(5R)-N^α-(fluoren-9-ylmethoxycarbonyl)-N^ε-benzyloxycarbonyl-5-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-5-hydroxy-L-lysine | 270089-67-3

• 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: (5R)-N^α-(fluoren-9-ylmethoxycarbonyl)-N^ε-benzyloxycarbonyl-5-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-5-hydroxy-L-lysine
• 英文别名: (5R)-N^α-(fluoren-9-ylmethoxycarbonyl)-N^ε-benzyloxycarbonyl-5-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopranosyl)-5-hydroxy-L-lysine；(2S,5R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-6-(phenylmethoxycarbonylamino)-5-[(2R,3R,4S,5S,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyhexanoic acid
• CAS: 270089-67-3
• 化学式: C₄₃H₄₈N₂O₁₆
• 分子量: 848.858
• InChiKey: DVXGMJMXTAIYBC-CKOIINKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  61
• 可旋转键数：
  24
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  238
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  {tert-butoxycarbonyl-[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propyl]amino}acetic acid 、 Fmoc-L-苯丙氨酸 、 Boc-Gly-Ile-OH 、 (5R)-N^α-(fluoren-9-ylmethoxycarbonyl)-N^ε-benzyloxycarbonyl-5-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-5-hydroxy-L-lysine 、 alkaline earth salt of/the/ methylsulfuric acid 以19.5 mg的产率得到
  参考文献：
  名称：

  Probing Molecular Interactions within Class II MHC A^q/Glycopeptide/T-Cell Receptor Complexes Associated with Collagen-Induced Arthritis

  摘要：

  T cells obtained in a mouse model for rheumatoid arthritis are activated by a glycopeptide fragment from rat type II collagen (CII) bound to the class II major histocompatibility complex A(q) molecule. We report a comparative model of A(q) in complex with the glycopeptide CII260-267. This model was used in a structure-based design approach where the amide bond between Ala(261) and Gly(262) in the glycopeptide was selected for replacement with psi[COCH2], psi[CH2NH2+], and psi[(E)-CH=CH] isosteres. Ala-Gly isostere building blocks were then synthesized and introduced in CII260-267 and CII259-273 glycopeptides. The modified glycopeptides were evaluated for binding to the A(q) molecule, and the results were interpreted in view of the A(q)/glycopeptide model. Moreover, recognition by a panel of T-cell hybridomas revealed high sensitivity for the backbone modifications. These studies contribute to the understanding of the interactions in the ternary A(q)/glycopeptide/T-cell receptor complexes that activate T cells in autoimmune arthritis and suggest possibilities for new vaccination approaches.

  DOI：

  10.1021/jm0705410
• 作为产物：
  描述：

  (2S,5R)-2,6-Diamino-5-hydroxy-hexanoic acid 9-bora-bicyclo[3.3.1]non-9-yl ester 在 甲醇 、 silver silicate 、 3 A molecular sieve 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 氯仿 、 水 、 丙酮 为溶剂， 反应 30.0h， 生成 (5R)-N^α-(fluoren-9-ylmethoxycarbonyl)-N^ε-benzyloxycarbonyl-5-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-5-hydroxy-L-lysine
  参考文献：
  名称：

  9-BBN作为羟基赖氨酸功能化中的便捷保护基

  摘要：

  9-BBN用于（5 R）-5-羟基-1-赖氨酸的α-氨基和α-羧基的区域选择性保护。然后将所得的9-BBN复合物用于转化中，例如N -Cbz保护，叠氮基转移，O-糖基化和O-甲硅烷基化。进一步的操作导致改进的制备羟赖氨酸和半乳糖基化羟赖氨酸结构单元的方法，适用于在标准Fmoc条件下直接用于肽合成。

  DOI：

  10.1016/j.tet.2004.04.081

文献信息

• Mild Oxidative Cleavage of 9-BBN-Protected Amino Acid Derivatives
  作者：Tobias Ankner、Thomas Norberg、Jan Kihlberg

  DOI：10.1002/ejoc.201500361

  日期：2015.6

  Protection of the amino acid moiety using 9-BBN is an effective method to enable side chain manipulations in synthesis of complex amino acids. We investigated the standard, mild method for deprotection of the 9-BBN group in methanolic chloroform, and found that it relies on a slow oxidation mediated by molecular oxygen. Building on this insight, we have developed a method that allows for a fast and

  使用 9-BBN 保护氨基酸部分是一种有效的方法，可以在复杂氨基酸的合成中进行侧链操作。我们研究了在甲醇氯仿中对 9-BBN 基团进行脱保护的标准温和方法，发现它依赖于由分子氧介导的缓慢氧化。基于这一见解，我们开发了一种方法，可以使用简单的过氧酸试剂进行快速和选择性的脱保护。在 Fmoc 保护后，一系列氨基酸衍生物（包括羟赖氨酸的半乳糖基化衍生物）的产物以 >90% 的产率分离。
• An Improved Synthesis of a Galactosylated Hydroxylysine Building Block and its use in Solid-Phase Glycopeptide Synthesis
  作者：Björn Holm、Johan Broddefalk、Sara Flodell、Eric Wellner、Jan Kihlberg

  DOI：10.1016/s0040-4020(00)00061-2

  日期：2000.3

  glycosyl donor. Best results were obtained with Fmoc-Hyl(Cbz)-OAll, which was glycosylated in 80% yield. Removal of the allyl group gave a β-d-galactosylated building block which was used in solid-phase synthesis of a glycopeptide from type II collagen. Such glycopeptides are required for studies of rheumatoid arthritis in a mouse that is transgenic for HLA-DR4, i.e. the class II MHC molecule associated with

  在（5 R）-5-羟基-1-赖氨酸的不同保护基团中，以乙酰溴半乳糖为糖基供体，在硅酸银促进的糖基化反应中进行了研究。使用Fmoc-Hyl（Cbz）-OAll可获得最佳结果，该糖基化率为80％。除去烯丙基得到β-d-半乳糖基化的结构单元，该结构单元用于从II型胶原的固相合成糖肽。对于在HLA-DR4（即与人类风湿病有关的II类MHC分子）转基因的小鼠中，类风湿关节炎的研究需要这种糖肽。
• Side-chain and backbone amide bond requirements for glycopeptide stimulation of T-cells obtained in a mouse model for rheumatoid arthritis
  作者：Lotta Holm、Robert Bockermann、Erik Wellner、Johan Bäcklund、Rikard Holmdahl、Jan Kihlberg

  DOI：10.1016/j.bmc.2006.05.023

  日期：2006.9

  Collagen induced arthritis (CIA) is the most studied animal model for rheumatoid arthritis and is associated with the MHC class II molecule A(q). T-cell recognition of a peptide from type II collagen, C11256-270, bound to A(q) is a requirement for development of CIA. Lysine 264 is the major T-cell recognition site of C11256-270 and CIA is in particular associated with recognition of lysine 264 after posttranslational hydroxylation and subsequent attachment of a beta-D-galactopyranosyl moiety. In this paper we have studied the structural requirements of collagenous glycopeptides required for T-cell stimulation, as an extension of earlier studies of the recognition of the galactose moiety. Synthesis and evaluation of alanine substituted glycopeptides revealed that there are T-cells that only recognise the galactosylated hydroxylysine 264, and no other amino acid side chains in the peptide. Other T-cells also require glutamic acid 266 as a T-cell contact point. Introduction of a methylene ether isostere instead of the amide bond between residues 260 and 261 allowed weaker recognition by some, but not all, of the T-cells. Altogether, these results allowed us to propose a model for glycopeptide recognition by the T-cells, where recognition from one or the other side of the galactose moiety could explain the different binding patterns of the T-cells. (c) 2006 Elsevier Ltd. All rights reserved.