benzhydryl (2S,3R,4R,5S,6R)-3-{[(3R)-3-(benzyloxy)tetradecanoyl]amino}-4-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】57535

【品名】benzhydryl (2S,3R,4R,5S,6R)-3-{[(3R)-3-(benzyloxy)tetradecanoyl]amino}-4-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxylate

【CA登记号】

【分子式】C₆₂H₈₉NO₉

【分子量】992.39

【元素组成】C 75.04% H 9.04% N 1.41% O 14.51%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XI)

The functionalized glucosamine building block (XI) is prepared as follows. Allyl 2-amino-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyranoside (I) is converted into azide (II) upon treatment with trifluoromethanesulfonyl azide and DMAP. Alkylation of the free hydroxyl group of (II) with mesylate (III) in the presence of NaH gives ether (IV). The O-allyl group of (IV) is then removed by iridium-catalyzed double bond isomerization, followed by oxidative hydrolysis with iodine and pyridine, to afford (V). Condensation of (V) with trichloroacetonitrile produces imidate (VI), which is further displaced with trimethylsilyl cyanide, yielding nitrile (VII). Reduction of the azido group of (VII) by means of triphenylphosphine affords amine (VIII). This is acylated by (R)-3-(benzyloxy)tetradecanoic acid (IX) in the presence of DCC and DMAP, yielding amide (X). Acidic hydrolysis of the cyano group, followed by reaction of the resultant carboxylic acid with diphenyldiazomethane, leads to the benzhydryl ester (XI).

参考文献中间体

合成目标

【1】 Shiozaki, M.; Kurakata, S.; Kanai, S.; Kazama, Y. (Sankyo Co., Ltd.); Ether type lipid A1-carboxylic acid analogues. EP 1152007; JP 2000297096; US 2002161221; US 6511965; WO 0047595 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	57525	(4aR,6R,7R,8R,8aS)-6-(allyloxy)-7-amino-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol	C₁₂H₂₁NO₅	详情	详情
(II)	57526	(4aR,6R,7R,8R,8aS)-6-(allyloxy)-7-azido-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol	C₁₂H₁₉N₃O₅	详情	详情
(III)	57527	3-(benzyloxy)propyl methanesulfonate	C₁₁H₁₆O₄S	详情	详情
(IV)	57528	(4aR,6R,7R,8R,8aS)-6-(allyloxy)-7-azido-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl (3R)-3-(benzyloxy)tetradecyl ether; (4aR,6R,7R,8R,8aS)-6-(allyloxy)-7-azido-8-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine	C₃₃H₅₃N₃O₆	详情	详情
(V)	57529	(4aR,7R,8R,8aS)-7-azido-8-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-ol	C₃₀H₄₉N₃O₆	详情	详情
(VI)	57530	(4aR,6R,7R,8R,8aS)-7-azido-8-[3-(benzyloxy)propoxy]-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl 2,2,2-trichloroethanimidoate	C₂₁H₂₇Cl₃N₄O₆	详情	详情
(VII)	57531	(4aR,6S,7R,8R,8aS)-7-azido-8-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carbonitrile	C₃₁H₄₈N₄O₅	详情	详情
(VIII)	57532	(4aR,6S,7R,8R,8aS)-7-amino-8-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine-6-carbonitrile	C₃₁H₅₀N₂O₅	详情	详情
(IX)	57533	(3R)-3-(benzyloxy)tetradecanoic acid	C₂₁H₃₄O₃	详情	详情
(X)	57534	(3R)-N-((4aR,6S,7R,8R,8aS)-8-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-6-cyano-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)-3-(benzyloxy)tetradecanamide	C₅₂H₈₂N₂O₇	详情	详情
(XI)	57535	benzhydryl (2S,3R,4R,5S,6R)-3-{[(3R)-3-(benzyloxy)tetradecanoyl]amino}-4-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxylate	C₆₂H₈₉NO₉	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

The glucosamine derivative (XXVIII) is activated as the imidate (XXIX), upon treatment with trichloroacetonitrile and DBU, and subsequently coupled with (XI) in the presence of trimethylsilyl triflate, to afford disaccharide (XXX). The trichloroethoxycarbonyl protecting group of (XXX) is then removed by reductive treatment with zinc and acetic acid, producing amine (XXXI), which is subsequently acetylated with Ac2O, to afford acetamide (XXXII).

参考文献中间体

合成目标

【1】 Nishijima, M.; Kurakata, S.-I.; Shiozaki, M.; Mochizuki, T.; Kanai, S.; Watanabe, Y.; Synthesis of lipid A type pyran carboxylic acids with ether chains and their biological activities. Carbohydr Res 2001, 333, 3, 203.
【2】 Shiozaki, M.; Kurakata, S.; Kanai, S.; Kazama, Y. (Sankyo Co., Ltd.); Ether type lipid A1-carboxylic acid analogues. EP 1152007; JP 2000297096; US 2002161221; US 6511965; WO 0047595 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XI)	57535	benzhydryl (2S,3R,4R,5S,6R)-3-{[(3R)-3-(benzyloxy)tetradecanoyl]amino}-4-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxylate	C₆₂H₈₉NO₉	详情	详情
(XXVIII)	57551	(1R)-1-{2-[((2R,3S,4R,5R)-3-[(diphenoxyphosphoryl)oxy]-6-hydroxy-2-(methoxymethyl)-5-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-4-yl)oxy]ethyl}dodecyl myristate	C₅₀H₇₉Cl₃NO₁₂P	详情	详情
(XXIX)	57552	(1R)-1-{2-[((2R,3S,4R,5R)-3-[(diphenoxyphosphoryl)oxy]-2-(methoxymethyl)-6-[(2,2,2-trichloroethanimidoyl)oxy]-5-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-4-yl)oxy]ethyl}dodecyl myristate	C₅₂H₇₉Cl₆N₂O₁₂P	详情	详情
(XXX)	57553	benzhydryl (2S,3R,4R,5S,6R)-3-{[(3R)-3-(benzyloxy)tetradecanoyl]amino}-4-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-6-{[((2R,3R,4R,5S,6R)-5-[(diphenoxyphosphoryl)oxy]-6-(methoxymethyl)-4-{[(3R)-3-(tetradecanoyloxy)tetradecyl]oxy}-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-2-yl)oxy]methyl}-5-hydroxytetrahydro-2H-pyran-2-carboxylate	C₁₁₂H₁₆₆Cl₃N₂O₂₀P	详情	详情
(XXXI)	57554	benzhydryl (2S,3R,4R,5S,6R)-6-{[((2R,3R,4R,5S,6R)-3-amino-5-[(diphenoxyphosphoryl)oxy]-6-(methoxymethyl)-4-{[(3R)-3-(tetradecanoyloxy)tetradecyl]oxy}tetrahydro-2H-pyran-2-yl)oxy]methyl}-3-{[(3R)-3-(benzyloxy)tetradecanoyl]amino}-4-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-5-hydroxytetrahydro-2H-pyran-2-carboxylate	C₁₀₉H₁₆₅N₂O₁₈P	详情	详情
(XXXII)	57555	benzhydryl (2S,3R,4R,5S,6R)-6-{[((2R,3R,4R,5S,6R)-3-(acetylamino)-5-[(diphenoxyphosphoryl)oxy]-6-(methoxymethyl)-4-{[(3R)-3-(tetradecanoyloxy)tetradecyl]oxy}tetrahydro-2H-pyran-2-yl)oxy]methyl}-3-{[(3R)-3-(benzyloxy)tetradecanoyl]amino}-4-{[(3R)-3-(benzyloxy)tetradecyl]oxy}-5-hydroxytetrahydro-2H-pyran-2-carboxylate	C₁₁₁H₁₆₇N₂O₁₉P	详情	详情

Extended Information