FN2O7 | 详情 | 详情 |
| (XII) | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Synthesis of intermediate monosaccharide (VIII): The reaction of the tetraacetyl-L-arabinose (I) with Ph-SH and SnCl4 gives the thioglycoside (II), which is deacetylated with NaOMe in methanol, yielding compound (III). The reaction of (III) with 2,2-dimethoxypropane (IV) and CSA in dichloromethane affords the acetonide (V), which is acetylated with Ac2O, DMAP and TEA to provide the acetate (VI). Elimination of the acetonide group of (VI) with Amberlite IR-118B furnishes diol (VII), which is selectively silylated with Tes-OTf and lutidine in dichloromethane to afford the desired intermediate monosaccharide (VIII).
| 【1】 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369. |
| 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) | 48936 | D-Arabinose tetraacetate | C13H18O9 | 详情 | 详情 | |
| (II) | 48937 | (2S,3R,4S,5S)-3,5-bis(acetoxy)-2-(phenylsulfanyl)tetrahydro-2H-pyran-4-yl acetate | C17H20O7S | 详情 | 详情 | |
| (III) | 48938 | (2S,3R,4S,5S)-2-(phenylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol | C11H14O4S | 详情 | 详情 | |
| (IV) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (V) | 48939 | (3aS,6S,7R,7aR)-2,2-dimethyl-6-(phenylsulfanyl)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-ol | C14H18O4S | 详情 | 详情 | |
| (VI) | 48940 | (3aS,6S,7R,7aS)-2,2-dimethyl-6-(phenylsulfanyl)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-yl acetate | C16H20O5S | 详情 | 详情 | |
| (VII) | 48941 | (2S,3R,4S,5S)-4,5-dihydroxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl acetate | C13H16O5S | 详情 | 详情 | |
| (VIII) | 48942 | (2S,3R,4R,5S)-4-hydroxy-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl acetate | C19H30O5SSi | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I). L- Arabinose monosaccharide intermediate (VIII): The reaction of tetraacetyl-L-arabinose (I) with Ph-SH by means of SnCl4 in dichloromethane gives the acetylated thioglycoside (II), which is deacetylated by means of NaOMe in methanol to yield thioglycoside (III). The reaction of (III) with 2,2-dimethoxypropane (IV) and CSA in dichloromethane affords the acetonide (V), which is acetylated with Ac2O, TEA and DMAP to provide monoacetate (VI). The cleavage of the acetonide group of (VI) by means of Amberlite IR-118H leads to the monoacetylated thioglycoside (VII), which is finally selectively monosilylated with Tms-OTf and lutidine in dichloromethane the target L-arabinose intermediate (VIII)
| 【1】 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576. |
| 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) | 48936 | D-Arabinose tetraacetate | C13H18O9 | 详情 | 详情 | |
| (II) | 48937 | (2S,3R,4S,5S)-3,5-bis(acetoxy)-2-(phenylsulfanyl)tetrahydro-2H-pyran-4-yl acetate | C17H20O7S | 详情 | 详情 | |
| (III) | 48938 | (2S,3R,4S,5S)-2-(phenylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol | C11H14O4S | 详情 | 详情 | |
| (IV) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (V) | 48939 | (3aS,6S,7R,7aR)-2,2-dimethyl-6-(phenylsulfanyl)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-ol | C14H18O4S | 详情 | 详情 | |
| (VI) | 48940 | (3aS,6S,7R,7aS)-2,2-dimethyl-6-(phenylsulfanyl)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-yl acetate | C16H20O5S | 详情 | 详情 | |
| (VII) | 48941 | (2S,3R,4S,5S)-4,5-dihydroxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl acetate | C13H16O5S | 详情 | 详情 | |
| (VIII) | 48942 | (2S,3R,4R,5S)-4-hydroxy-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl acetate | C19H30O5SSi | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(IX)D-xylose trichloroacetimidate intermediate (XVIII): The reaction of tetraacetyl-D-xylose (IX) with HBr/AcOH n dichloromethane gives the glycosyl bromide (X), which is treated with Et-SH and lutidine in nitromethane to yield the thio orthoester (XI). The deacetylation of (XI) by means of NaOMe in methanol affords dihydroxy compound (XII), whose OH groups are protected by means of Pmb-Cl and NaH to provide the bis 4-methoxybenzyl ether compound (XIII). ZnCl2 promoted ring opening of the thio orthoester group of (XIII) leads to the thioglycoside (XIV), which is deacetylated by means of NaOMe in methanol to give compound (XV). The acylation of the free OH group of (XV) with 4-methoxybenzoyl chloride (XVI), TEA and DMAP in dichloromethane yields the benzoate ester (XVII), which is finally converted into the target D-xylose trichloroacetimidate (XVIII) by reaction with NBS, Cl3C-CN and DBU in dichloromethane
| 【1】 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 48936 | D-Arabinose tetraacetate | C13H18O9 | 详情 | 详情 | |
| (X) | 23761 | (2R,3R,4S,5R)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate | C11H15BrO7 | 详情 | 详情 | |
| (XI) | 60144 | (2S,3aR,6R,7S,7aR)-6-(acetyloxy)-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl acetate | C14H22O7S | 详情 | 详情 | |
| (XII) | 60145 | (2S,3aR,6R,7S,7aR)-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-6,7-diol | C10H18O5S | 详情 | 详情 | |
| (XIII) | 60146 | (2S,3aR,6R,7S,7aR)-6,7-bis[(4-methoxybenzyl)oxy]-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran; (2S,3aR,6R,7S,7aR)-6-[(4-methoxybenzyl)oxy]-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl 4-methoxybenzyl ether | C26H34O7S | 详情 | 详情 | |
| (XIV) | 60147 | (2S,3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-yl acetate | C26H34O7S | 详情 | 详情 | |
| (XV) | 60149 | (2S,3R,4R,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-ol | C24H32O6S | 详情 | 详情 | |
| (XVI) | 60148 | 4-methoxybenzoic acid | C8H8O3 | 详情 | 详情 | |
| (XVII) | 60150 | (2S,3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-yl 4-methoxybenzoate | C32H38O8S | 详情 | 详情 | |
| (XVIII) | 48950 | (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate | C31H32Cl3NO9 | 详情 | 详情 |