1,6-anhydro-2,3,4-tri-O-tert-butyldimethylsilyl-β-D-glucopyranose

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 英文名称: 1,6-anhydro-2,3,4-tri-O-tert-butyldimethylsilyl-β-D-glucopyranose
• 英文别名: [(1R,2R,3S,4R,5R)-2,3-bis[[tert-butyl(dimethyl)silyl]oxy]-6,8-dioxabicyclo[3.2.1]octan-4-yl]oxy-tert-butyl-dimethylsilane
• 化学式: C₂₄H₅₂O₅Si₃
• 分子量: 504.93
• InChiKey: REMZCTWIJTZRPS-YMQHIKHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.91
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 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：

  1,6-anhydro-2,3,4-tri-O-tert-butyldimethylsilyl-β-D-glucopyranose 、 三苯基铝 以 二丁醚 为溶剂， 反应 23.0h， 以12%的产率得到2,3,4-tri-O-tert-butyldimethylsilyl-1-C-phenyl-β-D-glucopyranoside
  参考文献：
  名称：

  Process for the Preparation of ß-C-Aryl Glucosides

  摘要：

  本发明提供了用于立体选择性制备C-芳基葡萄糖苷的方法，这些方法可以作为合成建筑模块或药物使用，包括SGLT2抑制剂。

  公开号：

  US20140128595A1
• 作为产物：
  描述：

  1-硫代-b-甲基葡萄糖甙-4-甲基苯酯 在 吡啶 、 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 三氟甲磺酸 作用下， 以 辛醇 为溶剂， 反应 68.5h， 生成 1,6-anhydro-2,3,4-tri-O-tert-butyldimethylsilyl-β-D-glucopyranose
  参考文献：
  名称：

  “Super Armed” Glycosyl Donors:  Conformational Arming of Thioglycosides by Silylation

  摘要：

  Glycosyl donors protected with bulky silyl protective groups (tert-butyldimethylsilyl, TBS), on the 2-, 3-, and 4-OH groups were found to have superior reactivity compared with benzylated thioglucosides. The enhanced reactivity is explained by the stereoelectronic effects associated with the conformational change induced by the silylation. A TBS silylated thioglucoside donor has axial OR groups, whereas a benzylated thioglucoside has equatorial OR groups, leading to much more favorable charge-dipole interactions in the transition state. This concept could be used to create "super armed" glucosyl, mannosyl, rhamnosyl, and galactosyl donors, which could cross-couple with the armed acceptors, phenyl 2,3,4-tri-O- benzyl-beta-D-thioglucoside or phenyl 2,3,6-tri-O-benzyl-beta-D-thioglucoside, to give the corresponding armed disaccharides in good to excellent yields.

  DOI：

  10.1021/ja071955l

文献信息

• 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。
• β-Selective <i>C</i>-Arylation of Silyl Protected 1,6-Anhydroglucose with Arylalanes: The Synthesis of SGLT2 Inhibitors
  作者：Julian P. Henschke、Ping-Yu Wu、Chen-Wei Lin、Shi-Feng Chen、Pei-Chen Chiang、Chi-Nung Hsiao

  DOI：10.1021/jo502839e

  日期：2015.2.20

  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.
• Regioselectively Trisilylated Hexopyranosides through Homogeneously Catalyzed Silane Alcoholysis
  作者：Mee-Kyung Chung、Marcel Schlaf

  DOI：10.1021/ja056283i

  日期：2005.12.1

  The iridium complex [Ir(COD)(PPh3)(2)]+SbF6- reacts with tert-butyldimethylsi lane in DMA to form [IrH2(Sol)(2)(PPh3)(2)]+SbFr6-, which is an active catalyst for the regioselective di- and trisilylation of a series of representative methyl h exopyranosides, beta-1,6-anhydrohexopyranosides and 1,3,5-O-methylidene inositol. The corresponding 2,3,6- and 2,4,6-silylated glycosides are obtained in a separable mixture of 47-89% (2,3,6-isomers) and 9-25% (2,4,6-isomers) yield in a single-pot reaction. The 2,4-disilylated derivatives of mannosan, galactosan, and 1,3,5-O-methylidene inositol as well as persilylated levoglucosan are accessible in > 85% yield by this method. The homogeneous nature of the catalysts is a prerequisite for the effective di-/trisilylation, as nanoparticle colloid catalysts generated in situ from Pd-2(dba)(3) (similar to 1.5 nm average particle size) or Ru2Cl5(MeCN)(7) (similar to 0.65 nm average particle size) result in only low yields.
• Process for the Preparation of ß-C-Aryl Glucosides
  申请人：ScinoPharm Taiwan, LTD.

  公开号：US20140128595A1

  公开（公告）日：2014-05-08

  The present invention provides processes for stereoselectively preparing C-arylglucosides that can be useful as synthetic building block or drugs, including SGLT2 inhibitors.

  本发明提供了用于立体选择性制备C-芳基葡萄糖苷的方法，这些方法可以作为合成建筑模块或药物使用，包括SGLT2抑制剂。
• “Super Armed” Glycosyl Donors:  Conformational Arming of Thioglycosides by Silylation
  作者：Christian Marcus Pedersen、Lars Ulrik Nordstrøm、Mikael Bols

  DOI：10.1021/ja071955l

  日期：2007.7.1

  Glycosyl donors protected with bulky silyl protective groups (tert-butyldimethylsilyl, TBS), on the 2-, 3-, and 4-OH groups were found to have superior reactivity compared with benzylated thioglucosides. The enhanced reactivity is explained by the stereoelectronic effects associated with the conformational change induced by the silylation. A TBS silylated thioglucoside donor has axial OR groups, whereas a benzylated thioglucoside has equatorial OR groups, leading to much more favorable charge-dipole interactions in the transition state. This concept could be used to create "super armed" glucosyl, mannosyl, rhamnosyl, and galactosyl donors, which could cross-couple with the armed acceptors, phenyl 2,3,4-tri-O- benzyl-beta-D-thioglucoside or phenyl 2,3,6-tri-O-benzyl-beta-D-thioglucoside, to give the corresponding armed disaccharides in good to excellent yields.