(4aR,6R,7R,8R,8aS)-7-amino-6-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol -Drug Synthesis Database

【结构式】

【分子编号】16046

【品名】(4aR,6R,7R,8R,8aS)-7-amino-6-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol

【CA登记号】

【分子式】C₁₆H₂₃NO₅

【分子量】309.36236

【元素组成】C 62.12% H 7.49% N 4.53% O 25.86%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IX)

2) The acylation of the amine group of benzyl 2-amino-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyranoside (IX) with 3(S)-hydroxytetradecanoic acid (II) by means of pivaloyl chloride in THF gives the corresponding amide (X), which is acylated with 9-phenylnonanoic acid (IV), 2-chloro-1-methylpyridinium iodide (CMPI) and dimethylaminopyridine to yield the fully esterified compound (XI). Elimination of the isopropylidene group of (XI) with acetic acid/water affords the dihydroxy compound (XII), which is treated with tert-butyldimethylsilyl chloride and DMAP to give (XIII) with the primary OH-group protected with a TBDMS group. Elimination of the benzyl protecting group of (XIII) by hydrogenation as before gives 2-deoxy-6-O-(tert-butyldimethylsilyl)-3-O-(9-phenylnonanoyl)-2-[3(S)-(9-phenylnonanoyloxy)tetradecanamido]-D-glucopyranose (XIV), which is sulfonated with SO3/pyridine complex in pyridine yielding the 4-O-sulfonated compound (XV). Finally, this compound is desilylated by means of acetic acid in methanol.

参考文献中间体

合成目标

【1】 Toda, M.; Shimoji, K.; Sasaki, Y. (Ono Pharmaceutical Co., Ltd.); Novel glucopyranose derivs. EP 0226381; JP 1988179885 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	16039	(3S)-3-hydroxytetradecanoic acid	1961-72-4	C₁₄H₂₈O₃	详情	详情
(IV)	16041	9-phenylnonanoic acid		C₁₅H₂₂O₂	详情	详情
(IX)	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
(X)	16047	(3S)-N-[(4aR,6R,7R,8R,8aS)-6-(benzyloxy)-8-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]-3-hydroxytetradecanamide		C₃₀H₄₉NO₇	详情	详情
(XI)	16048	(1S)-1-[2-([(4aR,6R,7R,8R,8aR)-6-(benzyloxy)-2,2-dimethyl-8-[(9-phenylnonanoyl)oxy]hexahydropyrano[3,2-d][1,3]dioxin-7-yl]amino)-2-oxoethyl]dodecyl 9-phenylnonanoate		C₆₀H₈₉NO₉	详情	详情
(XII)	16049	(2R,3R,4R,5R,6R)-2-(benzyloxy)-5-hydroxy-6-(hydroxymethyl)-3-([(3S)-3-[(9-phenylnonanoyl)oxy]tetradecanoyl]amino)tetrahydro-2H-pyran-4-yl 9-phenylnonanoate		C₅₇H₈₅NO₉	详情	详情
(XIII)	16050	(2R,3R,4R,5R,6R)-2-(benzyloxy)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-5-hydroxy-3-([(3S)-3-[(9-phenylnonanoyl)oxy]tetradecanoyl]amino)tetrahydro-2H-pyran-4-yl 9-phenylnonanoate		C₆₃H₉₉NO₉Si	详情	详情
(XIV)	16044	(2R,3R,4R,5R)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3,6-dihydroxy-5-([(3S)-3-[(9-phenylnonanoyl)oxy]tetradecanoyl]amino)tetrahydro-2H-pyran-4-yl 9-phenylnonanoate		C₅₆H₉₃NO₉Si	详情	详情
(XV)	16052	6-O-(Tert-butyldimethylsilyl)-2-deoxy-3-O-(9-phenylnonanoyl)-2-[3(S)-(9-phenylnonanoyloxy)tetradecanamido]-4-O-sulfo-D-glucopyranose sodium salt		C₅₆H₉₂NNaO₁₂SSi	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Acylation of amino alcohol (I) with (R)-3-(n-tetradecanoyloxy)tetradecanoic acid (II) employing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (EDC.MeI) provided amide (III). After hydroxyl group protection with 2,2,2-trichloroethyl chloroformate (A), the resulting acetonide (IV) was hydrolyzed with aqueous AcOH to give (V).

参考文献中间体

合成目标

【1】 Sowell, C.G.; Johnson, D.A.; Keegan, D.S.; et al.; 3-O-Desacyl monophosphoryl lipid A derivatives: Synthesis and immunostimulant activities. J Med Chem 1999, 42, 22, 4640.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	13664	1,1,1-Trichloro-2-[(chlorocarbonyl)oxy]ethane; 2,2,2-Trichloroethyl chloroformate	17341-93-4	C₃H₂Cl₄O₂	详情	详情
(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)	40612	(3R)-3-(tetradecanoyloxy)tetradecanoic acid		C₂₈H₅₄O₄	详情	详情
(III)	40613	(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 myristate		C₄₄H₇₅NO₈	详情	详情
(IV)	40614	(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 myristate		C₄₇H₇₆Cl₃NO₁₀	详情	详情
(V)	40615	(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 myristate		C₄₄H₇₂Cl₃NO₁₀	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

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

合成目标

【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

Extended Information