5-乙酰氨基-7,8,9-三-O-乙酰基-5-N,4-O-羰基-3,5-二脱氧-2-S-苯基-2-硫代-Β-D-甘油-D-半乳-2-吡喃神经氨酸甲酯 | 934591-76-1

• 物质功能分类: 医药中间体 - 吡喃类化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 5-乙酰氨基-7,8,9-三-O-乙酰基-5-N,4-O-羰基-3,5-二脱氧-2-S-苯基-2-硫代-Β-D-甘油-D-半乳-2-吡喃神经氨酸甲酯
• 中文别名: 5-乙酰氨基-7,8,9-三-O-乙酰基-5-N,4-O-羰基-3,5-二脱氧-2-S-苯基-2-硫代-β-D-甘油-D-半乳-2-吡喃神经氨酸甲酯
• 英文名称: methyl (phenyl 5-acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl-3,5-dideoxy-2-thio-D-glycero-β-D-galacto-non-2-ulopyranoside)onate
• 英文别名: Methyl 5-Acetamido-7,8,9-tri-O-acetyl-5-N,4-O-carbonyl-3,5-dideoxy-2-S-phenyl-2-thio-D-glycero-beta-D-galacto-2-nonulopyranosylonate；methyl (3aR,4R,6R,7aS)-3-acetyl-2-oxo-6-phenylsulfanyl-4-[(1S,2R)-1,2,3-triacetyloxypropyl]-3a,4,7,7a-tetrahydropyrano[3,4-d][1,3]oxazole-6-carboxylate
• CAS: 934591-76-1
• 化学式: C₂₅H₂₉NO₁₂S
• 分子量: 567.571
• InChiKey: CVMYPHWPKCZUMN-TUTCKEIYSA-N

物化性质

• 熔点：
  150.0 to 154.0 °C
• 沸点：
  658.0±55.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  186
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  5-乙酰氨基-7,8,9-三-O-乙酰基-5-N,4-O-羰基-3,5-二脱氧-2-S-苯基-2-硫代-Β-D-甘油-D-半乳-2-吡喃神经氨酸甲酯 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以100%的产率得到methyl (phenyl 5-acetamido-3,5-dideoxy-2-thio-D-glycero-β-D-galactonon-2-ulopyranoside)onate
  参考文献：
  名称：

  在二氯甲烷中用 N-乙酰基-5-N,4-O-羰基保护的硫唾液酸苷供体进行 O-唾液酸化：轻松选择性地裂解恶唑烷酮环

  摘要：

  制备了N-乙酰基-5- N , 4 - O-羰基保护的硫唾液酸苷供体，其结构已通过 X 射线晶体学确定，并在与各种受体的偶联中进行了测试。该供体在N-碘代琥珀酰亚胺和三氟甲磺酸原位活化方法（-40 °C 在二氯甲烷中）下与各种伯烷基和碳水化合物受体连接时具有优异的产率和 α-选择性。通过与N , N-二乙酰唾液酸供体的比较研究说明了恶唑烷酮子结构对 α-唾液酸化的有利影响，该供体表现出较差的产率和 α-选择性。唾液酸化选择性与供体的异头构型无关，但与NIS/TfOH活化方法下的反应温度高度相关。与 NIS/TfOH 方法相反，Ph 2 SO/Tf 2 O 促进在二氯甲烷中产生β-选择性偶联。N-乙酰基-5- N ,4- O-羰基保护的唾液酸苷（α-和β-端基异构体）的恶唑烷酮可以通过在温和条件下用甲醇钠处理而干净地裂解，而无需去除乙酰胺。

  DOI：

  10.1021/jo062431r
• 作为产物：
  描述：

  methyl (phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycerol-β-D-galactonon-2-ulopyranoside)onate 在 甲烷磺酸 、 三光气 、 碳酸氢钠 、 吡啶 、 4-二甲氨基吡啶 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 41.0h， 生成 5-乙酰氨基-7,8,9-三-O-乙酰基-5-N,4-O-羰基-3,5-二脱氧-2-S-苯基-2-硫代-Β-D-甘油-D-半乳-2-吡喃神经氨酸甲酯
  参考文献：
  名称：

  GM3抗原的氨基氧基衍生物的合成及其在肟连接中的应用。

  摘要：

  氨氧基GM3三糖癌抗原的异头（Neu5Acα2,3Galβ1,4Glcβ-ONH 2）已经使用线性糖基化的方法化学合成。关键步骤涉及对半乳糖受体的高度α（2,3）-立体选择性唾液酸化。Neu5Acα2,3Gal中间体被功能化为[2 +1]糖基化的供体，其中包括在还原端具有O-琥珀酰亚胺基的氨基葡萄糖作为氨基氧基前体。然后将完全脱保护的异头氨基氧基GM3三糖通过肟连接缀合到免疫相关的两性离子多糖PSA1上。

  DOI：

  10.1021/acs.joc.0c00320

文献信息

• Chemical approach for the syntheses of GM4 isomers with sialic acid to non-natural linkage positions on galactose
  作者：Kenta Kurimoto、Hatsuo Yamamura、Atsushi Miyagawa

  DOI：10.1016/j.carres.2014.10.018

  日期：2015.1

  Cell-surface glycans containing sialic acid are involved in various biological phenomena. However, the syntheses of GM4 derivatives with (2 --> 2) and (2 --> 4) linkages have not been investigated to date. In this study, sialylation of all of the hydroxyl groups on galactose were investigated for the syntheses of GM4 isomers. Regioselective sialylation was achieved via protection of galactosyl acceptors

  含有唾液酸的细胞表面聚糖参与多种生物学现象。但是，迄今尚未研究具有（2-> 2）和（2-> 4）键的GM4衍生物的合成。在这项研究中，对半乳糖上所有羟基的唾液酸化进行了研究，以合成GM4异构体。通过使用富含电子的苄基基团保护半乳糖基受体来实现区域选择性的唾液酸化。这些合成的唾液酸化聚糖将被证明是研究未知碳水化合物介导的生物学角色的有用工具。
• Screening of Neu5Acα(2–6)gal isomer preferences of siglecs with a sialic acid microarray
  作者：Rohan Yadav、Shani Leviatan Ben-Arye、Balamurugan Subramani、Vered Padler-Karavani、Raghavendra Kikkeri

  DOI：10.1039/c6ob01688j

  日期：——

  The synthesis of Neu5Acα(2–6)Gal structural analogs showed distinct binding patterns with conserved siglecs (hCD22 and mCD22) compared to rapid evolving siglecs (Siglecs -3 & -10).

  Neu5Acα(2–6)Gal结构类似物的合成显示出与保守的siglecs（hCD22和mCD22）相比，与快速进化的siglecs（Siglecs -3和-10）具有不同的结合模式。
• Synthesis and biological evaluation of sialyl-oligonucleotide conjugates targeting leukocyte B trans-membranal receptor CD22 as delivery agents for nucleic acid drugs
  作者：Gabrielle St-Pierre、Sudip Pal、Michael E. Østergaard、Tianyuan Zhou、Jinghua Yu、Michael Tanowitz、Punit P. Seth、Stephen Hanessian

  DOI：10.1016/j.bmc.2016.03.047

  日期：2016.6

  Antisense oligonucleotides (ASOs) modified with ligands which target cell surface receptors have the potential to significantly improve potency in the target tissue. This has recently been demonstrated using triantennary N-acetyl D-galactosamine conjugated ASOs. CD22 is a cell surface receptor expressed exclusively on B cells thus presenting an attractive target for B cell specific delivery of drugs. Herein, we reported the synthesis of monovalent and trivalent ASO conjugates with biphenylcarbonyl (BPC) modified sialic acids and their study as ASO delivery agents into B cells. CD22 positive cells exhibited reduced potency when treated with ligand modified ASOs and mechanistic examination suggested reduced uptake into cells potentially as a result of sequestration of ASO by other cell-surface proteins. (C) 2016 Elsevier Ltd. All rights reserved.
• A stable, commercially available sulfenyl chloride for the activation of thioglycosides in conjunction with silver trifluoromethanesulfonate
  作者：David Crich、Feng Cai、Fan Yang

  DOI：10.1016/j.carres.2008.03.002

  日期：2008.7

  p-Nitrobenzenesulfenyl chloride is a stable commercially available sulfenyl chloride that, in conjunction with silver triflate, cleanly activates a wide range of thioglycosides for glycosylation at -78 degrees C in CH2Cl2. (c) 2008 Elsevier Ltd. All rights reserved.
• Sialyl-Tn Polysaccharide A1 as an Entirely Carbohydrate Immunogen: Synthesis and Immunological Evaluation
  作者：Mengchao Shi、Kristopher A. Kleski、Kevin R. Trabbic、Jean-Paul Bourgault、Peter R. Andreana

  DOI：10.1021/jacs.6b05675

  日期：2016.11.2

  Sialyl Thomsen-nouveau (STn) is a tumor-associated carbohydrate antigen (TACA) that is overexpressed hi a variety of carcinomas such as breast, ovarian, and colon cancer. In normal tissue, STn is not detectable, which is critical for opportunities in developing cancer immunotherapies. A novel, entirely carbohydrate, semisynthetic STn-polysaccharide (PS) A1 conjugate was prepared and evaluated in CS7BL/6 mice. STn-PS A1 was combined with commercially available monophosphoryl lipid A-based adjuvant, and after immunization, ELISA indicated a strong immune response for inducing anti STn IgM/IgG antibodies. The specificity of these antibodies was concomitantly investigated using FACS analysis, and the results indicated excellent cell surface binding events to STn-expressing cancer cell lines MCF-7 and OVCAR-5. An INF-gamma ELISpot assay was conducted to further confirm a robust cellular immunity invoked by STn-PS A1. Most importantly, the raised antibodies conferred complement-dependent cellular cytotoxicity against MCF-7 and OVCAR-5 cells.