(2R,3S,4R,5R,6R)-6-((S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanamido)-5-acetamido-2-(acetoxymethyl)tetrahydro-2H-pyran-3,4-diyl diacetate | 154395-61-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 糖脂
• 英文名称: (2R,3S,4R,5R,6R)-6-((S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanamido)-5-acetamido-2-(acetoxymethyl)tetrahydro-2H-pyran-3,4-diyl diacetate
• 英文别名: N^ω-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl-N^α-(9-fluorenylmethyloxycarbonyl))-L-asparagine tert-butyl ester；N-α-fluorenylmethoxycarbonyl-N-γ-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-L-asparagine tert-butyl ester；N-α-fluorenylmethoxycarbonyl-N-β-(2-N-acetylamido-2-deoxy-β-D-glucopyranosyl)-2-tert-butoxy-L-asparagine；tert-butyl (2S)-4-[[(2R,3R,4R,5S,6R)-3-acetamido-4,5-diacetyloxy-6-(acetyloxymethyl)oxan-2-yl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxobutanoate
• CAS: 154395-61-6
• 化学式: C₃₇H₄₅N₃O₁₃
• 分子量: 739.777
• InChiKey: LCBFPOZEMMSKAF-GBBYZUMQSA-N

物化性质

• 沸点：
  918.2±65.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  53
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  211
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (2R,3S,4R,5R,6R)-6-((S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanamido)-5-acetamido-2-(acetoxymethyl)tetrahydro-2H-pyran-3,4-diyl diacetate 在 N,N-二异丙基乙胺 、 fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 生成
  参考文献：
  名称：

  Amino acid fluoride for glycopeptide synthesis

  摘要：

  The formation of N-glycosidic linkage between N-acetylglucosamine (GlcNAc) and asparagine (Asn) was effected using aspartic acid gamma-fluoride in combination with either glycosyl azide or silyl carbamate, by the action of Lindlar catalyst or Bu4NF Further elongation of peptide chain was performed to give pentapeptide. This method was further applied into the synthesis of trisaccharidic asparagine, using beta-methoxybenzyl assisted stereoselective B-mannosylation as the key transformation. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)02228-5
• 作为产物：
  描述：

  [(2R,3S,4R,5R,6R)-5-acetamido-3,4-diacetyloxy-6-[(2-methylpropan-2-yl)oxycarbonylamino]oxan-2-yl]methyl acetate 在 2,6-二叔丁基-4-甲基吡啶 、 四丁基氟化铵 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 生成 (2R,3S,4R,5R,6R)-6-((S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanamido)-5-acetamido-2-(acetoxymethyl)tetrahydro-2H-pyran-3,4-diyl diacetate
  参考文献：
  名称：

  Amino acid fluoride for glycopeptide synthesis

  摘要：

  The formation of N-glycosidic linkage between N-acetylglucosamine (GlcNAc) and asparagine (Asn) was effected using aspartic acid gamma-fluoride in combination with either glycosyl azide or silyl carbamate, by the action of Lindlar catalyst or Bu4NF Further elongation of peptide chain was performed to give pentapeptide. This method was further applied into the synthesis of trisaccharidic asparagine, using beta-methoxybenzyl assisted stereoselective B-mannosylation as the key transformation. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)02228-5

文献信息

• Site-Selective Chemoenzymatic Glycosylation of an HIV-1 Polypeptide Antigen with Two Distinct N-Glycans via an Orthogonal Protecting Group Strategy
  作者：Christian Toonstra、Mohammed N. Amin、Lai-Xi Wang

  DOI：10.1021/acs.joc.6b01044

  日期：2016.8.5

  glycosynthase-catalyzed transglycosylation reactions. It was observed that the protecting groups on one neighboring GlcNAc moiety have an impact on the substrate activity of another GlcNAc acceptor toward some endoglycosynthases in transglycosylation. The usefulness of this synthetic strategy was exemplified by an efficient synthesis of the glycopeptide neutralizing epitope of broadly HIV-neutralizing antibody

  描述了用于在多肽中顺序安装不同N-聚糖的会聚化学酶法。该方法包括在自动固相肽合成（SPPS）期间引入区别保护的GlcNAc-Asn构建基块，然后通过糖合酶催化的转糖基化反应对GlcNAc引物进行正交脱保护，并进行糖链的位点选择性顺序延伸。观察到一个相邻的GlcNAc部分上的保护基在转糖基化中对另一种GlcNAc受体对某些内切糖合酶的底物活性有影响。有效合成广泛中和HIV的抗体PG9的糖肽中和表位证明了这种合成策略的实用性。
• Improving Selectivity, Proteolytic Stability, and Antitumor Activity of Hymenochirin-1B: A Novel Glycosylated Staple Strategy
  作者：Yulei Li、Yihan Zhang、Minghao Wu、Qi Chang、Honggang Hu、Xia Zhao

  DOI：10.1021/acschembio.9b00046

  日期：2019.3.15

  glycosylation strategy. Some analogues showed improvement not only in selectivity and proteolytic stability but also in antitumor activity. Among them, the glycosylated stapled peptide H-58 was identified as the most potential antitumor peptide. Flow cytometry and a competitive binding assay revealed that H-58 displayed significant antitumor selectivity. Confocal microscopy and nuclear staining with Hoechst

  作为宿主防御肽，hymenochirin-1B因其强大的细胞毒活性而受到越来越多的关注。但是，其差的选择性和蛋白水解稳定性仍然是临床应用的主要障碍。为了解决这些问题，我们基于阳离子残基取代和装订结合糖基化策略设计并合成了膜联膜蛋白-1B的一系列肽类似物。一些类似物不仅显示出选择性和蛋白水解稳定性的改善，而且还显示出抗肿瘤活性的改善。其中，糖基化固定肽H-58被鉴定为最有潜力的抗肿瘤肽。流式细胞仪和竞争性结合试验表明，H-58表现出显着的抗肿瘤选择性。共焦显微镜检查和Hoechst染料的核染色表明，H-58进入细胞核并造成DNA损伤。总之，糖基化钉书钉肽的策略是一种有前途的方法，用于提高膜球蛋白-1B的抗肿瘤选择性，蛋白水解稳定性和抗肿瘤活性，该膜可用于其他生物活性肽修饰。
• Novel sequential solid-phase synthesis of N-linked glycopeptides from natural sources
  作者：Ernst Meinjohanns、Morten Meldal、Hans Paulsen、Raymond A. Dwek、Klaus Bock

  DOI：10.1039/a705528e

  日期：——

  In the present report a practical and versatile procedure for the solid-phase synthesis of N-linked glycopeptides from natural sources has been demonstrated. The approach is based on the mild hydrazinolysis procedure to release N-linked oligosaccharides in their intact unreduced form from the natural glycoproteins, e.g. fetuin and ribonuclease B and subsequent formation of the corresponding glycosylamines. Treatment of the reducing sugars 1–7 with a saturated solution of ammonium hydrogen carbonate in either water or dimethyl sulfoxide (DMSO) gives in almost quantitative yields the glycosylamines 8–14. Coupling of the unprotected glycosylamines 8–14 to the side-chain-activated aspartic acid derivative Fmoc-Asp(ODhbt)-OBut 16 affords the N-glycosylated asparagine derivatives 17–23. Subsequent acetylation of the carbohydrate hydroxy groups and cleavage of the tert-Bu ester by trifluoroacetic acid (TFA) treatment yields the glycosylated N-linked building blocks 31–37. The building blocks 31–37 are then incorporated into the multiple-column peptide-synthesis protocol of the glycopeptide T-cell epitope analogues 40–46 of the mouse haemoglobin-derived decapeptide Hb (67–76), VITAFNEGLK. The decapeptide sequence VITAFNEGLK binds well to the MHC Class II Ek molecule and is non-immunogenic in CBA/J mice. Syntheses of several natural and unnatural glycosylations, e.g. N-acetylglucosamine, N,N′-diacetylchitobiose, glucose, maltotriose, maltoheptose and di- and tri-antennary complex oligosaccharides on the decapeptide Hb (67–76) affording the N-linked glycopeptides 40–46 are described. The N-linked glycopeptides 40–46 have been fully characterised by 1D- and 2D-1H and 13C NMR spectroscopy and by ES-MS.

  本报告展示了一种从天然来源固相合成 N-连接糖肽的实用且多功能的方法。该方法基于温和的肼解程序，以完整的未还原形式从天然糖蛋白（如胎盘素和核糖核酸酶 B）中释放出 N-连接寡糖，随后形成相应的糖基胺。用碳酸氢铵在水或二甲基亚砜（DMSO）中的饱和溶液处理还原糖 1-7，几乎可以得到定量的糖基胺 8-14。将未受保护的糖基胺 8-14 与侧链激活的天冬氨酸衍生物 Fmoc-Asp(ODhbt)-OBut 16 偶联，可得到 N-糖基化的天冬酰胺衍生物 17-23。随后通过三氟乙酸（TFA）处理对碳水化合物羟基进行乙酰化并裂解叔丁酯，可得到糖基化的 N-连接构筑模块 31-37。然后，将这些结构单元 31-37 加入小鼠血红蛋白衍生的十肽 Hb（67-76）VITAFNEGLK 的糖肽 T 细胞表位类似物 40-46 的多柱肽合成方案中。十肽序列 VITAFNEGLK 与 MHC II 类 Ek 分子结合良好，对 CBA/J 小鼠无免疫原性。本文介绍了在十肽 Hb（67-76）上进行几种天然和非天然糖基化，如 N-乙酰葡糖胺、N,N′-二乙酰壳寡糖、葡萄糖、麦芽三糖、麦芽庚糖以及二元和三元泛酰复合寡糖，从而得到 N-连接的糖肽 40-46。通过 1D- 和 2D-1H 和 13C NMR 光谱以及 ES-MS 对 N-连接的糖肽 40-46 进行了全面鉴定。
• Native N-glycopeptide thioester synthesis through N→S acyl transfer
  作者：Bhavesh Premdjee、Anna L. Adams、Derek Macmillan

  DOI：10.1016/j.bmcl.2011.05.059

  日期：2011.9

  Peptide thioesters are important tools for the total synthesis of proteins using native chemical ligation (NCL). Preparation of glycopeptide thioesters, that enable the assembly of homogeneously glycosylated proteins, is complicated by the perceived fragile nature of the sugar moiety. Herein, we demonstrate the compatibility of thioester formation via N→S acyl transfer with native N-glycopeptides and

  肽硫酯是使用天然化学连接 (NCL) 进行蛋白质全合成的重要工具。糖肽硫酯的制备能够组装均匀的糖基化蛋白质，但由于糖部分的脆弱性质而变得复杂。在此，我们证明了通过N → S酰基转移形成的硫酯与天然N-糖肽的相容性，并报告了有助于其制备的观察结果。
• A Simple Method for the Synthesis of Nβ-Glycosylated-Asparagine and -Glutamine Derivatives
  作者：Mamoru Mizuno、Ikuyo Muramoto、Katsuaki Kobayashi、Hiroshi Yaginuma、Toshiyuki Inazu

  DOI：10.1055/s-1999-3674

  日期：——

  N β-Glycosylated-asparagine and -glutamine derivatives, which are useful precursors for the synthesis of N-glucopeptides and their analogs, were obtained in good yields by the reaction of a glycosyl azide and an N α-protected-aspartic/glutamic acid α-monoester in the presence of trialkylphosphine at low temperature.

  在三烷基膦存在下，通过糖基叠氮化物与 N δ-保护-天冬氨酸/谷氨酸 δ-单酯在低温下的反应，获得了 N δ-糖基化-天冬酰胺和-谷氨酰胺衍生物，这些衍生物是合成 N-葡肽及其类似物的有用前体，产量很高。