-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】(2R,3R,4S,5R)-N-[3,4-Dihydroxy-5-(hydroxymethyl)piperidin-2-yl]-2,2,2-trifluoroacetamide

【CA登记号】

【分子式】C₈H₁₃F₃N₂O₄

【分子量】258.19901

【开发单位】Microbial Chemistry Research Foundation (Originator)

【药理作用】AIDS Medicines, Antidiabetic Drugs, Anti-HIV Agents, ANTIINFECTIVE THERAPY, ENDOCRINE DRUGS, ONCOLYTIC DRUGS, beta-Galactosidase Inhibitors

合成路线1

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.

参考文献中间体

【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

Extended Information

Drug NewChemical Entity Original Patent(1)