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【结 构 式】 
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【分子编号】64151 【品名】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 【CA登记号】 |
【 分 子 式 】C24H42Cl3NO8 【 分 子 量 】578.95752 【元素组成】C 49.79% H 7.31% Cl 18.37% N 2.42% O 22.11% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)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).
| 【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 | CAS号 | 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：(XXVIII)The other monosaccharide building block (XXXIII) was also synthesized from the common intermediate (XII). Alkylation of (XII) with mesylate (XXIII), prepared from 1-decanol (XXII), gave the decyl ether (XXIV). After acidic acetonide hydrolysis of (XXIV) to yield (XXV), removal of the trifluoroacetamide by means of potassium tert-butoxide, with concomitant O-allyl group isomerization, furnished (XXVI). Imine (XXVII) was then obtained by exchange reaction of amine (XXVI) with benzophenone imine at 45 C. After silylation of the primary hydroxyl of (XXVII) with tert-butyldimethylsilyl chloride affording(XXVIII), the secondary hydroxyl group was protected as the allyl carbonate (XXIX) by sequential treatment with phosgene and then with allyl alcohol. Imine (XXIX) hydrolysis, followed by coupling of the resultant amine (XXX) with 3-oxotetradecanoic acid (XXXI) led to keto amide (XXXII). Precursor (XXXIII) was then obtained by desilylation of (XXXII) with HF.
| 【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 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 57540 | N-[(4aR,6S,7R,8R,8aS)-6-(allyloxy)-8-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]-2,2,2-trifluoroacetamide | C14H20F3NO6 | 详情 | 详情 | |
| (XXII) | 40729 | 1-decanol | 112-30-1 | C10H22O | 详情 | 详情 |
| (XXIII) | 64156 | decyl methanesulfonate | C11H24O3S | 详情 | 详情 | |
| (XXIV) | 64157 | N-[(4aR,7R,8R,8aS)-6-(allyloxy)-8-(decyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]-2,2,2-trifluoroacetamide | C24H40F3NO6 | 详情 | 详情 | |
| (XXV) | 64158 | N-[(3R,4R,5S,6R)-2-(allyloxy)-4-(decyloxy)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]-2,2,2-trifluoroacetamide | C21H36F3NO6 | 详情 | 详情 | |
| (XXVI) | 64159 | (2R,3S,4R,5R)-5-amino-4-(decyloxy)-2-(hydroxymethyl)-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ol | C19H37NO5 | 详情 | 详情 | |
| (XXVII) | 64160 | (2R,3S,4R,5R)-4-(decyloxy)-5-[(diphenylmethylene)amino]-2-(hydroxymethyl)-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ol | C32H45NO5 | 详情 | 详情 | |
| (XXVIII) | 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 | |
| (XXIX) | 64162 | allyl (2R,3S,4R,5R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(decyloxy)-5-[(diphenylmethylene)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate | C42H63NO7Si | 详情 | 详情 | |
| (XXX) | 64163 | allyl (2R,3S,4R,5R)-5-amino-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(decyloxy)-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate | C29H55NO7Si | 详情 | 详情 | |
| (XXXI) | 59107 | 3-oxotetradecanoic acid | C14H26O3 | 详情 | 详情 | |
| (XXXII) | 64164 | allyl (2R,3S,4R,5R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate | C43H79NO9Si | 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 |