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【结 构 式】 
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【分子编号】30933 【品名】tert-butyl (3aR,4S,7R,7aS)-4-(acetamido)-7-(hydroxymethyl)-2-phenyltetrahydro[1,3]dioxolo[4,5-c]pyridine-5(4H)-carboxylate 【CA登记号】 |
【 分 子 式 】C20H28N2O6 【 分 子 量 】392.4522 【元素组成】C 61.21% H 7.19% N 7.14% O 24.46% |
合成路线1
该中间体在本合成路线中的序号：(V)The protection of the NH group of siastatin B (I) with tert-butoxycarbonyl anhydride gives the N-protected intermediate (II), which is treated with benzaldehyde diethyl acetal and trimethylchlorosilane yielding the benzylidene ketal (III). The esterification of (III) with chloromethyl(2-methoxyethyl)ether and DIEA in DMF affords the activated ester (IV), which is reduced with NaBH4 in trifluoroethanol/THF giving the carbinol (V). The deacetylation of (V) with hot hydrazine yields the 2-aminopiperidine (VI), which is treated with ethyl trifluoroacetate and DIEA in hot DMF to afford the trifluoroacetamide (VII). The debenzylation of the cyclic ketal of (VII) with H2 over Pd/C in methanol gives the protected intermediate (VIII), which is finally deprotected with 4N HCl in hot dioxane.
| 【1】 Satoh, T.; et al.; A practical synthesis from siastatin B of (3S,4S, 5R,6R)-4,5-dihydroxy-6-(trifluoroacetamido)piperidine-3-carboxylic acid having antimetastatic activity in mice. Carbohydr Res 1996, 286, 173-178. |
| 【2】 Shitara, E.; A facile synthesis of D-galactose-type gem-diamine 1-N-iminosugar: A new family of galactosidase inhibitor. J Antibiot 1999, 52, 3, 348. |
| 【3】 Takeuchi, T.; Nishimura, Y.; Shitara, E. (Meiji Seika Kaisha, Ltd.; Microbial Chemistry Research Foundation); Siastatin B derivs. having glycosidase inhibitory activities and process for producing the same. EP 1142900; WO 0039140 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 27515 | Methoxy(phenyl)methyl methyl ether; Dimethylacetal benzaldehyde; Benzaldehyde dimethylacetal | 1125-88-8 | C9H12O2 | 详情 | 详情 | |
| 40670 | 2-(chloromethoxy)ethyl methyl ether; 1-(chloromethoxy)-2-methoxyethane; (2-methoxyethoxy)methyl chloride | 3970-21-6 | C4H9ClO2 | 详情 | 详情 | |
| (I) | 30929 | (3S,4S,5R,6R)-6-(acetamido)-4,5-dihydroxy-3-piperidinecarboxylic acid | C8H14N2O5 | 详情 | 详情 | |
| (II) | 30930 | (3S,4S,5R,6S)-6-(acetamido)-1-(tert-butoxycarbonyl)-4,5-dihydroxy-3-piperidinecarboxylic acid | C13H22N2O7 | 详情 | 详情 | |
| (III) | 30931 | (3aR,4S,7S,7aS)-4-(acetamido)-5-(tert-butoxycarbonyl)-2-phenylhexahydro[1,3]dioxolo[4,5-c]pyridine-7-carboxylic acid | C20H26N2O7 | 详情 | 详情 | |
| (IV) | 30932 | 5-(tert-butyl) 7-[(2-methoxyethoxy)methyl] (3aR,4S,7S,7aS)-4-(acetamido)-2-phenyltetrahydro[1,3]dioxolo[4,5-c]pyridine-5,7(4H)-dicarboxylate | C24H34N2O9 | 详情 | 详情 | |
| (V) | 30933 | tert-butyl (3aR,4S,7R,7aS)-4-(acetamido)-7-(hydroxymethyl)-2-phenyltetrahydro[1,3]dioxolo[4,5-c]pyridine-5(4H)-carboxylate | C20H28N2O6 | 详情 | 详情 | |
| (VI) | 30934 | tert-butyl (3aR,4S,7R,7aS)-4-amino-7-(hydroxymethyl)-2-phenyltetrahydro[1,3]dioxolo[4,5-c]pyridine-5(4H)-carboxylate | C18H26N2O5 | 详情 | 详情 | |
| (VII) | 30935 | tert-butyl (3aR,4S,7R,7aS)-7-(hydroxymethyl)-2-phenyl-4-[(2,2,2-trifluoroacetyl)amino]tetrahydro[1,3]dioxolo[4,5-c]pyridine-5(4H)-carboxylate | C20H25F3N2O6 | 详情 | 详情 | |
| (VIII) | 30936 | tert-butyl (2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-[(2,2,2-trifluoroacetyl)amino]-1-piperidinecarboxylate | C13H21F3N2O6 | 详情 | 详情 |