phenyl (2,6-di-O-acetyl-β-D-galactopyranosyl)-(1->4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside | 1363661-24-8

• 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: phenyl (2,6-di-O-acetyl-β-D-galactopyranosyl)-(1->4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside
• 英文别名: phenyl (2,6-di-O-acetyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside
• CAS: 1363661-24-8
• 化学式: C₂₈H₃₆O₁₅S
• 分子量: 644.651
• InChiKey: WBFMKORVBCCARN-NDJSZMGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.26
• 重原子数：
  44.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  199.65
• 氢给体数：
  2.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  phenyl (2,6-di-O-acetyl-β-D-galactopyranosyl)-(1->4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside 在 吡啶 、 三氟甲磺酸酐 、 对甲苯磺酸 、 sodium nitrite 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.0h， 生成 phenyl (2,6-di-O-acetyl-4-O-(18)O-acetyl-β-D-glucopyranosyl)-(1->4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  Transition State Analysis of Vibrio cholerae Sialidase-Catalyzed Hydrolyses of Natural Substrate Analogues

  摘要：

  A series of isotopically labeled natural substrate analogues (phenyl 5-N-acetyl-alpha-u-neuraminyl-(2 -> 3)-alpha-D-galactopyranosyl-(2 -> 4)-1-thio-beta-D-glucopyranoside; Neu5Ac alpha 2,3Lac beta SPh, and the corresponding 2 -> 6 isomer) were prepared chemoenzymatically in order to characterize, by use of multiple kinetic isotope effect (KIE) measurements, the glycosylation transition states for Vibrio cholerae sialidase-catalyzed hydrolysis reactions. The derived KIEs for Neu5Ac alpha 2,3Lac beta SPh for the ring oxygen (V-18/K), leaving group oxygen (V-18/K), C3-S deuterium (V-D/K-S) and C3-R deuterium (V-D/K-R) are 1.029 +/- 0.002, 0.983 +/- 0.001, 1.034 +/- 0.002, and 1.043 +/- 0.002, respectively. In addition, the KIEs for Neu5Ac alpha 2,6 beta SPh for C3-S deuterium (V-D/K-S) and C3-R deuterium (V-D/K-R) are 1.021 +/- 0.001 and 1.049 +/- 0.001, respectively. The glycosylation transition state structures for both Neu5Ac alpha 2,3Lac beta SPh and Neu5Ac alpha 2,6Lac beta SPh were modeled computationally using the experimental KIE values as goodness of fit criteria. Both transition states are late with largely cleaved glycosidic bonds coupled to pyranosyl ring flattening (H-4(5) half-chair conformation) with little or no nucleophilic involvement of the enzymatic tyrosine residue. Notably, the transition state for the catalyzed hydrolysis of Neu5Ac alpha 2,6 beta SPh appears to incorporate a lesser degree of general-acid catalysis, relative to the 2,3-isomer.

  DOI：

  10.1021/ja208564y
• 作为产物：
  描述：

  Phenyl 2,3,6-tri-O-acetyl-4-O-(2,6-di-O-acetyl-3,4-O-isopropylidene-β-D-galactopyranosyl)-1-thio-β-D-glucopyranoside 在 溶剂黄146 作用下， 以 水 为溶剂， 以85%的产率得到phenyl (2,6-di-O-acetyl-β-D-galactopyranosyl)-(1->4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  Transition State Analysis of Vibrio cholerae Sialidase-Catalyzed Hydrolyses of Natural Substrate Analogues

  摘要：

  A series of isotopically labeled natural substrate analogues (phenyl 5-N-acetyl-alpha-u-neuraminyl-(2 -> 3)-alpha-D-galactopyranosyl-(2 -> 4)-1-thio-beta-D-glucopyranoside; Neu5Ac alpha 2,3Lac beta SPh, and the corresponding 2 -> 6 isomer) were prepared chemoenzymatically in order to characterize, by use of multiple kinetic isotope effect (KIE) measurements, the glycosylation transition states for Vibrio cholerae sialidase-catalyzed hydrolysis reactions. The derived KIEs for Neu5Ac alpha 2,3Lac beta SPh for the ring oxygen (V-18/K), leaving group oxygen (V-18/K), C3-S deuterium (V-D/K-S) and C3-R deuterium (V-D/K-R) are 1.029 +/- 0.002, 0.983 +/- 0.001, 1.034 +/- 0.002, and 1.043 +/- 0.002, respectively. In addition, the KIEs for Neu5Ac alpha 2,6 beta SPh for C3-S deuterium (V-D/K-S) and C3-R deuterium (V-D/K-R) are 1.021 +/- 0.001 and 1.049 +/- 0.001, respectively. The glycosylation transition state structures for both Neu5Ac alpha 2,3Lac beta SPh and Neu5Ac alpha 2,6Lac beta SPh were modeled computationally using the experimental KIE values as goodness of fit criteria. Both transition states are late with largely cleaved glycosidic bonds coupled to pyranosyl ring flattening (H-4(5) half-chair conformation) with little or no nucleophilic involvement of the enzymatic tyrosine residue. Notably, the transition state for the catalyzed hydrolysis of Neu5Ac alpha 2,6 beta SPh appears to incorporate a lesser degree of general-acid catalysis, relative to the 2,3-isomer.

  DOI：

  10.1021/ja208564y

文献信息

• Synthesis of an Aminooxy Derivative of the GM3 Antigen and Its Application in Oxime Ligation
  作者：Kristopher A. Kleski、Mengchao Shi、Matthew Lohman、Gabrielle T. Hymel、Vinod K. Gattoji、Peter R. Andreana

  DOI：10.1021/acs.joc.0c00320

  日期：2020.12.18

  The anomeric aminooxy GM3 trisaccharide cancer antigen (Neu5Acα2,3Galβ1,4Glcβ-ONH2) has been chemically synthesized using a linear glycosylation approach. The key step involves a highly α(2,3)-stereoselective sialylation to a galactose acceptor. The Neu5Acα2,3Gal intermediate was functionalized as a donor for a [2 + 1] glycosylation, including a glucose acceptor that featured an O-succinimidyl group

  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。