N^α-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine pentafluorophenyl ester | 141462-10-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N^α-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine pentafluorophenyl ester
• 英文别名: (2,3,4,5,6-pentafluorophenyl) (2S,3R)-3-[(2S,3R,4R,5R,6R)-4,5-diacetyloxy-6-(acetyloxymethyl)-3-azidooxan-2-yl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)butanoate
• CAS: 141462-10-4
• 化学式: C₃₇H₃₃F₅N₄O₁₂
• 分子量: 820.681
• InChiKey: UWPFWJBQXFJMMM-BDIDVHOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  58
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  176
• 氢给体数：
  1
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  N^α-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine pentafluorophenyl ester 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 2.5h， 生成 Ac-Pro-Thr-Thr-Thr(α-D-GalNAc)-Pro-Leu-Lys-NH2
  参考文献：
  名称：

  粘蛋白样糖肽的平行固相合成

  摘要：

  摘要糖肽Ac-Pro-Thr（α-d -GalNAc）-Thr（α-d -GalNAc）-Thr（α-d-GalNAc）-Pro-Leu-Lys-NH 2（1）具有三个特征通过固相合成制备了连续的O-糖基化的Thr残基并模拟了一部分粘蛋白2。还合成了七个相关的，部分糖基化的肽（2-8）。这组分子允许对合成方案进行系统分析。Nα-（9-氟烯基甲氧羰基）-O-（3,4,6-三-O-乙酰基-2-叠氮基-2-脱氧-α-d-吡喃半乳糖基）-1-苏氨酸五氟苯基酯[Fmoc-1-Thr （Ac 3-α-d -GalN 3）-OPfp]被用作构建基，当以相对较低的摩尔过量（约1.5当量）使用N，N-二甲基甲酰胺（DMF）作为化合物时，可以有效地偶联。溶剂。为了将叠氮基团转化为N-乙酰基官能团，与用二硫苏糖醇（DTT）还原然后进行N-乙酰化的两步程序相比，用硫代乙酸直接处理更为可取。通过在甲醇中的甲醇钠（10-15

  DOI：

  10.1016/j.carres.2005.05.023
• 作为产物：
  描述：

  3,4,6-tri-O-acetyl-2-azido-2-deoxy-D-galactopyranosyl nitrate 在 四乙基氯化铵 、 silver perchlorate 、 silver carbonate 、 lithium bromide 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 81.5h， 生成 N^α-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine pentafluorophenyl ester
  参考文献：
  名称：

  Syntheses of TN building blocks Nα-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-d-galactopyranosyl)-l-serine/l-threonine pentafluorophenyl esters: comparison of protocols and elucidation of side reactions

  摘要：

  T-N antigen building blocks N-alpha-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl)-L-serine/L-threonine pentafluorophenyl ester [Fmoc-L-Ser/L-Thr(Ac-3-alpha-D-GalN(3))-OPfP, 13/14] have been synthesized by two different routes, which have been compared. Overall isolated yields [three or four chemical steps, and minimal intermediary purification steps] of enantiopure 13 and 14 were 5-18% and 6-10%, respectively, based on 3,4,6-tri-O-acetyl-D-galactal (1). A byproduct of the initial azidonitration reaction of the synthetic sequence, that is, N-acetyl-3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosylamine (5), has been characterized by X-ray crystallography, and shown by H-1 NMR spectroscopy to form complexes with lithium bromide, lithium iodide, or sodium iodide in acetonitrile-d(3). Intermediates 3,4,6-tri-O-acetyl-2-azido2-deoxy-alpha-D-galactopyranosyl bromide (6) and 3,4,6-tri-O-acetyl-2-azido-2-deoxy-beta-D-galactopyranosyl chloride (7) were used to glycosylate N-alpha-(9-fluorenylmethoxycarbonyl)-L-serine/L-threonine pentafluorophenyl esters [Fmoc-L-Ser/L-Thr-OPfp, 11/12]. Previously undescribed low-level dehydration side reactions were observed at this stage; the unwanted byproducts were easily removed by column chromatography. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2005.02.029

文献信息

• Versatile solid-phase thiolytic reduction of azido and N-Dts groups in the synthesis of haemoglobin (67–76) O-glycopeptides and photoaffinity labelled analogues to study glycan T-cell specificity
  作者：Ernst Meinjohanns、Morten Meldal、Teis Jensen、Ole Werdelin、Luisa Galli-Stampino、Søren Mouritsen、Klaus Bock

  DOI：10.1039/a606725e

  日期：——

  A series of O-glycosylated peptides and photoaffinity labelled glycopeptide analogues of the mouse haemoglobin-derived decapeptide Hb (67–76), VITAFNEGLK, which binds well to the MHC class II Ek molecule and is non-immunogenic in CBA/J mice, was synthesized by multiple-column peptide synthesis employing the glycosylated building blocks 1–4 and 7–21. The non-immunogenic peptide VITAFNEGLK was converted into an immunogen by introducing different tumour-associated carbohydrate moieties [β-D-GlcNAc-O -Ser/Thr, α-D-GalNAc-O-Ser/Thr (TN-antigen) core 1 (T-antigen), core 2, core 3 and core 4] to the central position Asn-72 in the decapeptide. Previous studies suggest that T cells may be capable of recognizing epitopes which are partially defined by glycans and may be in direct contact with the T-cell receptor. In order to study the specificity of glycan interactions with the T-cell receptor a series of corresponding glycopeptides labelled with 2-azidobenzamide on the carbohydrate amino function was synthesized. The glycan structure was varied with respect to O-GlcNAc, T and TN-antigen moieties and anomeric configuration. Throughout, efficient reduction of the N-dithiasuccinyl- and azido-functionality-containing building blocks 1, 2, 7, 8, 11, 12, 13, 16, 18 and 20 could be achieved either (i) in solution by utilizing simultaneous in situ reduction with Zn in THF–HOAc–Ac2O or (ii) on solid-phase upon treatment with diisopropylethylamine and an excess of dithiothreitol or α-mercapto-N-methylacetamide. N-Acetylation of the resin-bound glycopeptides furnished the O-glycopeptides 24, 25 and 31–36. No further modification of the carbohydrate moiety on the solid phase was required when utilizing the N-acetylated building blocks 3, 4, 9, 10, 14, 15, 17, 19 and 21. In addition, comparative studies with solid-phase reduction were conducted for the syntheses of the O-linked glycopeptides 24, 25 and 31–36 by employing any of the building blocks 1–4 and 7–21. The photoaffinity labelled glycopeptides 39–45 were synthesized by employing building blocks 1, 2, 7, 8 and 11–13 by reduction of azido or N-Dts functionalities by thiolysis with dithiothreitol and subsequent coupling of the activated photoaffinity label 38 to the glycanamino group of the resin-bound glycopeptides. The synthesized mucin O-glycopeptides 24, 25 and 31–36 and the photoaffinity labelled analogues 39–45 were fully characterized by 1D and 2D 1H NMR spectroscopy and by electrospray mass spectrometry.

  利用糖基化结构单元 1â4 和 7â21 通过多柱肽合成法合成了一系列 O-糖基化肽和光亲和标记的小鼠血红蛋白衍生十肽 Hb（67â76）的糖肽类似物 VITAFNEGLK，它能很好地与 MHC II 类 Ek 分子结合，并且对 CBA/J 小鼠无免疫原性。通过在十肽的中心位置 Asn-72 引入不同的肿瘤相关碳水化合物分子 [δ-D-GlcNAc-O-Ser/Thr、δ-D-GalNAc-O-Ser/Thr（TN 抗原）核心 1（T 抗原）、核心 2、核心 3 和核心 4]，将非免疫原性肽 VITAFNEGLK 转化为免疫原。 以往的研究表明，T 细胞可能能够识别部分由聚糖定义的表位，并可能与 T 细胞受体直接接触。为了研究聚糖与 T 细胞受体相互作用的特异性，我们合成了一系列在碳水化合物氨基功能上用 2- 叠氮苯甲酰胺标记的相应聚糖肽。聚糖结构随 O-GlcNAc、T 和 TN 抗原分子以及异构体构型的不同而变化。自始至终，含 N-二硫代丁二酰基和叠氮官能团的结构单元 1、2、7、8、11、12、13、16、18 和 20 都可以通过以下两种方法实现高效还原：(i) 在溶液中用 Zn 在 THFâHOAcâAc2O 中同时原位还原；或 (ii) 在固相上用二异丙基乙胺和过量的二硫苏糖醇或δ-巯基-N-甲基乙酰胺处理。对树脂结合的糖肽进行 N-乙酰化，可得到 O-糖肽 24、25 和 31â36。在使用 N-乙酰化结构单元 3、4、9、10、14、15、17、19 和 21 时，不需要在固相上进一步修饰碳水化合物分子。此外，在合成 O-连接糖肽 24、25 和 31â36 时，还进行了固相还原比较研究，采用的是 1â4 和 7â21 中的任何一种构建模块。光亲和标记的糖肽 39â45 是通过使用构建模块 1、2、7、8 和 11â13 合成的，方法是用二硫苏糖醇进行硫醇分解还原叠氮或 N-Dts 官能，然后将活化的光亲和标记 38 与树脂结合的糖肽的甘氨酸基偶联。通过一维和二维 1H NMR 光谱以及电喷雾质谱法，对合成的粘蛋白 O 型糖肽 24、25 和 31â36 以及光亲和标记的类似物 39â45 进行了全面鉴定。
• Synthesis of the glycosyl amino acids Nα-Fmoc-Ser[Ac4-β-d-Gal p-(1 → 3)-Ac2-α-d-GalN3 p]-OPfp and Nα-Fmoc-Thr[Ac4-β-d-Gal p-(1 → 3)-Ac2-α-d-GalN3 p]-OPfp and the application in the solid-phase peptide synthesis of multiply glycosylated mucin peptides with Tn and T antigenic structures
  作者：Hans Paulsen、Stefan Peters、Tim Bielfeldt、Morten Meldal、Klaus Bock

  DOI：10.1016/0008-6215(94)00292-n

  日期：1995.3

  -β- d -Gal p-(1 → 3)- Ac 2 -α- d -GalN 3 p]- OPfp and N α - Fmoc-Thr[Ac 4 -β- d -Gal p-(1 → 3)- Ac 2 -α- d -GalN 3 p]- OPfp were synthesized. Glycosylation of Nα-Fmoc-Ser-OPfp or Nα-Fmoc-Thr-OPfp with protected β- d -Gal -(1 → 3)- d -GalN 3 donors afforded the glycosyl amino acids containing an activated C-terminus which could be utilized directly for solid-phase glycopeptide synthesis. The transformation

  摘要两个新的糖基氨基酸Nα-Fmoc-Ser [Ac 4-β-d -Gal p-（1→3）-Ac 2-α-d -GalN 3 p]-OPfp和Nα-Fmoc-Thr [合成了Ac 4-β-d -Gal p-（1→3）-Ac 2-α-d -GalN 3 p] -OPfp。Nα-Fmoc-Ser-OPfp或Nα-Fmoc-Thr-OPfp的糖基化与受保护的β-d -Gal-（1→3）-d -GalN 3供体进行糖基化，得到的糖基氨基酸含有一个活化的C末端，可以是直接用于固相糖肽合成。在合成结束时，通过用硫代乙酸处理与聚合物结合的糖肽，可以定量实现2-叠氮基向乙酰氨基衍生物的转化。八种三糖基化粘蛋白肽的组装证明了该策略的多功能性，这些肽是通过多柱技术同时合成的。
• Solid phase peptide synthesis of mucin glycopeptides
  作者：S. Peters、T. Bielfeldt、M. Meldal、K. Bock、H. Paulsen

  DOI：10.1016/s0040-4039(00)79011-3

  日期：1992.10

  The synthesis of the new glycosylamino acid building block Nα-Fmoc-Thr(Ac4-β-D-Galp)-(1→3)-(Ac2-α-D-GalpN3)-OPfp 3 and its use in a solid phase synthesis of triple glycosylated peptides from human intestinal mucin is described. The azide reduction was performed with thioacetic acid on the polymere bound glycopeptides.

  新glycosylamino酸构建块N的合成α -Fmoc-THR（AC 4（1→3） - - （AC-β-d-高浦）2 -α-d-GalpN 3）-OPfp 3和它的使用在描述了从人肠粘蛋白的三糖基化肽的固相合成。用硫代乙酸对聚合物结合的糖肽进行叠氮化物还原。
• Synthesis and characterisation of highly glycosylated glycopeptides with Tn-antigenic structures corresponding to human glycophorin AN
  作者：Gunther Klich、Hans Paulsen、Bernd Meyer、Morten Meldal、Klaus Bock

  DOI：10.1016/s0008-6215(96)00337-0

  日期：1997.3

  Two highly glycosylated O-glycopeptides corresponding to human glycophorin AN with Tn-antigenic structures were synthesised. The first glycopeptide has two glycosylated clusters with three and six adjacent 2-acetamido-2-deoxy-D-galactose (GalNAc) glycosylation sites and represents the N-terminal octadecapeptide from Leu-1 to Lys-18. The second glycopeptide, a decapeptide from His-9 to Lys-18, contains

  合成了两个具有人糖蛋白AN的具有Tn抗原结构的高度糖基化的O-糖肽。第一糖肽具有两个具有三个和六个相邻的2-乙酰氨基-2-脱氧-D-半乳糖（GalNAc）糖基化位点的糖基化簇，并且代表从Leu-1至Lys-18的N-末端八肽。第二个糖肽，即从His-9到Lys-18的十肽，包含6个相邻的GalNAc糖基化位点作为紧密簇。通过使用含碳水化合物的结构单元Fmoc-Ser（Ac3GalN3）-Pfp和Fmoc-Thr（Ac3GalN3）-Pfp实现固相合成。合成的物质通过NMR光谱技术表征。使用的主要技术是同核TOCSY和NOESY以及用于13C，1H相关性的HMQC和HMBC。
• Paulsen, Hans; Bielfeldt, Tim; Peters, Stefan, Liebigs Annalen der Chemie, 1994, # 4, p. 369 - 380
  作者：Paulsen, Hans、Bielfeldt, Tim、Peters, Stefan、Meldal, Morten、Bock, Klaus

  DOI：——

  日期：——