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【结 构 式】 
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【分子编号】59104 【品名】(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 【CA登记号】 |
【 分 子 式 】C65H117N2O19PSi 【 分 子 量 】1289.705322 【元素组成】C 60.53% H 9.14% N 2.17% O 23.57% P 2.4% Si 2.18% |
合成路线1
该中间体在本合成路线中的序号：(XXXVIII)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 |
合成路线2
该中间体在本合成路线中的序号：(XXXVIII)Keto ester (XLI) was obtained by Reformatskii condensation of the organozinc reagent generated from benzyl bromoacetate (XL) with n-undecyl cyanide (XXXIX). Subsequent hydrogenolysis of the benzyl ester of (XLI) in the presence of Pearlman's catalyst furnished keto acid (XLII). Acylation of the diamino compound (XXXVIII) with ketoacid (XLII), by means of DCC, provided diamide (XLIII). Then, desilylation of (XLIII) to afford alcohol (XLIV) was accomplished employing 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 |
|---|---|---|---|---|---|---|
| (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 | |
| (XXXIX) | 59105 | lauronitrile | C12H23N | 详情 | 详情 | |
| (XL) | 12869 | benzyl 2-bromoacetate | 5437-45-6 | C9H9BrO2 | 详情 | 详情 |
| (XLI) | 59106 | benzyl 3-oxotetradecanoate | C21H32O3 | 详情 | 详情 | |
| (XLII) | 59107 | 3-oxotetradecanoic acid | C14H26O3 | 详情 | 详情 | |
| (XLIII) | 59108 | (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]-6-{[tert-butyl(dimethyl)silyl]oxy}-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-2-yl}methoxy)-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)-3-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-4-yl}oxy)ethyl]octyl (Z)-5-dodecenoate | C93H165N2O23PSi | 详情 | 详情 | |
| (XLIV) | 59109 | (1R)-1-[2-({(2R,3R,4R,5S,6R)-2-({(2R,3S,4R,5R)-3-{[(allyloxy)carbonyl]oxy}-4-[((3R)-3-{[(allyloxy)carbonyl]oxy}decyl)oxy]-6-hydroxy-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-2-yl}methoxy)-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)-3-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-4-yl}oxy)ethyl]octyl (Z)-5-dodecenoate | C87H151N2O23P | 详情 | 详情 |