methyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranoside | 412926-36-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranoside
• 英文别名: [(2R,3S,4R,5R,6R)-5-acetamido-4-acetyloxy-2-(hydroxymethyl)-6-methoxyoxan-3-yl] acetate
• CAS: 412926-36-4
• 化学式: C₁₃H₂₁NO₈
• 分子量: 319.312
• InChiKey: JDSVIVDKJNTJCW-SYLRKERUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranoside 在 palladium on activated charcoal sodium tetrahydroborate 、 pyridine-SO3 complex 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 73.83h， 生成 methyl 2-acetamido-2,4-dideoxy-β-D-xylo-hexopyranoside
  参考文献：
  名称：

  Synthesis and biological evaluation of a radiolabeled analog of methyl 2-acetamido-2,4-dideoxy-β-d-xylo-hexopyranoside directed towards influencing cellular glycosaminoglycan biosynthesis

  摘要：

  Two methods are presented for the synthesis or methyl 2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranoside. The first method employs the Barton-McCombie deoxygenation methodology, and the second method utilizes an oxidation-beta-elimination methodology that allows for the incorporation of hydrogen isotopes into the title compound. Hence, methyl 2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranoside (4) and methyl 2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranoside-6-t (14) were synthesized and evaluated for their ability to inhibit hepatocyte, cell-surface glycosaminoglycan biosynthesis and to incorporate a [H-3] radiolabel into isolated glycosaminoglycans, respectively. Compound 4, at a concentration of 1.0 mM, demonstrated a reduction of D-[H-3]glucosamine and [S-35]sulfate incorporation into isolated glycosaminoglycans by 69 and 59%, of the control cultures, respectively. At 10 and 20 mM, 4 demonstrated a maximum inhibition of incorporation of both radiolabels to approximately 10% of the control cultures. Compound 14 demonstrated a maximum incorporation of a [H-3] radiolabel into isolated cell-surface glycosaminoglycans at 10 and 20 mM. The mechanism of inhibition of glycosaminoglycan biosynthesis is due, in part, to the incorporation of a 4-deoxy moiety into glycosaminoglycan chains resulting in premature chain termination. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(01)00285-3
• 作为产物：
  描述：

  甲基2-乙酰氨基-2-脱氧-BETA-D-吡喃葡萄糖苷 在 甲酸 作用下， 以 吡啶 、 乙醚 为溶剂， 反应 99.5h， 生成 methyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  Synthesis and biological evaluation of a radiolabeled analog of methyl 2-acetamido-2,4-dideoxy-β-d-xylo-hexopyranoside directed towards influencing cellular glycosaminoglycan biosynthesis

  摘要：

  Two methods are presented for the synthesis or methyl 2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranoside. The first method employs the Barton-McCombie deoxygenation methodology, and the second method utilizes an oxidation-beta-elimination methodology that allows for the incorporation of hydrogen isotopes into the title compound. Hence, methyl 2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranoside (4) and methyl 2-acetamido-2,4-dideoxy-beta-D-xylo-hexopyranoside-6-t (14) were synthesized and evaluated for their ability to inhibit hepatocyte, cell-surface glycosaminoglycan biosynthesis and to incorporate a [H-3] radiolabel into isolated glycosaminoglycans, respectively. Compound 4, at a concentration of 1.0 mM, demonstrated a reduction of D-[H-3]glucosamine and [S-35]sulfate incorporation into isolated glycosaminoglycans by 69 and 59%, of the control cultures, respectively. At 10 and 20 mM, 4 demonstrated a maximum inhibition of incorporation of both radiolabels to approximately 10% of the control cultures. Compound 14 demonstrated a maximum incorporation of a [H-3] radiolabel into isolated cell-surface glycosaminoglycans at 10 and 20 mM. The mechanism of inhibition of glycosaminoglycan biosynthesis is due, in part, to the incorporation of a 4-deoxy moiety into glycosaminoglycan chains resulting in premature chain termination. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(01)00285-3

文献信息

• <i>o</i>-(<i>p</i>-Methoxyphenylethynyl)phenyl Glycosides: Versatile New Glycosylation Donors for the Highly Efficient Construction of Glycosidic Linkages
  作者：Yang Hu、Ke Yu、Li-Li Shi、Lei Liu、Jing-Jing Sui、De-Yong Liu、Bin Xiong、Jian-Song Sun

  DOI：10.1021/jacs.7b07020

  日期：2017.9.13

  bestows on the new glycosyl donors enhanced stability compared to their thioglycoside counterparts toward activation conditions applied for glycosyl trichloroacetimidate (TCAI) and o-alkynylbenzoate (ABz) donor. Thus, MPEPs can also be utilized in the selective one-pot glycosylation strategy, as exemplified by the syntheses of oligosaccharides via successive glycosylations with glycosyl TCAI, ABz, and

  建立了一种使用邻（对甲氧基苯基乙炔基）苯基 (MPEP) 糖苷的新型基于炔烃活化的糖基化方案。糖基 MPEP 供体是货架稳定的，可以通过相应的邻碘苯基 ​​(IP) 糖苷通过 Sonogashira 反应有效地制备。IP 糖苷的出色稳定性及其向 MPEP 糖苷的有效转化极大地促进了 MPEP 糖基供体和 IP 糖基受体的合成。此外，他们使 MPEP 糖基化方案适用于潜在活性寡糖和糖缀合物合成策略，以 IP 糖苷为潜在形式，MPEP 糖苷为活性形式，如肺炎链球菌 3 型三糖的高效制造所示。MPEP 糖苷的酚糖苷性质赋予新的糖基供体与硫糖苷对应物相比，对应用于糖基三氯乙酰亚胺 (TCAI) 和邻炔基苯甲酸酯 (ABz) 供体的活化条件具有更高的稳定性。因此，MPEP 也可用于选择性一锅糖基化策略，例如通过连续糖基化以糖基 TCAI、ABz 和 EPMP 作为供体合成寡糖。尽管与硫糖苷供体共享相同的促进条件，但无气味的起始材料
• Zirconium-Catalyzed Hydroalumination of C═O Bonds: Site-Selective De-<i>O</i>-acetylation of Peracetylated Compounds and Mechanistic Insights
  作者：Thibaut Courant、Marine Gavel、Romain M. Q. Renard、Vincent Gandon、Antoine Y. P. Joosten、Thomas Lecourt

  DOI：10.1021/acs.joc.1c00060

  日期：2021.7.16

  An unprecedented hydroalumination of C ═ O bonds catalyzed by zirconocene dichloride is reported herein and applied to the site-selective deprotection of peracetylated functional substrates. A mixed metal hydride, with 1:1 zirconium/aluminum stoichiometry, is also shown to be the reductive species. A catalytic cycle is finally proposed for this transformation with no precedent in the field of zirconium

  本文报道了一种前所未有的由二氯化锆催化的 C = O 键的氢铝化，并应用于全乙酰化功能底物的位点选择性脱保护。具有 1:1 锆/铝化学计量比的混合金属氢化物也显示为还原物质。最终为这种转化提出了一种催化循环，这在锆催化领域是没有先例的。
• Chemoenzymatic Synthesis of Glycoconjugates Mediated by Regioselective Enzymatic Hydrolysis of Acetylated 2-Amino Pyranose Derivatives
  作者：Changping Zheng、Teodora Bavaro、Sara Tengattini、Andrea Gualla Mascherpa、Matthieu Sollogoub、Yongmin Zhang、Marco Terreni

  DOI：10.1002/ejoc.201900382

  日期：2019.6.16

  A chemoenzymatic approach, mediated by acetyl xylan esterase (AXE) from Bacillus pumilus and Candida rugosa lipase (CRL), permits the concise synthesis of neo‐glycoproteins and glycosphingolipids, respectively.

  一种化学酶方法，由短小芽孢杆菌的乙酰木聚糖酯酶（AXE）和皱纹念珠菌脂肪酶（CRL）介导，可以分别合成新糖蛋白和糖鞘脂。
• Regio- and Chemoselective Deprotection of Primary Acetates by Zirconium Hydrides
  作者：Marine Gavel、Thibaut Courant、Antoine Yvan Philippe Joosten、Thomas Lecourt

  DOI：10.1021/acs.orglett.8b03947

  日期：2019.4.5

  A combination of DIBAL-H and Cp2ZrCl2 is shown to promote the regioselective cleavage of primary acetates on a broad scope of substrates, ranging from carbohydrates to terpene derivatives, with a high tolerance toward protecting groups and numerous functionalities found in natural products and bioactive compounds. Apart from providing highly valuable building blocks in only two steps from biosourced raw materials, this selective de-O-acetylation should also be strongly helpful to solve selectivity issues in organic synthesis.
• Matrix metalloproteinase-12 inhibitors: synthesis, structure-activity relationships and intestinal absorption of novel sugar-based biphenylsulfonamide carboxylates
  作者：Doretta Cuffaro、Caterina Camodeca、Felicia D'Andrea、Eugenia Piragine、Lara Testai、Vincenzo Calderone、Elisabetta Orlandini、Elisa Nuti、Armando Rossello

  DOI：10.1016/j.bmc.2018.10.024

  日期：2018.12

  MMP-12 is a validated target in pulmonary and cardiovascular diseases. The principal obstacles to clinical development of MMP-12 inhibitors are an inadequate selectivity for the target enzyme and a poor water solubility, with consequent poor oral bioavailability. We recently reported a new class of sugar-based arylsulfonamide carboxylates with a nanomolar activity for MMP-12, a good selectivity and an improved water solubility. In this study, we designed and synthesized new derivatives to characterize the structure-activity relationship (SAR) within this class of glycoconjugate inhibitors. All the new derivatives were tested on human recombinant MMP-12 and MMP-9 in order to evaluate their affinity and the selectivity for the target enzyme. Among them, the four most promising compounds were selected to assess their intestinal permeability using an ex vivo everted gut sac model. Given the high polarity and structural similarity to glucose, compound 3 was demonstrated to cross the intestinal membrane by using the facilitative GLUT2 transport.