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【结 构 式】 
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【分子编号】58302 【品名】(3R,4R,5R)-5-(hydroxymethyl)-3,4-piperidinediol 【CA登记号】 |
【 分 子 式 】C6H13NO3 【 分 子 量 】147.17416 【元素组成】C 48.97% H 8.9% N 9.52% O 32.61% |
合成路线1
该中间体在本合成路线中的序号：(VII)The demethylation of 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester (I) by reaction with 1-chloroethyl chloroformate, followed by reaction with Boc2O gives 1-(tert-butoxycarbonyl) -1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester (II). The isomerization of (II) by means of LDA in THF yields 1-(tert-butoxycarbonyl) -1,2,3,6-tetrahydropyridine-3-carboxylic acid methyl ester (III), which is reduced with LiBHEt3 in THF to afford the hydroxymethyl derivative (IV). The reaction of (IV) with MCPBA in dichloromethane provides the epoxide (V), which is treated with refluxing aq. KOH, resulting in a racemic mixture of the enantiomers (VI) and (VII) as the major products. Finally, the target isofagomine is separated by chiral chromatography.
| 【1】 Kristiansen, M.; Jakobsen, P.; Lundbeck, J.M.; et al.; Iminosugars: Potential inhibitors of liver glycogen phosphorylase. Bioorg Med Chem 2001, 9, 3, 733. |
| 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) | 38648 | methyl 1-methyl-1,2,5,6-tetrahydro-3-pyridinecarboxylate | C8H13NO2 | 详情 | 详情 | |
| (II) | 58297 | 1-(tert-butyl) 3-methyl 5,6-dihydro-1,3(2H)-pyridinedicarboxylate | C12H19NO4 | 详情 | 详情 | |
| (III) | 58298 | 1-(tert-butyl) 3-methyl 3,6-dihydro-1,3(2H)-pyridinedicarboxylate | C12H19NO4 | 详情 | 详情 | |
| (IV) | 58299 | tert-butyl 3-(hydroxymethyl)-3,6-dihydro-1(2H)-pyridinecarboxylate | C11H19NO3 | 详情 | 详情 | |
| (V) | 58300 | tert-butyl 5-(hydroxymethyl)-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate | C11H19NO4 | 详情 | 详情 | |
| (VI) | 58301 | (3S,4R,5S)-3-(hydroxymethyl)-5-methyl-4-piperidinol | C7H15NO2 | 详情 | 详情 | |
| (VII) | 58302 | (3R,4R,5R)-5-(hydroxymethyl)-3,4-piperidinediol | C6H13NO3 | 详情 | 详情 |