methyl 6-O-(α-D-glycopyranosyl)-(6R)-C-methyl-α-D-glucopyranoside | 133213-37-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 6-O-(α-D-glycopyranosyl)-(6R)-C-methyl-α-D-glucopyranoside
• 英文别名: methyl 6R-C-methyl-α-isomaltoside；Glc(a1-6)7-deoxy-D-gro-a-D-glcHept1Me；(2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[(1R)-1-[(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-methoxyoxan-2-yl]ethoxy]oxane-3,4,5-triol
• CAS: 133213-37-3
• 化学式: C₁₄H₂₆O₁₁
• 分子量: 370.354
• InChiKey: WSBATXJMHXXRJV-RHWKWSMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  179
• 氢给体数：
  7
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl 6-O-(α-D-glycopyranosyl)-(6R)-C-methyl-α-D-glucopyranoside 在 glucoamylase sodium acetate 作用下， 生成 D-葡萄糖
  参考文献：
  名称：

  C-6取代的异麦芽糖苷Km值降低的葡糖淀粉酶突变体

  摘要：

  摘要葡糖淀粉酶可以催化甲基6 R-C-烷基α-异麦芽糖苷的水解。在+2结合亚位点改变的Trp120→Phe突变体的甲基6 R-C-甲基-α-异麦芽糖苷的K m为0.089 mM，而野生型酶的K m为0.71 mM。这反映出该基板的低K m值是原来的八倍。然而，与野生型葡糖淀粉酶相比，突变体的k cat降低了200倍。随着取代基大小增加到6 R-C-乙基和-异丙基，Trp120→Phe和野生型葡糖淀粉酶的K m值相似，而突变体的k cat分别增加10倍和100倍，接近野生型。类型值。通过消除Trp120→Phe葡糖淀粉酶中Trp120 NE1与Glu179 OE2的氢键，消除了一般酸催化剂Glu179周围结构的完整性，似乎被较大的C-6取代基所抵消。酶和底物类似物之间的明显互补性强调了疏水力对蛋白质与碳水化合物相互作用的有利影响。野生型葡糖淀粉酶和Val181→Ala / Asn182→Ala

  DOI：

  10.1016/s0008-6215(98)00283-3
• 作为产物：
  描述：

  methyl 6-O-(6-O-acetyl-2,3,4-tri-O-benzyl-α-D-glucopyranosyl)-2,3,4-tri-O-benzyl-(6R)-C-methyl-α-D-glucopyranoside 在 palladium on activated charcoal 氢气 、 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 methyl 6-O-(α-D-glycopyranosyl)-(6R)-C-methyl-α-D-glucopyranoside
  参考文献：
  名称：

  The syntheses of 6-C-alkyl derivatives of methyl α-isomaltoside for a study of the mechanism of hydrolysis by amyloglucosidase

  摘要：

  为了研究引入不同大小烷基基团对酶类淀粉酶（EC 3.2.1.3，通常称为葡萄糖淀粉酶）对α-糖苷键水解速率的影响，合成了甲基α-异麦芽糖苷（1）的异构体（6aR）-和（6aS）-C-烷基（甲基、乙基和异丙基）衍生物。之前已确定，甲基（6aR）-C-甲基α-异麦芽糖苷的水解速率约比甲基α-异麦芽糖苷快大约2倍，比其S-异构体快大约8倍。最近还发表了乙基和异丙基类似物的水解动力学。正如从分子模型计算所预期的那样，所有的R-异构体都是良好的底物。提出了基于传统机械理论的催化理论，包括通过氢键将4a-羟基与色氨酸和精氨酸单元连接起来，以促进激活复合物向产物的分解。建议初始形成的复合物向过渡态的激活是通过由受扰动的水分子在多胶性底物和结合位点表面的脱水和分子间氢键的建立释放的能量来辅助的，即微热力学。周围环绕结合位点的芳香氨基酸壳层阻碍了热量向大量溶液的传播。这种屏蔽层已知位于凝集素和特异性碳水化合物抗体的结合位点周围，并被认为是必要的，以防止破坏分子间氢键，这对于复合物的稳定性至关重要。这些特征与结合位点内反应分子的精致立体电子排布一起，为在常温和接近中性pH下的催化提供了合理解释。合成涉及将烷基格氏试剂加到甲基6-醛基-α-D-葡萄糖吡喃糖。加成有利于S-异构体的形成，超过90%。通过使用传统方法在手性中心进行异构化，得到了活性R-异构体的有用量。在溴离子催化条件下对所得醇进行糖基化，提供了甲基（6aS）-和（6aR）-C-烷基-七O-苄基-α-异麦芽糖苷。对苄基团的催化氢解得到了期望的二糖。通过1H核磁共振研究，确定了绝对构型并提供了构象偏好的证据。关键词：淀粉酶（AMG），外部异构效应，6-C-烷基-α-D-葡萄糖吡喃糖和异麦芽糖苷，酶催化机制。

  DOI：

  10.1139/v01-005

文献信息

• The syntheses of 6-<i>C</i>-alkyl derivatives of methyl α-isomaltoside for a study of the mechanism of hydrolysis by amyloglucosidase
  作者：Ulrike Spohr、Nghia Le、Chang-Chun Ling、Raymond U Lemieux

  DOI：10.1139/v01-005

  日期：2001.2.1

  The epimeric (6aR)- and (6aS)-C-alkyl (methyl, ethyl and isopropyl) derivatives of methyl α-isomaltoside (1) were synthesized in order to examine the effects of introducing alkyl groups of increasing bulk on the rate of catalysis for the hydrolysis of the interunit α-glycosidic bond by the enzyme amyloglucosidase, EC 3.2.1.3, commonly termed glucoamylase (AMG). It was previously established that methyl (6aR)-C-methyl α-isomaltoside is hydrolysed about 2 times faster than methyl α-isomaltoside and about 8 times faster than its S-isomer. The kinetics for the hydrolyses of the ethyl and isopropyl analogs were also recently published. As was expected from molecular model calculations, all the R-epimers are good substrates. A rationale is presented for the catalysis based on conventional mechanistic theories that includes the assistance for the decomposition of the activated complex to products by the presence of a hydrogen bond, which connects the 4a-hydroxyl group to the tryptophane and arginine units. It is proposed that activation of the initially formed complex to the transition state is assisted by the energy released as a result of both of the displacement of perturbed water molecules of hydration at the surfaces of both the polyamphiphilic substrate and the combining site and the establishment of intermolecular hydrogen bonds, i.e., micro-thermodynamics. The dissipation of the heat to the bulk solution is impeded by a shell of aromatic amino acids that surround the combining site. Such shields are known to be located around the combining sites of lectins and carbohydrate specific antibodies and are considered necessary to prevent the disruption of the intermolecular hydrogen bonds, which are of key importance for the stability of the complex. These features together with the exquisite stereoelectronic dispositions of the reacting molecules within the combining site offer a rationalization for the catalysis at ambient temperatures and near neutral pH. The syntheses involved the addition of alkyl Grignard reagents to methyl 6-aldehydo-α-D-glucopyranoside. The addition favoured formation of the S-epimers by over 90%. Useful amounts of the active R-isomers were obtained by epimerization of the chiral centers using conventional methods. Glycosylation of the resulting alcohols under conditions for bromide-ion catalysis, provided methyl (6aS)- and (6aR)-C-alkyl-hepta-O-benzyl-α-isomaltosides. Catalytic hydrogenolysis of the benzyl groups afforded the desired disaccharides. ¹H NMR studies established the absolute configurations and provided evidence for conformational preferences.Key words: amyloglucosidase (AMG), exo-anomeric effect, 6-C-alkyl-α-D-glucopyranosides and isomaltosides, mechanism of enzyme catalysis.

  为了研究引入不同大小烷基基团对酶类淀粉酶（EC 3.2.1.3，通常称为葡萄糖淀粉酶）对α-糖苷键水解速率的影响，合成了甲基α-异麦芽糖苷（1）的异构体（6aR）-和（6aS）-C-烷基（甲基、乙基和异丙基）衍生物。之前已确定，甲基（6aR）-C-甲基α-异麦芽糖苷的水解速率约比甲基α-异麦芽糖苷快大约2倍，比其S-异构体快大约8倍。最近还发表了乙基和异丙基类似物的水解动力学。正如从分子模型计算所预期的那样，所有的R-异构体都是良好的底物。提出了基于传统机械理论的催化理论，包括通过氢键将4a-羟基与色氨酸和精氨酸单元连接起来，以促进激活复合物向产物的分解。建议初始形成的复合物向过渡态的激活是通过由受扰动的水分子在多胶性底物和结合位点表面的脱水和分子间氢键的建立释放的能量来辅助的，即微热力学。周围环绕结合位点的芳香氨基酸壳层阻碍了热量向大量溶液的传播。这种屏蔽层已知位于凝集素和特异性碳水化合物抗体的结合位点周围，并被认为是必要的，以防止破坏分子间氢键，这对于复合物的稳定性至关重要。这些特征与结合位点内反应分子的精致立体电子排布一起，为在常温和接近中性pH下的催化提供了合理解释。合成涉及将烷基格氏试剂加到甲基6-醛基-α-D-葡萄糖吡喃糖。加成有利于S-异构体的形成，超过90%。通过使用传统方法在手性中心进行异构化，得到了活性R-异构体的有用量。在溴离子催化条件下对所得醇进行糖基化，提供了甲基（6aS）-和（6aR）-C-烷基-七O-苄基-α-异麦芽糖苷。对苄基团的催化氢解得到了期望的二糖。通过1H核磁共振研究，确定了绝对构型并提供了构象偏好的证据。关键词：淀粉酶（AMG），外部异构效应，6-C-烷基-α-D-葡萄糖吡喃糖和异麦芽糖苷，酶催化机制。
• Glucoamylase mutants with decreased Km-values for C-6 substituted isomaltosides
  作者：Torben P. Frandsen、Monica M. Palcic、Claude Dupont、Birte Svensson

  DOI：10.1016/s0008-6215(98)00283-3

  日期：1998.12

  Abstract Glucoamylase can catalyze the hydrolysis of methyl 6 R - C -alkyl α-isomaltosides. A Trp120→Phe mutant altered in the +2 binding subsite had a K m of 0.089 mM for methyl 6 R - C -methyl-α-isomaltoside compared to a K m of 0.71 mM for the wild-type enzyme. This reflects an eight-fold lower K m for this substrate; however, the k cat for the mutant was decreased 200-fold compared with the wild-type

  摘要葡糖淀粉酶可以催化甲基6 R-C-烷基α-异麦芽糖苷的水解。在+2结合亚位点改变的Trp120→Phe突变体的甲基6 R-C-甲基-α-异麦芽糖苷的K m为0.089 mM，而野生型酶的K m为0.71 mM。这反映出该基板的低K m值是原来的八倍。然而，与野生型葡糖淀粉酶相比，突变体的k cat降低了200倍。随着取代基大小增加到6 R-C-乙基和-异丙基，Trp120→Phe和野生型葡糖淀粉酶的K m值相似，而突变体的k cat分别增加10倍和100倍，接近野生型。类型值。通过消除Trp120→Phe葡糖淀粉酶中Trp120 NE1与Glu179 OE2的氢键，消除了一般酸催化剂Glu179周围结构的完整性，似乎被较大的C-6取代基所抵消。酶和底物类似物之间的明显互补性强调了疏水力对蛋白质与碳水化合物相互作用的有利影响。野生型葡糖淀粉酶和Val181→Ala / Asn182→Ala