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【结 构 式】 
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【分子编号】21969 【品名】(3aR,5R,6R,7R,7aR)-6-(acetoxy)-5-[(acetoxy)methyl]-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]oxazol-7-yl acetate 【CA登记号】 |
【 分 子 式 】C14H19NO8 【 分 子 量 】329.3068 【元素组成】C 51.06% H 5.82% N 4.25% O 38.87% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)Glycosylation of the protected glucosamine (XXVI) with the glucopyranooxazoline (XXVII) was effected in the presence of p-toluenesulfonic acid in dichloroethane to give the protected chitobioside derivative (XXVIII). Methanolysis of the acetate esters of (XXVIII), followed by protection of the resultant triol (XXIX) with acetone dimethylacetal, gave rise to the 4',6'-isopropylidene derivative (XXX). The 3'-hydroxyl group of (XXX) was then protected as the benzyl ether (XXXI) with benzyl bromide in the presence of Ba(OH)2 and BaO. Removal of the 2-butenyl group of (XXXI) to furnish (XXXII) was performed by means of potassium tert-butoxide in hot DMSO. Subsequent alkylation of (XXXII) with (S)-2-chloropropionic acid (XI) led to acid (XXXIII).
| 【1】 Kiso, M.; et al.; A general, convenient synthesis of the repeating, disaccharide-dipeptide unit of the bacterial, cell-wall peptidoglycan by the oxazoline method. Carbohydr Res 1980, 83, 1, C8. |
| 【2】 Kiso, M.; et al.; Synthesis and immunoadjuvant activities of the repeating, disaccharide-dipeptide unit of the bacterial, cell-wall peptidoglycan and of some carbohydrate analogs. Carbohydr Res 1982, 104, 2, 253. |
| 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 |
| (XXVI) | 56344 | N-{(2S,3R,4R,5S,6R)-2-(benzyloxy)-6-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]-5-hydroxytetrahydro-2H-pyran-3-yl}acetamide | C26H33NO6 | 详情 | 详情 | |
| (XXVII) | 21969 | (3aR,5R,6R,7R,7aR)-6-(acetoxy)-5-[(acetoxy)methyl]-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]oxazol-7-yl acetate | C14H19NO8 | 详情 | 详情 | |
| (XXVIII) | 56345 | (2R,3R,4R,5R,6R)-3-(acetylamino)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-5-(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-4-yl acetate | C40H52N2O14 | 详情 | 详情 | |
| (XXIX) | 56346 | N-[(2S,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]acetamide | C34H46N2O11 | 详情 | 详情 | |
| (XXX) | 56347 | N-[(4aR,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-8-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]acetamide | C37H50N2O11 | 详情 | 详情 | |
| (XXXI) | 56348 | N-[(4aR,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-[(E)-2-butenyloxy]tetrahydro-2H-pyran-3-yl}oxy)-8-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]acetamide | C44H56N2O11 | 详情 | 详情 | |
| (XXXII) | 56349 | N-[(4aR,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]-4-hydroxytetrahydro-2H-pyran-3-yl}oxy)-8-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]acetamide | C40H50N2O11 | 详情 | 详情 | |
| (XXXIII) | 56350 | (2R)-2-({(2R,3S,4R,5R,6S)-3-{[(4aR,6R,7R,8R,8aS)-7-(acetylamino)-8-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy}-5-(acetylamino)-6-(benzyloxy)-2-[(benzyloxy)methyl]tetrahydro-2H-pyran-4-yl}oxy)propanoic acid | C43H54N2O13 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Chlorination and acetylation of N-acetyl glucosamine (I) with acetyl chloride afforded intermediate (II), which was cyclized to the oxazoline (III) with NaHCO3 and tetraethylammonium chloride. Opening of this heterocycle by treatment with 3-pentanol (IV) in the presence of p-toluenesulfonic acid yielded the b-glucoside (V). The primary hydroxyl group of (V) was subsequently deprotected by the following sequence, consisting of hydrolysis of the acetate esters with NaOMe in MeOH to give triol (VI), followed by protection of the primary alcohol as the trityl ether (VIII), acetylation of the secondary alcohols of (VIII), and finally deprotection of the trityl group with aqueous AcOH giving finally (X). Swern oxidation of the resulting primary alcohol (X) using DMSO and SO3-pyridine produced aldehyde (XI).
| 【1】 Smith, P.W.; Robinson, J.E.; Evans, D.N.; Sollis, S.L.; Trivedi, N.; Bethell, R.C.; Howes, P.D.; Sialidase inhibitors related to zanamivir: Synthesis and biological evaluation of 4H-pyran 6-ether and ketone. Bioorg Med Chem Lett 1999, 9, 4, 601. |
| 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) | 21967 | N-[(2S,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]acetamide | C8H15NO6 | 详情 | 详情 | |
| (II) | 21968 | (2R,3R,4R,5S,6R)-3-(acetamido)-5-(acetoxy)-6-[(acetoxy)methyl]-2-chlorotetrahydro-2H-pyran-4-yl acetate | 3068-34-6 | C14H20ClNO8 | 详情 | 详情 |
| (III) | 21969 | (3aR,5R,6R,7R,7aR)-6-(acetoxy)-5-[(acetoxy)methyl]-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d][1,3]oxazol-7-yl acetate | C14H19NO8 | 详情 | 详情 | |
| (IV) | 21970 | 3-pentanol | 584-02-1 | C5H12O | 详情 | 详情 |
| (V) | 21971 | (2R,3R,4R,5R,6R)-3-(acetamido)-5-(acetoxy)-6-[(acetoxy)methyl]-2-(1-ethylpropoxy)tetrahydro-2H-pyran-4-yl acetate | C19H31NO9 | 详情 | 详情 | |
| (VI) | 21972 | N-[(2R,3R,4R,5S,6R)-2-(1-ethylpropoxy)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]acetamide | C13H25NO6 | 详情 | 详情 | |
| (VII) | 21973 | 1-[chloro[bis(4-methoxyphenyl)]methyl]-4-methoxybenzene; 4-[chloro[bis(4-methoxyphenyl)]methyl]phenyl methyl ether | 49757-42-8 | C22H21ClO3 | 详情 | 详情 |
| (VIII) | 21974 | N-((2R,3R,4R,5S,6R)-2-(1-ethylpropoxy)-4,5-dihydroxy-6-[[tris(4-methoxyphenyl)methoxy]methyl]tetrahydro-2H-pyran-3-yl)acetamide | C35H45NO9 | 详情 | 详情 | |
| (IX) | 21975 | (2R,3R,4R,5R,6R)-3-(acetamido)-5-(acetoxy)-2-(1-ethylpropoxy)-6-[[tris(4-methoxyphenyl)methoxy]methyl]tetrahydro-2H-pyran-4-yl acetate | C39H49NO11 | 详情 | 详情 | |
| (X) | 21976 | (2R,3R,4R,5R,6R)-3-(acetamido)-5-(acetoxy)-2-(1-ethylpropoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl acetate | C17H29NO8 | 详情 | 详情 | |
| (XI) | 21977 | (2R,3R,4R,5R,6S)-3-(acetamido)-5-(acetoxy)-2-(1-ethylpropoxy)-6-formyltetrahydro-2H-pyran-4-yl acetate | C17H27NO8 | 详情 | 详情 |