RC-552C, RC-552, -Drug Synthesis Database

【结构式】

【药物名称】RC-552C, RC-552

【化学名称】　

【CA登记号】253119-91-4

【分子式】C₁₀₂H₁₉₃N₂O₂₁P

【分子量】1814.65011

【开发单位】Corixa (Originator), CoPharma (Licensee)

【药理作用】Acute Myocardial Infarction, Treatment of, Cardioprotective Agents, CARDIOVASCULAR DRUGS, Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis

合成路线1 合成路线2 合成路线3

合成路线1

Coupling of protected 2-aminoglucopyranoside (I) with (R)-3-(hexadecanoyloxy)tetradecanoic acid (II) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide gave amide (III). After protection of the 3-hydroxyl group of (III) with 2,2,2-trichloroethyl chloroformate, acetonide hydrolysis with aqueous acetic acid provided intermediate (V).

参考文献中间体

【1】 Sowell, C.G.; Weber, P.A.; Elliott, G.T. (Corixa Corp.); Phosphoglycolipid and methods for its use. WO 0011010 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	16046	(4aR,6R,7R,8R,8aS)-7-amino-6-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol	C₁₆H₂₃NO₅	详情	详情
(II)	39765	(3R)-3-(palmitoyloxy)tetradecanoic acid	C₃₀H₅₈O₄	详情	详情
(III)	39766	(1R)-1-(2-[[(4aR,6R,7R,8R,8aS)-6-(benzyloxy)-8-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]amino]-2-oxoethyl)dodecyl palmitate	C₄₆H₇₉NO₈	详情	详情
(IV)	39767	(1R)-1-[2-[((4aR,6R,7R,8R,8aR)-6-(benzyloxy)-2,2-dimethyl-8-[[(2,2,2-trichloroethoxy)carbonyl]oxy]hexahydropyrano[3,2-d][1,3]dioxin-7-yl)amino]-2-oxoethyl]dodecyl palmitate	C₄₉H₈₀Cl₃NO₁₀	详情	详情
(V)	39768	(1R)-1-[2-[((2R,3R,4R,5R,6R)-2-(benzyloxy)-5-hydroxy-6-(hydroxymethyl)-4-[[(2,2,2-trichloroethoxy)carbonyl]oxy]tetrahydro-2H-pyran-3-yl)amino]-2-oxoethyl]dodecyl palmitate	C₄₆H₇₆Cl₃NO₁₀	详情	详情

合成路线2

Protection of the amino group of aminopyranoside (VI) with 2,2,2-trichloroethyl chloroformate under Schotten-Baumann conditions afforded trichloroethyl carbamate (VII). Subsequent O-acylation of (VII) with acid chloride (VIII) gave ester (IX). Acetonide (IX) cleavage with aqueous AcOH yielded diol (X), which was protected at the primary hydroxyl group using 1,1-dimethyl-2,2,2-trichloroethyl chloroformate yielding (XI). Conversion of (XI) to the required phosphate (XII) was effected by reaction with diphenyl chlorophosphate. The intermediate glycosyl chloride (XIII) was then obtained by treatment of (XII) with dichloromethyl methyl ether and ZnCl2.

参考文献中间体

【1】 Sowell, C.G.; Weber, P.A.; Elliott, G.T. (Corixa Corp.); Phosphoglycolipid and methods for its use. WO 0011010 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	39769	(4aR,6R,7R,8R,8aS)-7-amino-2,2-dimethyl-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-8-ol	C₁₄H₂₉NO₅Si	详情	详情
(VII)	39770	2,2,2-trichloroethyl (4aR,6R,7R,8R,8aS)-8-hydroxy-2,2-dimethyl-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-7-ylcarbamate	C₁₇H₃₀Cl₃NO₇Si	详情	详情
(VIII)	39771	(1R)-1-(2-chloro-2-oxoethyl)dodecyl myristate	C₂₈H₅₃ClO₃	详情	详情
(IX)	39772	(4aR,6R,7R,8R,8aR)-2,2-dimethyl-7-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-8-yl (3R)-3-(tetradecanoyloxy)tetradecanoate	C₄₅H₈₂Cl₃NO₁₀Si	详情	详情
(X)	39773	(2R,3R,4R,5R,6R)-3-hydroxy-2-(hydroxymethyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate	C₄₂H₇₈Cl₃NO₁₀Si	详情	详情
(XI)	39774	(2R,3R,4R,5R,6R)-3-hydroxy-2-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate	C₄₇H₈₃Cl₆NO₁₂Si	详情	详情
(XII)	39775	(2R,3R,4R,5R,6R)-3-[(diphenoxyphosphoryl)oxy]-2-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate	C₅₉H₉₂Cl₆NO₁₅PSi	详情	详情
(XIII)	39776	(2R,3R,4R,5S,6R)-2-chloro-5-[(diphenoxyphosphoryl)oxy]-3-[(ethoxycarbonyl)amino]-6-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate	C₅₄H₈₂Cl₄NO₁₄P	详情	详情

合成路线3

Coupling of intermediates (V) and (XIII) in the presence of silver triflate gave disaccharide (XIV). The trichloroethyl-based protecting groups of (XIV) were then removed with zinc dust in acetic acid to yield (XV). The glucosamine nitrogen of (XV) was selectively acylated with acid (XVI) to produce amide (XVII). The remaining protecting groups of (XVII) were finally removed by means of a two-phase catalytic hydrogenation employing palladium and platinum catalysts, yielding the title compound.

参考文献中间体

【1】 Sowell, C.G.; Weber, P.A.; Elliott, G.T. (Corixa Corp.); Phosphoglycolipid and methods for its use. WO 0011010 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	39768	(1R)-1-[2-[((2R,3R,4R,5R,6R)-2-(benzyloxy)-5-hydroxy-6-(hydroxymethyl)-4-[[(2,2,2-trichloroethoxy)carbonyl]oxy]tetrahydro-2H-pyran-3-yl)amino]-2-oxoethyl]dodecyl palmitate	C₄₆H₇₆Cl₃NO₁₀	详情	详情
(XIII)	39776	(2R,3R,4R,5S,6R)-2-chloro-5-[(diphenoxyphosphoryl)oxy]-3-[(ethoxycarbonyl)amino]-6-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate	C₅₄H₈₂Cl₄NO₁₄P	详情	详情
(XIV)	39777		C₁₀₀H₁₅₇Cl₆N₂O₂₄P	详情	详情
(XV)	39778		C₈₉H₁₄₇N₂O₁₈P	详情	详情
(XVI)	39779	(3R)-3-(stearoyloxy)tetradecanoic acid	C₃₂H₆₂O₄	详情	详情
(XVII)	39780		C₁₂₁H₂₀₇N₂O₂₁P	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)