methyl 4-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-2,3-O-isopropylidene-α-L-rhamnopyranoside | 311778-87-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 4-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-2,3-O-isopropylidene-α-L-rhamnopyranoside
• 英文别名: methyl (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-(1->4)-2,3-O-isopropylidene-α-L-rhamnopyranoside；methyl 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl-α-(1,4)-2,3-O-isopropylidene-1-α-L-rhamnopyranoside；methyl (2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-2,3-O-isopropylidene-α-L-rhamnopyranoside；methyl (2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-(1→4)-2,3-O-isopropylidene-α-L-rhamnopyranoside；(3aR,4R,6S,7S,7aR)-4-methoxy-2,2,6-trimethyl-7-(((2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran；(3aR,4R,6S,7S,7aR)-4-methoxy-2,2,6-trimethyl-7-[(2R,3R,4S,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]oxy-4,6,7,7a-tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyran
• CAS: 311778-87-7
• 化学式: C₄₄H₅₂O₁₀
• 分子量: 740.891
• InChiKey: JPIVFPPKRYOYSI-XXYXAPTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  54
• 可旋转键数：
  16
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  92.3
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 4-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-2,3-O-isopropylidene-α-L-rhamnopyranoside 在 三氟甲磺酸三甲基硅酯 、 camphor-10-sulfonic acid 、 水 、 三氟乙酸 作用下， 以 乙醚 、 二氯甲烷 、 氯仿 为溶剂， 反应 4.25h， 生成 methyl (2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl)-(1->3)-[(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-(1->4)]-2-O-benzoyl-α-L-rhamnopyranoside
  参考文献：
  名称：

  Synthesis of the Methyl Glycosides of a Di- and Two Trisaccharide Fragments Specific for theShigella flexneriSerotype 2aO-Antigen

  摘要：

  The stereocontrolled synthesis of methyl alpha-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranoside (EC, 1), methyl alpha-L-rhamnopyranosyl-(1-->3)-[alpha-D-glucopyra- osyl-(1-->4)]-alpha-L-rhamnopyranoside (B(E)C, 3) and methyl alpha-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-2-acetamido-2-deoxy-beta-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a. Emphasis was put on the construction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl fluoride (8) as the donor. Condensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyloside-alpha-L-rhamnopyranoside (11) and 8 afforded the fully protected alpha E-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding beta E-anomer 21. Deacetalation and regioselective benzoylation of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25. Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively. The corresponding beta E-disaccharide, namely, methyl beta-D-glucopyranosyl-(1-->4)-a-L-rhamnopyranoside (PEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the coupling of a precursor to residue E and a disaccharide CD. Route 2 was based on the condensation of an appropriate EC donor and a precursor to residue D. The former route afforded a 1:2 mixture of the alpha E and PE condensation products which could not be separated, neither at this stage, nor after deacetalation. In route 2, the required alpha E-anomer was isolated at the disaccharide stage and transformed into 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl-(1-->4)-2,3-di-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyran-oside (19) was preferred to its benzylidene analogue as the precursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.

  DOI：

  10.1080/07328300008544123
• 作为产物：
  描述：

  p-methylphenyl 2,3,4,6-tetra-O-benzyl-thio-β-D-glucopyranoside 在 N-甲酰吗啉 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 4-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-2,3-O-isopropylidene-α-L-rhamnopyranoside
  参考文献：
  名称：

  基于原位加合物转化的灵活的1,2-顺式α-糖基化策略

  摘要：

  已经开发了一种针对多种糖基供体和受体的灵活的1,2-顺式α-选择性糖基化策略，该策略基于原位加合物转化方案。基于此策略，可以获取NFM衍生品和碘化物共价加合物进行糖基化。使用低温NMR光谱法，检测到上述糖基加合物。

  DOI：

  10.1039/c7ob00839b

文献信息

• Dimethylformamide: An Unusual Glycosylation Modulator
  作者：Shao-Ru Lu、Yen-Hsun Lai、Jiun-Han Chen、Chih-Yueh Liu、Kwok-Kong Tony Mong

  DOI：10.1002/anie.201100076

  日期：2011.8.1

  A simple solution: When N,N‐dimethylformamide was used to direct the stereochemical course of glycosylation reactions, 1,2‐cis glycosylation products were formed with excellent selectivity. A straightforward highly α‐stereoselective glycosylation involving preactivation (see scheme) should find broad application and be especially useful for sequential glycosylation reactions to form oligosaccharides

  一个简单的解决方案：当使用N，N-二甲基甲酰胺指导糖基化反应的立体化学过程时，会形成1,2-顺式糖基化产物，选择性极好。涉及预激活的直接的高度α-立体选择性糖基化反应（请参见方案）应该得到广泛的应用，对于顺序糖基化反应形成寡糖特别有用。LG =离开小组。
• Diastereoselective sp³ C–O Bond Formation via Visible Light-Induced, Copper-Catalyzed Cross-Couplings of Glycosyl Bromides with Aliphatic Alcohols
  作者：Fei Yu、Jalen L. Dickson、Ravi S. Loka、Hengfu Xu、Richard N. Schaugaard、H. Bernhard Schlegel、Long Luo、Hien M. Nguyen

  DOI：10.1021/acscatal.0c01470

  日期：2020.6.5

  electrophiles to control α-1,2-cis selectivity. In our approach, earth-abundant copper not only acts as a photocatalyst and a bond-forming catalyst, but also enforces the stereocontrolled formation of anomeric C–O bonds. This cross-coupling protocol enables highly diastereoselective access to a wide variety of α-1,2-cis-glycosides and biologically relevant α-glycan oligosaccharides. Our work provides a foundation

  铜催化的交叉偶联反应已成为产生碳-杂原子键（许多有机分子的重要框架）的最有效方法之一。但是，由于铜的氧化加成反应迟钝，铜催化的卤代烷与烷基醇的C（sp 3）–O交叉偶联仍然难以实现。为解决这一挑战，我们开发了一种催化铜系统，该系统可借助可见光克服铜的氧化加成障碍，并有效地促进糖基溴化物与脂肪族醇的交叉偶联，从而提供具有C（sp 3）-O键的高非对映选择性。重要的是，该催化体系导致温和而有效的立体选择性构建α-1,2-顺式的方法苷，这是最重要的，但具有挑战性。通常，α-1,2-顺式糖苷C–O键形成过程中的立体化学结果是无法预测的，并且取决于与碳水化合物偶联伙伴结合的保护基的空间和电子性质。当前，最可靠的方法依赖于在碳水化合物亲电体的C2和C4位置使用手性辅助或氢键引导基团来控制α-1,2-顺式选择性。在我们的方法中，富含地球的铜不仅充当光催化剂和形成键的催化剂，而且还增强了异头C-O键的立体
• Halogen-bond-assisted radical activation of glycosyl donors enables mild and stereoconvergent 1,2-cis-glycosylation
  作者：Chen Zhang、Hao Zuo、Ga Young Lee、Yike Zou、Qiu-Di Dang、K. N. Houk、Dawen Niu

  DOI：10.1038/s41557-022-00918-z

  日期：2022.6

  2-cis-glycosylation without using metals, strong (Lewis) acids, elaborate catalysts or labile substrates. Our method operates by a unique mechanism: it activates glycosyl donors through a radical cascade rather than the conventional acid-promoted, ionic process. As elucidated by computational and experimental studies, the allyl glycosyl sulfones (as donors) form halogen bond complexes with perfluoroalkyl iodides, which—merely

  碳水化合物的化学已有 100 多年的历史，但仍然非常需要简单、立体选择性和高效的糖基化方法来促进各学科对糖的研究。在这里，我们报告了 1,2- cis-糖基化不使用金属、强（路易斯）酸、精细催化剂或不稳定底物。我们的方法通过一种独特的机制运作：它通过自由基级联激活糖基供体，而不是传统的酸促进离子过程。正如计算和实验研究所阐明的，烯丙基糖基砜（作为供体）与全氟烷基碘形成卤素键复合物，仅通过可见光照射，通过自由基中间体断裂，得到亲电子糖基碘。各种亲核试剂的原位捕获以立体收敛的方式提供具有挑战性的 1,2-顺式-糖苷。这种不含金属和酸的反应对官能团表现出显着的耐受性。高立体选择性适用于广泛的供体。该研究表明，简单的 C2-烷氧基可以作为构建 1,2-顺式-糖苷键的有效导向基团。
• Glycosyl <i>o</i>-[1-(<i>p</i>-MeO-Phenyl)vinyl]benzoates (PMPVB) as Easily Accessible, Stable, and Reactive Glycosyl Donors for O-, S-, and C-Glycosylations under Brønsted Acid Catalysis
  作者：Suvendu Halder、Rupa Bai Addanki、Sangay Moktan、Pavan K. Kancharla

  DOI：10.1021/acs.joc.2c00093

  日期：2022.6.3

  alkene-based glycosyl donors that can be activated with catalytic amounts of a Brønsted acid. This activation protocol not only allows us to synthesize O-glycosides but also can successfully provide S- and C-linked glycosides. The armed and disarmed donors lead to product formation in 5 min, showcasing the high reactivity of the donors. Competitive experiments show that the PMPVB donors are much more

  适用于 O- 和 S- 糖基化合成的方法相对较少，因为常用的促进剂（如卤源或金催化剂）与作为亲核试剂的硫醇不相容。在这里，我们将 ( p -MeO) 苯基乙烯基苯甲酸酯 (PMPVB) 作为易于获得、稳定且具有反应性的基于烯烃的糖基供体，可以用催化量的布朗斯台德酸活化。这个激活协议不仅允许我们合成O-糖苷还可以成功地提供S-和C-连接的糖苷。武装和解除武装的捐助者在 5 分钟内形成产物，展示了捐助者的高反应性。竞争性实验表明，即使在 NIS/TMSOTf 条件下，PMPVB 供体也比相应的 PVB 供体更具反应性，而 PVB 供体的反应性不足以在布朗斯台德酸条件下被有效激活。通过合成三糖也展示了催化糖基化方案的潜力。PMPVB 供体的布朗斯台德酸活化还允许以立体选择性方式获得C-糖苷。只需两个步骤即可轻松获取多克规模的供体糖苷配基，这使得 PMPVB 供体成为极具吸引力的替代品。
• α-Selective Glucosylation Can Be Achieved with 6-<i>O</i>-<i>para</i>-Nitrobenzoyl Protection
  作者：Helle H. Trinderup、Line Juul-Madsen、Laura Press、Michael Madsen、Henrik H. Jensen

  DOI：10.1021/acs.joc.2c01475

  日期：2022.11.4

  A systematic study of the effect of various 6-O-acyl groups on anomeric selectivity in glucosylations with thioglycoside donors was conducted. All eight different esters were found to induce moderate-to-high α-selectivity in glucosylation with l-menthol with the best being 6-O-p-nitrobenzoyl. The effect appears to be general across various glucosyl acceptors, glucosyl donor types, and modes of activation

  系统研究了各种 6- O-酰基对硫代糖苷供体的糖基化端基异构选择性的影响。发现所有八种不同的酯在与l-薄荷醇的糖基化中诱导中等到高的 α-选择性，其中最好的是 6- O - p-硝基苯甲酰。这种效应似乎对各种糖基受体、糖基供体类型和激活模式具有普遍性。没有发现支持远端参与的证据。