2,2,2-trichloroethyl (3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-2-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-3-ylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】64154

【品名】2,2,2-trichloroethyl (3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-2-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-3-ylcarbamate

【CA登记号】

【分子式】C₂₇H₄₇Cl₃NO₁₁P

【分子量】699.002182

【元素组成】C 46.39% H 6.78% Cl 15.22% N 2% O 25.18% P 4.43%

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：(XXI)

Displacement of the tosylate group of (XV) by sodium methoxide produced the methyl ether (XVI). Hydrolysis of the trifluoroacetamide function of (XVI) using potassium tert-butoxide in hot DMSO took place with simultaneous allylic double bond isomerization, leading to enol ether (XVII). After protection of the amino group of (XVII) as the trichloroethyl carbamate (XVIII), phosphitylation of the secondary hydroxyl group of (XVIII) with diallyl N,N-diisopropylphosphoramidite in the presence of tetrazole-generated phosphite (XIX), which was further oxidized to phosphate (XX) employing Oxone (R). The O-propenyl group of (XX) was then hydrolyzed by means of HF to provide the monosaccharide building block (XXI).

参考文献中间体

合成目标

【1】 Kobayashi, S.; Kawata, T.; Christ, W.J.; Rossignol, D.P. (Eisai Co., Ltd.); Substd. liposaccharides useful in the treatment and prevention of endotoxemia. US 5750664; WO 9639411 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XV)	64148	{(2R,3S,4R,5R)-6-(allyloxy)-3-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-5-[(2,2,2-trifluoroacetyl)amino]tetrahydro-2H-pyran-2-yl}methyl 4-methylbenzenesulfonate	C₂₉H₄₄F₃NO₉S	详情	详情
(XVI)	64149	N-[(3R,4R,5S,6R)-2-(allyloxy)-5-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-3-yl]-2,2,2-trifluoroacetamide	C₂₃H₄₀F₃NO₇	详情	详情
(XVII)	64150	(2R,3S,4R,5R)-5-amino-4-{[(3R)-3-methoxydecyl]oxy}-2-(methoxymethyl)-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ol	C₂₁H₄₁NO₆	详情	详情
(XVIII)	64151	2,2,2-trichloroethyl (3R,4R,5S,6R)-5-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-2-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ylcarbamate	C₂₄H₄₂Cl₃NO₈	详情	详情
(XIX)	64152	2,2,2-trichloroethyl (3R,4R,5S,6R)-5-{[bis(allyloxy)phosphino]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-2-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ylcarbamate	C₃₀H₅₁Cl₃NO₁₀P	详情	详情
(XX)	64153	2,2,2-trichloroethyl (3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-2-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ylcarbamate	C₃₀H₅₁Cl₃NO₁₁P	详情	详情
(XXI)	64154	2,2,2-trichloroethyl (3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-2-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-3-ylcarbamate	C₂₇H₄₇Cl₃NO₁₁P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXI)

Monosaccharide (XXI) was activated as the trichloroacetimidate (XXXIV) upon treatment with trichloracetonitrile. Coupling between the protected monosaccharide (XXXIII) and imidate (XXXIV) using silver triflate as the coupling promoter produced the protected disaccharide adduct (XXXV). After reductive cleavage of the trichloroethyl carbamate protecting group of (XXXV), the resultant amine (XXXVI) was acylated with vaccenoyl chloride (XXXVII) giving amide (XXXVIII).

参考文献中间体

合成目标

【1】 Kobayashi, S.; Kawata, T.; Christ, W.J.; Rossignol, D.P. (Eisai Co., Ltd.); Substd. liposaccharides useful in the treatment and prevention of endotoxemia. US 5750664; WO 9639411 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXI)	64154	2,2,2-trichloroethyl (3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-2-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-3-ylcarbamate	C₂₇H₄₇Cl₃NO₁₁P	详情	详情
(XXXIII)	64165	allyl (2R,3S,4R,5R)-4-(decyloxy)-2-(hydroxymethyl)-5-[(3-oxotetradecanoyl)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate	C₃₇H₆₅NO₉	详情	详情
(XXXIV)	64166	(3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-2-yl 2,2,2-trichloroethanimidoate	C₂₉H₄₇Cl₆N₂O₁₁P	详情	详情
(XXXV)	64167	allyl (2R,3S,4R,5R)-2-{[((2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-2-yl)oxy]methyl}-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate	C₆₄H₁₁₀Cl₃N₂O₁₉P	详情	详情
(XXXVI)	64168	allyl (2R,3S,4R,5R)-2-({[(2R,3R,4R,5S,6R)-3-amino-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-2-yl]oxy}methyl)-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate	C₆₁H₁₀₉N₂O₁₇P	详情	详情
(XXXVII)	64169	(Z)-11-octadecenoyl chloride	C₁₈H₃₃ClO	详情	详情
(XXXVIII)	64170	allyl (2R,3S,4R,5R)-2-[({(2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-[(Z)-11-octadecenoylamino]tetrahydro-2H-pyran-2-yl}oxy)methyl]-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate	C₇₉H₁₄₁N₂O₁₈P	详情	详情

Extended Information