6-氯-3-吲哚基-β-D-吡喃葡萄糖苷的合成
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摘要
本文首次报道了6-氯-3-吲哚基-β-D-吡喃葡萄糖苷的合成方法。采用卤代糖法,以α-D-吡喃葡萄糖为起始原料制得糖基供体2,3,4,6-四-O-乙酰基-α-D-吡喃葡萄糖溴化物,然后与1-(6-氯-3-羟基-1H-吲哚-1-基)乙-1-酮进行偶联成苷反应得1-O-(N-乙酰基-6-氯-3-吲哚基)-2,3,4,6-四-O-乙酰基-D-葡萄糖苷,最后在甲醇钠/甲醇条件下脱乙酰基得目标化合物,总收率52%。所得目标化合物的HPLC纯度93.2%,HPLC保留时间及熔点均与标准品一致。
The synthesis of 6-chloro-3-indolyl-β-D-glucopyranoside was reported for the first time.In this paper,glucose donor 2,3,4,6-tetra-O-acetyl-a-.D-glucopyranosyl bromide was prepared from a-D-glucopyranose by glycosyl halide method,then it reacted with 1-(6-chloro-3-hydroxy-1 H-indol-l-yl)ethan-l-one to give 1-O-(N-acetyl-6-chloro-3-indolyl)-2,3,4,6-tetra-O-acetyl-D-glucopyranoside,which was followed by a deacetylation in the presence of sodium methoxide/methanol to afford the target compound with a total yield of 52%.The retention time in HPLC and melting point of the obtained target compound(HPLC purity 93.2%)are consistent with the standard product.
The synthesis of 6-chloro-3-indolyl-β-D-glucopyranoside was reported for the first time.In this paper,glucose donor 2,3,4,6-tetra-O-acetyl-a-.D-glucopyranosyl bromide was prepared from a-D-glucopyranose by glycosyl halide method,then it reacted with 1-(6-chloro-3-hydroxy-1 H-indol-l-yl)ethan-l-one to give 1-O-(N-acetyl-6-chloro-3-indolyl)-2,3,4,6-tetra-O-acetyl-D-glucopyranoside,which was followed by a deacetylation in the presence of sodium methoxide/methanol to afford the target compound with a total yield of 52%.The retention time in HPLC and melting point of the obtained target compound(HPLC purity 93.2%)are consistent with the standard product.
引文
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[2]HARGOVIND R,TOSHIHIRO H,KIKUO I,et al.Cardiac glycosydes:5.Stereoselective syntheses of digitoxigenirα-D,β-D,α-L and p-L-glucosides[J].Tetrahedron,1985,41(20):5427-5438.
[3]MATTHIAS B,SEBASTIAN G,NIKLAS L,et al. Welldefined carbohydrate-based polymers in calcium carbonate crystallization:Influence of stereochemistry in the polymer side chain on polymorphism and morphology[J].Eur Polym J,2015,69:628-635.
[4]NIGEL P,RHONA M D,ALAN O B,et al.Synthesis of a glucuronic acid and glucose conjugate library and evaluation of effects on endothelial cell growth[J].Carbohydr Res2004,339:1873-1887.
[5]HUANG S L,ZHU Y L,PAN Y J,et al.Synthesis of arbutin by two-step reaction from glucose[J].J Zhejiang Univ SCI2004,5(12):1509-1511.
[6]吴清平,韦献虎,张菊梅,等.吲哚酚显色底物的合成及其在微生物检测中的应用研究进展[J].化学通报,201376(7):580-589.
[7]RIVAULT F,TRANOY-OPALINSKI I,GESSON J P.A new linker for glucuronylated anticancer prodrugs[J].Bioorg Med Chem,2014,12(4):675-682.
[8]PAUL W N,GARY W.Syntheses of daidzein-7-ylβ-D-glucopyranosiduronic acid and daidzein-4%,7-yl di-β-Dglucopyranosiduronic acid[J].Carbohydr Res,2001,330:511-515.
[9]CHENG T C,ROFFLER S R,TZOU S C,et al.An activitybased near-infrared glucuronide trapping probe for imagingβ-glucuronidase expression in deep tissues[J].J Am Chem Soc,2012,134:3103-3110.
[10]KANEKO S,KITAOKA M,KUNO A,et al.Syntheses of 4-methylumbelliferyl-β-D-xylobioside and 5-bromo-3-indolyl-β-D-xylobioside for sensitive detection of xylanase activity on agar plates[J].Biosci Biotechnol Biochem,2000,64(4):741-745.
[11]UNZUE A,ZHAO H,LOLLI G,et al.The"gatekeeper"residue influences the binding mode of acetyl indoles to bromodomains[J].J Med Chem,2016,59:3087-3097.
[12]ZHAO H W,WEN Y L,FU L L,et al.Synthesis and antitumor activity of 7-azaindirubin[J].Chin Chem Lett,2009,20:542-544.
[13]VO Q V,ROCHFORT S,NAM P C,et al.Synthesis of aromatic and indole alpha-glucosinolates[J]. Carbohydr Res,2018,455:45-53.
[14]HOLGER G,TOBIAS M,MIKE M K B.Novel olefinphosphorus hybrid and diene ligands derived from carbohydrates[J].Synthesis,2010,19:3248-3258.