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【结 构 式】 
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【分子编号】56363 【品名】N-{(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-hydroxytetrahydro-2H-pyran-3-yl}oxy)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}acetamide 【CA登记号】 |
【 分 子 式 】C51H58N2O11 【 分 子 量 】875.0284 【元素组成】C 70% H 6.68% N 3.2% O 20.11% |
合成路线1
该中间体在本合成路线中的序号：(XLVI)Condensation of the glucopyranosyl chloride (XXXIX) with the protected glucosamine (XL) in the presence of silver triflate-s-collidine complex gave disaccharide (XLI). Subsequent dephthaloylation and ester hydrolysis of (XLI) by means of n-butylamine in boiling MeOH furnished (XLII). Chemoselective acylation of the amino group of (XLII) with Ac2O in MeOH provided acetamide (XLIII). The free hydroxyl groups of (XLIII) were then protected as the corresponding benzyl ethers (XLIV) employing benzyl bromide in the presence of barium oxide and barium hydroxyde. The O-allyl group of (XLIV) was then isomerized in the presence of DABCO and rhodium catalyst to the 1-propenyl analogue (XLV), which was further hydrolyzed to alcohol (XLVI) by treatment with HgCl2.
| 【1】 Durette, P.L.; et al.; Synthesis of O-(2-acetamido-2-deoxy-beta-D-glucosyl)-(1--4)-N-acetylmuramoyl-L-alanyl-D-isoglutamine, the repeating disaccharide-dipeptide unit of the bacterial cell-wall peptidoglycan. Carbohydr Res 1979, 77, C1. |
| 【2】 Durette, P.L.; Shen, T.-Y. (Merck & Co., Inc.); Immunologically active peptidyl disaccharides, methods of preparation and vaccine. EP 0018901 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIX) | 56356 | (2R,3S,4R,5R,6S)-3-(acetyloxy)-2-[(acetyloxy)methyl]-6-chloro-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)tetrahydro-2H-pyran-4-yl acetate | C20H20ClNO9 | 详情 | 详情 | |
| (XL) | 56357 | N-{(2S,3R,4R,5S,6R)-4-(allyloxy)-2-(benzyloxy)-6-[(benzyloxy)methyl]-5-hydroxytetrahydro-2H-pyran-3-yl}acetamide | C25H31NO6 | 详情 | 详情 | |
| (XLI) | 56358 | (2R,3R,4R,5R,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-4-(allyloxy)-6-(benzyloxy)-2-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}oxy)-5-(acetyloxy)-6-[(acetyloxy)methyl]-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)tetrahydro-2H-pyran-4-yl acetate | C45H50N2O15 | 详情 | 详情 | |
| (XLII) | 56359 | N-{(2S,3R,4R,5S,6R)-4-(allyloxy)-5-{[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-2-(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}acetamide | C31H42N2O10 | 详情 | 详情 | |
| (XLIII) | 56360 | N-[(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-4-(allyloxy)-6-(benzyloxy)-2-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}oxy)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]acetamide | C33H44N2O11 | 详情 | 详情 | |
| (XLIV) | 56361 | N-{(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-4-(allyloxy)-6-(benzyloxy)-2-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}oxy)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}acetamide | C54H62N2O11 | 详情 | 详情 | |
| (XLV) | 56362 | N-{(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-1-propenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}acetamide | C54H62N2O11 | 详情 | 详情 | |
| (XLVI) | 56363 | N-{(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-hydroxytetrahydro-2H-pyran-3-yl}oxy)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}acetamide | C51H58N2O11 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XLVI)Alkylation of (XLVI) with (S)-2-chloropropionic acid (XI) provided the lactic acid derivative (XLVII). This was subsequently coupled with the dipeptide amide (XIV), via activation as the mixed anhydride with isobutyl chloroformate, to give the protected disaccharide dipeptide (XLVIII). Finally, hydrogenolysis of the O-benzyl protecting groups of (XLVIII) in the presence of palladium black led to the title compound.
| 【1】 Durette, P.L.; et al.; Synthesis of O-(2-acetamido-2-deoxy-beta-D-glucosyl)-(1--4)-N-acetylmuramoyl-L-alanyl-D-isoglutamine, the repeating disaccharide-dipeptide unit of the bacterial cell-wall peptidoglycan. Carbohydr Res 1979, 77, C1. |
| 【2】 Durette, P.L.; Shen, T.-Y. (Merck & Co., Inc.); Immunologically active peptidyl disaccharides, methods of preparation and vaccine. EP 0018901 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 56332 | (S)-(-)-2-Chloropropionic acid; (S)-2-Chloropropionic acid | 29617-66-1 | C3H5ClO2 | 详情 | 详情 |
| (XIV) | 27130 | benzyl (4R)-5-amino-4-[[(2S)-2-aminopropanoyl]amino]-5-oxopentanoate | C15H21N3O4 | 详情 | 详情 | |
| (XLVI) | 56363 | N-{(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-hydroxytetrahydro-2H-pyran-3-yl}oxy)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-3-yl}acetamide | C51H58N2O11 | 详情 | 详情 | |
| (XLVII) | 56364 | (2R)-2-({(2S,3R,4R,5S,6R)-3-(acetylamino)-5-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-2-(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-4-yl}oxy)propanoic acid | C54H62N2O13 | 详情 | 详情 | |
| (XLVIII) | 56365 | benzyl (4R)-4-[((2S)-2-{[(2R)-2-({(2S,3R,4R,5S,6R)-3-(acetylamino)-5-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-2-(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-4-yl}oxy)propanoyl]amino}propanoyl)amino]-5-amino-5-oxopentanoate | C69H81N5O16 | 详情 | 详情 |