3,7-脱水-1,2-二脱氧-4,5,6,8-四-O-(苯基甲基)-D-甘油型-D-古洛-辛-1-炔糖醇 | 168253-07-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3,7-脱水-1,2-二脱氧-4,5,6,8-四-O-(苯基甲基)-D-甘油型-D-古洛-辛-1-炔糖醇
• 英文名称: (2R,3R,4R,5S,6S)-3,4,5-Tris-benzyloxy-2-benzyloxymethyl-6-ethynyl-tetrahydro-pyran
• 英文别名: (2S,2R,3R,4R,5S)-3,4,5-tris(benzyloxy)-2-(benzyloxymethyl)-6-ethynyl-tetrahydro-2H-pyran；2,3,4,6-tetra-O-benzyl-1-deoxy-1-ethynyl-β-D-glucopyranose；1-ethynyl-2,3,4,6-tetra-O-benzyl-β-D-glucopyranose；(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)ethyne；(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)octyne；β-ethynyl 2,3,4,6-tetra-O-benzyl-glucopyranoside；2-C-(2,3,4,6-Tetra-O-benzyl-b-D-glucopyranosyl) ethyne；(2S,3S,4R,5R,6R)-2-ethynyl-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxane
• CAS: 168253-07-4
• 化学式: C₃₆H₃₆O₅
• 分子量: 548.679
• InChiKey: ODYZSGODFGXEDP-LPMXJBPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 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：

  3,7-脱水-1,2-二脱氧-4,5,6,8-四-O-(苯基甲基)-D-甘油型-D-古洛-辛-1-炔糖醇 在 吡啶 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 2,2,6,6-四甲基哌啶氧化物 、 1,3-二溴-5,5-二甲基海因 、 platinum on carbon 、 三氟化硼乙醚 、 氢气 、 乙酸酐 、 碳酸氢钠 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙硫醇 为溶剂， 120.0 ℃ 、101.33 kPa 条件下， 反应 61.5h， 生成 methyl (3S,4R,5S,6S)-3,4,5-triacetoxy-6-[2-[5-[[(2S)-2-[[(2S)-2-(9H-fluoren-9- ylmethoxycarbonylamino)-3-methylbutanoyl]amino]propanoyl]amino]-2-(hydroxymethyl)phenyl]ethyl]tetrahydropyran-2-carboxylate
  参考文献：
  名称：

  MET BCL-XL INHIBITOR ANTIBODY-DRUG CONJUGATES AND METHODS OF USE THEREOF

  摘要：

  Anti-Met antibody-drug conjugates that bind to human oncology targets are disclosed. The antibody-drug conjugates comprise a Bcl-xL inhibitor drug moiety and an anti-Met antibody or antigen-binding fragment thereof that binds the antigen target, e.g., the antigen expressed on a tumor or other cancer cells. The disclosure further relates to methods and compositions for use in the treatment of cancers by administering the antibody¬ drug conjugates provided herein. Linker-drug conjugates comprising Bcl-xL inhibitor drug moiety and methods of making same are also disclosed.

  公开号：

  WO2023225336A1
• 作为产物：
  描述：

  (2S,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)-2-((trimethylsilyl)ethynyl)tetrahydro-2H-pyran-2-ol 在 三乙基硅烷 、 三氟化硼乙醚 、 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 3,7-脱水-1,2-二脱氧-4,5,6,8-四-O-(苯基甲基)-D-甘油型-D-古洛-辛-1-炔糖醇
  参考文献：
  名称：

  Total synthesis of indole-3-acetonitrile-4-methoxy-2-C-β-d-glucopyranoside. Proposal for structural revision of the natural product

  摘要：

  吲哚-3-乙腈-4-甲氧基-2-C-β-D-葡萄糖苷（1），是一种来自蓝靛（Isatis indigotica）的新型C-糖苷，具有重要的细胞毒活性，已通过从炔基β-C-糖苷3和2-碘-3-硝基苯乙酸酯6的十步反应合成。合成中的关键步骤包括Sonogashira偶联和CuI介导的吲哚形成。合成的1的NMR光谱数据与自然产物的报告数据不同。提出了一种含有不同碳水化合物取代基的自然产物修订结构。

  DOI：

  10.1039/c2ob25821h

文献信息

• Regioselective Synthesis of 6-Alkynyl-6-Deoxy and Pseudo-C-Disaccharides Derivatives of Mannofuranose via a 5,6-Cyclic Sulfate
  作者：Thierry Gourlain、Anne Wadouachi、Daniel Beaupère

  DOI：10.1055/s-1999-3389

  日期：1999.2

  C-6 opening of a 5,6-cyclic sulfate derivative of mannofuranoside 1 with acetylenic anion generated from oct-1-yne or phenylethyne gave corresponding 6-alkynyl-6-deoxy derivatives 2 and 3 respectively. The reaction of 5,6-cyclic sulfate 1 with lithium acetylide derived from monosaccharide led to pseudo-C-disaccharide 5. A one-pot procedure was achieved using lithium acetylide in THF/HMPA, to prepare symmetric pseudo-C-disaccharide 7. This method, used with a 5,6-cyclic sulfate derivative of glucofuranose 11 with the acetylide anion derived from mannofuranose 9, gave the corresponding nonsymmetric pseudo-C-disaccharide 13.

  C-6开环反应：利用从辛-1-炔或苯乙炔生成的炔基负离子，打开甘露呋喃糖苷1的5,6-环硫酸酯衍生物，分别得到相应的6-炔基-6-脱氧衍生物2和3。5,6-环硫酸酯1与源自单糖的锂炔化物反应，形成伪C-二糖5。通过在THF/HMPA中使用锂炔化物的一锅法程序，制备了对称伪C-二糖7。该方法应用于葡萄呋喃糖11的5,6-环硫酸酯衍生物，与源自甘露呋喃糖9的炔化负离子反应，得到相应的非对称伪C-二糖13。
• Novel Carboranyl C-Glycosides for the Treatment of Cancer by Boron Neutron Capture Therapy
  作者：Lutz F. Tietze、Ulrich Griesbach、Ingrid Schuberth、Ulrich Bothe、Alberto Marra、Alessandro Dondoni

  DOI：10.1002/chem.200390148

  日期：2003.3.17

  The synthesis of the novel unprotected carboranyl C-glycosides 2 and 20-24 starting from ethynyl C-glycosides 1, 5-8, 10, and 13 is described. The new compounds are highly water-soluble and display only a very low cytotoxicity, which makes them promising candidates for use in boron neutron capture therapy for the treatment of cancer.

  描述了从乙炔基C-糖苷1、5-8、10和13开始的新型未保护的碳硼烷基C-糖苷2和20-24的合成。这些新化合物高度水溶性，并且仅显示出非常低的细胞毒性，这使其成为有望用于硼中子俘获疗法以治疗癌症的候选药物。
• Chemoenzymatic Synthesis of Triazole-Linked Glycopeptides
  作者：Floris Rutjes、Stan Groothuys、Brian Kuijpers、Peter Quaedflieg、Harlof Roelen、Roel Wiertz、Richard Blaauw、Floris van Delft

  DOI：10.1055/s-2006-942509

  日期：——

  Triazole-linked glycopeptides are prepared by C-terminal elongation of glycoamino acids with proteinogenic amino acids following a chemical or enzymatic coupling protocol. Two orthogonal routes for a chemoenzymatic strategy were explored, involving a click-reaction before amide bond formation or in reverse order. It was found that enzymatic peptide coupling under the influence of alcalase proceeds cleanly and in high yields, while the resulting dipeptides can be efficiently clicked to acetylene- or azide-containing sugars.

  三氮唑联接的糖肽通过糖氨基酸的C端延伸，与蛋白质氨基酸按照化学或酶促耦合协议制备。探索了两条正交路径的化学酶促策略，涉及在酰胺键形成之前或顺序相反的点击反应。研究发现，在碱性蛋白酶的影响下，酶促肽耦合过程顺利进行且产率较高，同时所得的二肽可以高效地与含有炔烃或叠氮的糖发生点击反应。
• Facile synthesis of 1,2,3-triazole analogs of SGLT2 inhibitors by ‘click chemistry’
  作者：Lan-Tao Li、Li-Fei Zhou、Yan-Jun Li、Juan Huang、Rui-Hua Liu、Bin Wang、Peng Wang

  DOI：10.1016/j.bmcl.2011.10.062

  日期：2012.1

  Novel analogs of SGLT2 inhibitors containing the 1,2,3-triazole motif were designed and synthesized for urinary glucose excretion evaluation. The C-glucosides with triazole aglycone can be easily constructed by click chemistry. Most of the synthesized compounds increased urinary glucose excretion and demonstrated inhibition of glucose transport.

  设计并合成了含有1,2,3-三唑基序的SGLT2抑制剂的新型类似物，用于尿葡萄糖排泄评估。带有三唑糖苷配基的C-葡萄糖苷可以通过点击化学轻松地构建。大多数合成的化合物会增加尿中葡萄糖的排泄，并显示出对葡萄糖转运的抑制作用。
• Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase
  作者：Sándor Kun、Éva Bokor、Ádám Sipos、Tibor Docsa、László Somsák

  DOI：10.3390/molecules23030666

  日期：——

  ,2,3-triazoles were prepared by copper catalyzed azide-alkyne cycloadditions between O-perbenzylated or O-peracetylated β-d-glucopyranosyl ethynes and aryl azides. 1-β-d-Gluco-pyranosyl-4-phenyl imidazole was obtained in a glycosylation of 4(5)-phenylimidazole with O-peracetylated α-d-glucopyranosyl bromide. C-β-d-Glucopyranosyl-N-substituted-tetrazoles were synthesized by alkylation/arylation of O-perbenzoylated

  本研究的目的是拓宽糖原磷酸化酶的C-和N-β-d-吡喃葡萄糖基唑类抑制剂的结构-活性关系。通过在O-过苄基化或O-过乙酰化的β-d-吡喃葡萄糖基乙炔与芳基叠氮化物之间进行铜催化的叠氮化物-炔烃环加成反应，制得1-芳基-4-β-d-葡萄糖-吡喃葡萄糖基-1,2,3-三唑。在4-（5）-苯基咪唑与O-过乙酰化的α-d-吡喃葡萄糖基溴化物的糖基化反应中获得了1-β-d-葡糖基-吡喃基-4-苯基咪唑。通过O-过苯甲酰化的5-β-d-吡喃葡萄糖基-四唑的烷基化/芳基化反应或由2,6-脱水庚糖甲苯磺酰and和槟榔重氮盐合成C-β-d-戊二糖基-N-取代的四唑。将5-取代的四唑通过O-过乙酰化的α-d-吡喃葡萄糖基溴化物糖基化，得到N-β-d-吡喃葡萄糖基-C取代的四唑。标准脱保护得到测试化合物，其针对兔肌肉糖原磷酸化酶b进行了测定。多数化合物被证明是无活性的，最好的抑制剂是2-β-d-吡喃葡萄糖基-5-苯基四唑（IC50