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【结 构 式】 
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【分子编号】56331 【品名】N-{(1R,2R,3S)-3-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-1-(diethoxymethyl)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxypropyl}acetamide 【CA登记号】 |
【 分 子 式 】C44H60N2O12 【 分 子 量 】808.96668 【元素组成】C 65.33% H 7.48% N 3.46% O 23.73% |
合成路线1
该中间体在本合成路线中的序号：(X)Acylation of 3,4,6-tri-O-benzyl-D-glucosamine (I) by means of pentachlorophenyl dichloroacetate (II) yielded the dichloroacetamide (III). Acylation of glucosamine (III) with acid chloride (IV) in pyridine/CH2Cl2 provided the 1-O-p-nitrobenzoyl derivative (V), which was treated with hydrogen bromide in CH2Cl2 to furnish glycosyl bromide (VI). Coupling of bromide (VI) with the glucosamine cyclic carbamate (VII) was performed in the presence of mercury(II) cyanide to afford the disaccharide (VIII). Alkaline hydrolysis of the dichloroacetamide and cyclic carbamate functions of (VIII) gave diamine (IX), which was subsequently acetylated to diamide (X) by means of acetic anhydride in pyridine.
| 【1】 Kusumoto, S.; et al.; Chemical synthesis and biological activities of two disaccharide dipeptides corresponding to the repeating units of bacterial peptidoglycan. Bull Chem Soc Jpn 1986, 59, 5, 1411. |
| 【2】 Kusumoto, S.; et al.; Synthesis of N-acetyl-beta-D-glucosaminyl-(1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine. Tetrahedron Lett 1978, 45, 4407. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 56323 | (3R,4R,5S,6R)-3-amino-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-ol | C27H31NO5 | 详情 | 详情 | |
| (II) | 56324 | Pentachlorophenyl dichloroacetate | 19745-69-8 | C8HCl7O2 | 详情 | 详情 |
| (III) | 56325 | N-{(3R,4R,5S,6R)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]-2-hydroxytetrahydro-2H-pyran-3-yl}-2,2-dichloroacetamide | C29H31Cl2NO6 | 详情 | 详情 | |
| (IV) | 18941 | p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride | 122-04-3 | C7H4ClNO3 | 详情 | 详情 |
| (V) | 56326 | (3R,4R,5S,6R)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]-3-[(2,2-dichloroacetyl)amino]tetrahydro-2H-pyran-2-yl 4-nitrobenzoate | C36H34Cl2N2O9 | 详情 | 详情 | |
| (VI) | 56327 | N-{(3R,4R,5S,6R)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]-2-bromotetrahydro-2H-pyran-3-yl}-2,2-dichloroacetamide | C29H30BrCl2NO5 | 详情 | 详情 | |
| (VII) | 56328 | (4R,5R)-4-(diethoxymethyl)-5-[(R)-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl](hydroxy)methyl]-1,3-oxazolidin-2-one | C43H54Cl2N2O12 | 详情 | 详情 | |
| (VIII) | 56329 | N-[(2S,3R,4R,5S,6R)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]-2-({(R)-[(4R,5R)-4-(diethoxymethyl)-2-oxo-1,3-oxazolidin-5-yl][(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}oxy)tetrahydro-2H-pyran-3-yl]-2,2-dichloroacetamide | C43H54Cl2N2O12 | 详情 | 详情 | |
| (IX) | 56330 | (1S,2R,3R)-3-amino-1-({(2S,3R,4R,5S,6R)-3-amino-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-4,4-diethoxy-2-butanol | C40H56N2O10 | 详情 | 详情 | |
| (X) | 56331 | N-{(1R,2R,3S)-3-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-1-(diethoxymethyl)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxypropyl}acetamide | C44H60N2O12 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)Alkylation of the sodium alkoxide of (X) with (S)-2-chloropropionic acid (XI), followed by esterification with diazomethane provided the methyl ester adduct (XII). Alkaline hydrolysis of ester (XII) with KOH yielded carboxylic acid (XIII), which was coupled with the dipeptide amide (XIV) to give the protected disaccharide dipeptide (XV). Subsequent acidic hydrolysis of the ketal functions of (XV) proceeded with concomitant cyclization to the pyranose form (XVI). The O-benzyl protecting groups of (XVI) were finally removed by catalytic hydrogenolysis in the presence of palladium black.
| 【1】 Kusumoto, S.; et al.; Synthesis of N-acetyl-beta-D-glucosaminyl-(1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine. Tetrahedron Lett 1978, 45, 4407. |
| 【2】 Kusumoto, S.; et al.; Chemical synthesis and biological activities of two disaccharide dipeptides corresponding to the repeating units of bacterial peptidoglycan. Bull Chem Soc Jpn 1986, 59, 5, 1411. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 56331 | N-{(1R,2R,3S)-3-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)-1-(diethoxymethyl)-3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxypropyl}acetamide | C44H60N2O12 | 详情 | 详情 | |
| (XI) | 56332 | (S)-(-)-2-Chloropropionic acid; (S)-2-Chloropropionic acid | 29617-66-1 | C3H5ClO2 | 详情 | 详情 |
| (XII) | 56333 | methyl (2R)-2-[((1R,2R)-2-(acetylamino)-1-{(S)-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3,3-diethoxypropyl)oxy]propanoate | C48H66N2O14 | 详情 | 详情 | |
| (XIII) | 56334 | (2R)-2-[((1R,2R)-2-(acetylamino)-1-{(S)-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3,3-diethoxypropyl)oxy]propanoic acid | C47H64N2O14 | 详情 | 详情 | |
| (XIV) | 27130 | benzyl (4R)-5-amino-4-[[(2S)-2-aminopropanoyl]amino]-5-oxopentanoate | C15H21N3O4 | 详情 | 详情 | |
| (XV) | 56335 | benzyl (5R,6R,8R,11S,14R)-5-(acetylamino)-6-{(S)-({(2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl}oxy)[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-14-(aminocarbonyl)-4-ethoxy-8,11-dimethyl-9,12-dioxo-3,7-dioxa-10,13-diazaheptadecan-17-oate | C62H83N5O17 | 详情 | 详情 | |
| (XVI) | 56336 | 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-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]oxy}propanoyl)amino]propanoyl}amino)-5-amino-5-oxopentanoate | C55H69N5O16 | 详情 | 详情 |