新产品编号:1527139
Chemical Name: (2R,3R,4S,5R)-N-[3,4-Dihydroxy-5-(hydroxymethyl)piperidin-2-yl]-2,2,2-trifluoroacetamide
项目整合开发状态: Biological Testing
项目研究机构: Microbial Chemistry Research Foundation (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Siastatin B derivs.having glycosidase inhibitory activities and process for producing the same
文献作者:Takeuchi,T.; Nishimura,Y.; Shitara,E.(Meiji Seika Kaisha,Ltd.; Microbial Chemistry Research Foundation)
参考来源:EP 1142900; WO 0039140
📄 详细内容
合成路线: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.
参考文献标题:A facile synthesis of D-galactose-type gem-diamine 1-N-iminosugar: A new family of galactosidase inhibitor
文献作者:Shitara,E.; Nishimura,Y.; Kojima,F.; Takeuchi,T.
参考来源:J Antibiot 1999,52(3),348
合成路线: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.
参考文献标题: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
文献作者:Satoh,T.; et al.
参考来源:Carbohydr Res 1996,286173-178