β-1,5-anhydro-1-C-phenyl-2,3,4,6-tetra-O-benzyl-D-glucitol | 112219-64-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: β-1,5-anhydro-1-C-phenyl-2,3,4,6-tetra-O-benzyl-D-glucitol
• 英文别名: β-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-C-phenyl-D-glucitol；(2,3,4,6-tetra-O-benzyl-D-glucopyranosyl)-benzene β anomer；2,3,4,6-tetra-O-benzyl-β-D-1C-phenyl-1-deoxyglucose；2,3,4,6-tetra-O-benzyl-1-C-phenyl-β-D-glucopyranoside；(2R,3R,4R,5S,6S)-3,4,5-tris(benzyloxy)-2-((benzyloxy)methyl)-6-phenyltetrahydro-2H-pyran；2,3,4,6-tetra-O-benzyl-1-deoxy-1-phenyl-β-D-glucopyranose；1-C-phenyl-β-D-glucopyranoside；(2S,3S,4R,5R,6R)-2-phenyl-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxane
• CAS: 112219-64-4
• 化学式: C₄₀H₄₀O₅
• 分子量: 600.755
• InChiKey: DICBLRVEAXYKQL-CSISHVCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  β-1,5-anhydro-1-C-phenyl-2,3,4,6-tetra-O-benzyl-D-glucitol 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以90%的产率得到1-C-phenyl-β-D-glucopyranoside
  参考文献：
  名称：

  C-Glycosides. 7. Stereospecific C-glycosylation of aromatic and heterocyclic rings

  摘要：

  DOI：

  10.1021/jo00264a020
• 作为产物：
  描述：

  1,6-脱水-β-D-葡萄糖 在 咪唑 、 正丁基锂 、 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 β-1,5-anhydro-1-C-phenyl-2,3,4,6-tetra-O-benzyl-D-glucitol
  参考文献：
  名称：

  β-Selective C-Arylation of Silyl Protected 1,6-Anhydroglucose with Arylalanes: The Synthesis of SGLT2 Inhibitors

  摘要：

  The stereoselective arylation of hydroxy protected 1,6-anhydro-beta-d-glucose with arylalanes to provide beta-C-arylglucosides is reported. Modification of triarylalanes, Ar3Al, with strong Bronsted acids (HX) or AlCl3 produced more reactive arylating agents, Ar2AlX, while the incorporation of alkyl dummy ligands into the arylating agents was also viable. Me3Al and i-Bu2AlH were found useful in the in situ blocking of the C3-hydroxyl group of 2,4-di-O-TBDPS protected 1,6-anhydroglucose. The utility of the method was demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin.

  DOI：

  10.1021/jo502839e

文献信息

• Organometallics in organic synthesis. Applications of a new diorganozinc reaction to the synthesis of C-glycosyl compounds with evidence for an oxonium-ion mechanism
  作者：Alan P. Kozikowski、Toshiro Konoke、Allen Ritter

  DOI：10.1016/s0008-6215(00)90882-6

  日期：1987.12

  features of a new organozinc-based substitution process [heteroatom-C-(R1,R2)-SPh + R3(2)Zn----heteroatom-C-(R1,R2,R3)], first discovered during a total synthesis of the alkaloid mycotoxin alpha-cyclopiazonic acid, are described. Phenyl thioglycosides were valuable substrates in studying the nature of this reaction process. Since these sulfur compounds are converted into C-glycosyl compounds with some

  首次发现新的基于有机锌的取代过程[杂原子-C-（R1，R2）-SPh + R3（2）Zn ----杂原子-C-（R1，R2，R3）]的机理和立体化学特征在生物碱真菌毒素的全合成过程中，描述了α-环吡嗪酸。苯基硫代糖苷是研究该反应过程性质的有价值的底物。由于这些硫化合物以一定的立体选择性转化为C-糖基化合物，因此有机锌化学确实为这些生物活性物质提供了新的进入途径。
• Highly Stereospecific Cross-Coupling Reactions of Anomeric Stannanes for the Synthesis of C-Aryl Glycosides
  作者：Feng Zhu、Michael J. Rourke、Tianyi Yang、Jacob Rodriguez、Maciej A. Walczak

  DOI：10.1021/jacs.6b07891

  日期：2016.9.21

  We demonstrate that configurationally stable anomeric stannanes undergo a stereospecific cross-coupling reaction with aromatic halides in the presence of a palladium catalyst with exceptionally high levels of stereocontrol. In addition to a broad substrate scope (>40 examples), this reaction eliminates critical problems inherent to nucleophilic displacement methods and is applicable to (hetero)aromatics

  我们证明，在具有极高立体控制水平的钯催化剂存在下，构型稳定的异头锡烷与芳族卤化物发生立体定向交叉偶联反应。除了广泛的底物范围（> 40 个例子）之外，该反应消除了亲核置换方法固有的关键问题，适用于（杂）芳烃、肽、药物、常见单糖和含有游离羟基的糖类。
• β-Selective <i>C</i>-Arylation of Diisobutylaluminum Hydride Modified 1,6-Anhydroglucose: Synthesis of Canagliflozin without Recourse to Conventional Protecting Groups
  作者：Julian P. Henschke、Chen-Wei Lin、Ping-Yu Wu、Wen-Shing Tsao、Jyh-Hsiung Liao、Pei-Chen Chiang

  DOI：10.1021/acs.joc.5b00601

  日期：2015.5.15

  'The beta-selective phenylation of benzyl and boronate protected 1,6-anhydroglucose and the direct phenylation of unprotected 1,6-anhydroglucose (10), pretreated with i-Bu2AlH, i-Bu3Al, Et3Al, Me3Al, or n-octyl(3)Al, with triphenylalane or aryl(chloro)alanes is reported. The utility of the unprotected version of the method is demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin (1a), from commercially available 10 in one C-C bond-forming step. This approach circumvents the need for conventional protecting groups, and therefore no formal protection and deprotection steps are required.

  报道了对苯甲基和硼酸酯保护的1,6-脱水葡萄糖的β选择性苯基化，以及对未保护的1,6-脱水葡萄糖（10），在用i-Bu2AlH、i-Bu3Al、Et3Al、Me3Al或n-octyl(3)Al预处理后，使用三苯基烷基或芳基(氯)烷基化试剂的直接苯基化。该方法的未保护版本的实用性通过从商业可得的10在一步C-C键形成步骤中合成SGLT2抑制剂卡格列净（1a）得到证明。该方法避免了传统保护基团的需要，因此不需要正式的保护和去保护步骤。
• Diastereoselective Ni-Catalyzed Negishi Cross-Coupling Approach to Saturated, Fully Oxygenated <i>C</i>-Alkyl and <i>C</i>-Aryl Glycosides
  作者：Hegui Gong、Michel R. Gagné

  DOI：10.1021/ja8041564

  日期：2008.9.10

  A Ni-catalyzed Negishi cross-coupling approach to C-glycosides is described with an emphasis on C-aryl glycosides. The combination of NiCl2/PyBox in N,N'-dimethylimidazolidinone (DMI) enabled the synthesis of C-alkyl glycosides under mild reaction conditions. Moderate yields and beta-selectivities were obtained for C-glucosides, and good yields and high alpha-selectivities were the norm for C-mannosides

  介绍了一种 Ni 催化的 Negishi 交叉偶联方法来处理 C-糖苷，重点是 C-芳基糖苷。NiCl2/PyBox 在 N,N'-二甲基咪唑烷酮 (DMI) 中的组合能够在温和的反应条件下合成 C-烷基糖苷。C-葡萄糖苷获得了中等的产量和β-选择性，而良好的产量和高α-选择性是C-甘露糖苷的标准。对于 C-芳基糖苷，在 N,N-二甲基甲酰胺 (DMF) 中使用 Ni(COD)2/(t)Bu-Terpy 的反应通常具有高产率，并提供具有高 β-选择性（1:>10 α: beta) 和 C-甘露糖苷具有中等 alpha 选择性 (3:1 alpha:beta)；α-C-芳基糖苷可以通过 Ni(COD)2/PyBox 在 DMF (>20:1 alpha:beta) 中的组合获得。集体研究表明，C-糖苷的立体化学控制取决于底物和催化剂的组合。Negishi 协议显示出出色的官能团耐受性，正如其在天然产物沙甲素
• An Efficient Synthesis of β-<i>C</i>-Glycosides Based on the Conformational Restriction Strategy:  Lewis Acid Promoted Silane Reduction of the Anomeric Position with Complete Stereoselectivity
  作者：Masaru Terauchi、Hiroshi Abe、Akira Matsuda、Satoshi Shuto

  DOI：10.1021/ol048525+

  日期：2004.10.1

  [reaction: see text] The reduction of glyconolactols having an anomeric carbon substituent by Et(3)SiH/TMSOTf proceeded with complete stereoselectivity to produce the corresponding beta-C-glycosides when the substrates were conformationally restricted in the (4)C(1)-chair form by a 3,4-O-cyclic diketal or a 4,6-O-benzylidene protecting group. Thus, the efficient construction of beta-C-glycosides was

  [反应：参见正文]当底物在（4）C（1）中构象受限时，通过Et（3）SiH / TMSOTf还原具有异头碳取代基的糖基内酯完全立体选择性生成相应的β-C-糖苷。 ）-椅子形式由3,4-O-环双缩酮或4,6-O-亚苄基保护基组成。因此，在构象限制策略的基础上实现了β-C-糖苷的有效构建。