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【结 构 式】 
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【分子编号】59100 【品名】(1R)-1-(2-{[(3R,4R,5S,6R)-3-azido-5-{[bis(allyloxy)phosphoryl]oxy}-2-hydroxy-6-(methoxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate 【CA登记号】 |
【 分 子 式 】C35H62N3O10P 【 分 子 量 】715.865262 【元素组成】C 58.72% H 8.73% N 5.87% O 22.35% P 4.33% |
合成路线1
该中间体在本合成路线中的序号：(XXXV)The common precursor (XVIII) was converted into building block (XXXV) as follows. Esterification of (XVIII) with the unsaturated fatty acid (XXIX) by means of DCC and DMAP gave ester (XXX). The acetonide group of (XXX) was then hydrolyzed to diol (XXXI) under acidic conditions. Methylation of (XXXI) with iodomethane in the presence of silver oxide produced a mixture of two regioisomeric methyl ethers. In this mixture, the undesired 4-methoxy compound (XXXIII) was then selectively silylated at the free primary 6-hydroxyl group, which allowed chromatographic separation from the target 6-methoxy compound (XXXII). Phosphitylation of (XXXII), followed by oxidation of the intermediate phosphite with m-chloroperbenzoic acid, furnished phosphate (XXXIV). Desilylation of (XXXIV) to the required intermediate (XXXV) was accomplished by treatment with HF in acetonitrile.
| 【1】 Christ, W.J.; Kawata, T.; Hawkins, L.D.; Kobayashi, S.; Asano, O.; Rossignol, D.P. (Eisai Co., Ltd.); Anti-endotoxin cpds.. EP 0536969; JP 1993194470; US 5530113 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 59085 | (3R)-1-[((4aR,6S,7R,8R,8aS)-7-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)oxy]-3-decanol | C25H49N3O6Si | 详情 | 详情 | |
| (XXIX) | 49124 | (Z)-5-dodecenoic acid | C12H22O2 | 详情 | 详情 | |
| (XXX) | 59095 | (1R)-1-{2-[((4aR,6S,7R,8R,8aS)-7-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)oxy]ethyl}octyl (Z)-5-dodecenoate | C37H69N3O7Si | 详情 | 详情 | |
| (XXXI) | 59096 | (1R)-1-(2-{[(2S,3R,4R,5S,6R)-3-azido-2-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate | C34H65N3O7Si | 详情 | 详情 | |
| (XXXII) | 59097 | (1R)-1-(2-{[(2S,3R,4R,5S,6R)-3-azido-2-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-6-(methoxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate | C35H67N3O7Si | 详情 | 详情 | |
| (XXXIII) | 59098 | (1R)-1-(2-{[(2S,3R,4R,5S,6R)-3-azido-2-{[tert-butyl(dimethyl)silyl]oxy}-6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-methoxytetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate | C51H85N3O7Si2 | 详情 | 详情 | |
| (XXXIV) | 59099 | (1R)-1-(2-{[(2S,3R,4R,5S,6R)-3-azido-5-{[bis(allyloxy)phosphoryl]oxy}-2-{[tert-butyl(dimethyl)silyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate | C41H76N3O10PSi | 详情 | 详情 | |
| (XXXV) | 59100 | (1R)-1-(2-{[(3R,4R,5S,6R)-3-azido-5-{[bis(allyloxy)phosphoryl]oxy}-2-hydroxy-6-(methoxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate | C35H62N3O10P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXV)The hydroxyl group of (XXXV) was activated by treatment with trichloroacetonitrile to produce the corresponding trichloroacetimidate (XXXVI) as a diastereomeric mixture, which was used without separation. Coupling between imidates (XXXVI) and building block (XXIII) was accomplished by means of trimethylsilyl triflate, producing the disaccharide derivative (XXXVII). The azido groups of (XXXVII) were then reduced employing tin(II)tris-benzenethiolate triethylamine complex to afford diamine (XXXVIII).
| 【1】 Christ, W.J.; Kawata, T.; Hawkins, L.D.; Kobayashi, S.; Asano, O.; Rossignol, D.P. (Eisai Co., Ltd.); Anti-endotoxin cpds.. EP 0536969; JP 1993194470; US 5530113 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXVIa) | 59101 | (1R)-1-[2-({(2S,3R,4R,5S,6R)-3-azido-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-4-yl}oxy)ethyl]octyl (Z)-5-dodecenoate | C37H62Cl3N4O10P | 详情 | 详情 | |
| (XXXVIb) | 59102 | (1R)-1-[2-({(2R,3R,4R,5S,6R)-3-azido-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-4-yl}oxy)ethyl]octyl (Z)-5-dodecenoate | C37H62Cl3N4O10P | 详情 | 详情 | |
| (XXIII) | 59090 | allyl (1R)-1-(2-{[(2R,3S,4R,5R,6S)-3-{[(allyloxy)carbonyl]oxy}-5-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl carbonate | C30H53N3O10Si | 详情 | 详情 | |
| (XXXV) | 59100 | (1R)-1-(2-{[(3R,4R,5S,6R)-3-azido-5-{[bis(allyloxy)phosphoryl]oxy}-2-hydroxy-6-(methoxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate | C35H62N3O10P | 详情 | 详情 | |
| (XXXVII) | 59103 | (1R)-1-(2-{[(2R,3R,4R,5S,6R)-2-[((2R,3S,4R,5R,6S)-3-{[(allyloxy)carbonyl]oxy}-4-[((3R)-3-{[(allyloxy)carbonyl]oxy}decyl)oxy]-5-azido-6-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-2-yl)methoxy]-3-azido-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate | C65H113N6O19PSi | 详情 | 详情 | |
| (XXXVIII) | 59104 | (1R)-1-(2-{[(2R,3R,4R,5S,6R)-2-[((2R,3S,4R,5R,6S)-3-{[(allyloxy)carbonyl]oxy}-4-[((3R)-3-{[(allyloxy)carbonyl]oxy}decyl)oxy]-5-amino-6-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-2-yl)methoxy]-3-amino-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate | C65H117N2O19PSi | 详情 | 详情 |