methyl 5-acetamido-8,9-O-isopropylidene-2,3,5-trideoxy-D-glycero-D-galacto-non-2-enopyranosonate | 108999-10-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-acetamido-8,9-O-isopropylidene-2,3,5-trideoxy-D-glycero-D-galacto-non-2-enopyranosonate
• 英文别名: methyl (2R,3R,4S)-3-acetamido-2-[(S)-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-hydroxymethyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 108999-10-6
• 化学式: C₁₅H₂₃NO₈
• 分子量: 345.35
• InChiKey: NDLKMQLQMWVTFN-VECUTGAWSA-N

物化性质

• 沸点：
  564.5±50.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 5-acetamido-8,9-O-isopropylidene-2,3,5-trideoxy-D-glycero-D-galacto-non-2-enopyranosonate 在 吡啶 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成
  参考文献：
  名称：

  Synthesis of Ganglioside GD3 and its Comparison with Bovine GD3 with Regard to Oligodendrocyte Apoptosis Mitochondrial Damage

  摘要：

  2,3-Dehydroneuraminic acid derivative 5 was transformed in five efficient steps into sialyl donor 2, which has a phenylthio group on the beta-side of the 3-position for anchimeric assistance and a diethyl phosphite residue as leaving group at the anomeric carbon. The known GM3 intermediate 10 was transformed into the 4b,4c,8c-O-unprotected acceptor 3, which was then allowed to react with 2 by using TMSOTf as catalyst and acetonitrile as solvent to afford the desired tetrasaccharide 12, which has an alpha(2-8)-linkage between two neuraminic acid residues. Removal of the phenylthio group gave intermediate 13, which was transformed into O-tetraosyl trichloroacetimidate 16 as glycosyl donor. Application of the azidosphingosine glycosylation procedure furnished GD3 (1) in high overall yield. Comparison of synthetic GD3 with bovine-brain-derived GD3 showed that there were similar effects in GD3-triggered uncoupling of mitochondrial respiration and in induction of apoptosis in oligodendrocytes.

  DOI：

  10.1002/1521-3765(20010518)7:10<2178::aid-chem2178>3.0.co;2-e
• 作为产物：
  描述：

  N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester 在 sodium methylate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 4.5h， 生成 methyl 5-acetamido-8,9-O-isopropylidene-2,3,5-trideoxy-D-glycero-D-galacto-non-2-enopyranosonate
  参考文献：
  名称：

  合成和评估作为人副流感病毒3型唾液酸酶活性抑制剂的4-O-烷基化的2-deoxy-2,3-didehydro-N-乙酰神经氨酸衍生物。

  摘要：

  来自新城疫病毒的副粘病毒表面糖蛋白血凝素神经氨酸酶（HN）的X射线晶体结构被用作模板来设计人类副流感病毒3型（hPIV-3）的HN抑制剂。发现从8,9-O-异亚丙基化-Neu5Ac2en1Me获得的2-脱氧-2,3-二氢-N-乙酰神经氨酸的4-O-烷基化衍生物可抑制hPIV-的唾液酸酶（神经氨酸酶）活性。 3（菌株C243）在3-30μM的范围内。与母体4-羟基化合物相比，这具有可比或更高的活性。

  DOI：

  10.1016/j.bmcl.2006.12.105

文献信息

• A Stereospecific Synthesis of β-Glycosides of<i>N</i>-Acetylneuraminic Acid and Secondary Alcohols
  作者：Kaoru Okamoto、Tadao Kondo、Toshio Goto

  DOI：10.1246/cl.1986.1449

  日期：1986.9.5

  Glycosylation of secondary alcohols such as cholesterol, methyl 2,4,6-tri-O-benzylgalactopyranoside, and 2-deoxy-2,3-dehydro-NeuAc methyl ester with a new glycosyl donor, 2β,3α-dibromo-2-deoxy-NeuAc methyl ester, selectively gave the corresponding β-glycosides in high yields. The 3α-bromo-glycosides were debrominated with tri-n-butylstannane to the corresponding glycosides, which were deprotected to

  仲醇如胆固醇、甲基 2,4,6-tri-O-benzylgalactopyranoside 和 2-deoxy-2,3-dehydro-NeuAc 甲酯与新的糖基供体 2β,3α-dibromo-2-deoxy 的糖基化-NeuAc 甲酯，选择性地以高产率得到相应的 β-糖苷。3α-溴-糖苷用三正丁基锡烷脱溴为相应的糖苷，将其脱保护得到具有β-NeuAc的游离糖苷。
• 2-Deoxy-2,3-didehydro-N-acetylneuraminic acid analogs structurally modified by thiocarbamoylalkyl groups at the C-4 position: Synthesis and biological evaluation as inhibitors of human parainfluenza virus type 1
  作者：Kiyoshi Ikeda、Kazuki Sato、Reiko Nishino、Shinya Aoyama、Takashi Suzuki、Masayuki Sato

  DOI：10.1016/j.bmc.2008.05.055

  日期：2008.7

  n 3 has strong inhibitory activity toward human parainfluenza virus type 1 (hPIV-1) sialidase compared with the parent Neu5Ac2en 2. We synthesized analogs having thiocarbamoylethyl- 4 and thiocarbamoylpropyl group 5 at the C-4 position of 2. The inhibition degrees of 4 and 5 were weaker than that of thiocarbamoylmethyl analog 3, indicating a remarkable effect of the carbon chain length in thiocarbamoylalkyl

  与亲本Neu5Ac2en 2相比，4-O-硫代氨基甲酰基甲基-Neu5Ac2en 3对人副流感病毒1型（hPIV-1）唾液酸酶具有较强的抑制活性。 4和5的抑制程度比硫代氨基甲酰基甲基类似物3的抑制度弱，表明C-4位的硫代氨基甲酰基烷基的碳链长度对hPIV-1唾液酸酶的抑制活性有显着影响。
• Useful Sialic Acid Modifications Catalyzed by Palladium
  作者：Chih-Wei Chang、Stéphanie Norsikian、Jean-Marie Beau

  DOI：10.1002/chem.200900093

  日期：2009.5.18

  A regio‐ and stereocontrolled solution for a selective modification at the C‐2 or C‐4 position of N‐acetylneuraminic acid involves the use of allylic substitution catalyzed by palladium. As illustrated in the scheme, regioselective malonylation is under the strict influence of the ligands associated with the allylpalladium complex.

  在N-乙酰神经氨酸的C-2或C-4位置进行选择性修饰的区域和立体控制溶液涉及使用钯催化的烯丙基取代。如该方案所示，区域选择性丙二酰化作用在与烯丙基钯配合物相关的配体的严格影响下。
• Regio- and Stereocontrolled Palladium-Catalyzed Allylic Substitution on N-Acetylneuraminic Acid Derivatives
  作者：Chih-Wei Chang、Stéphanie Norsikian、Regis Guillot、Jean-Marie Beau

  DOI：10.1002/ejoc.200901452

  日期：2010.4

  stoichiometric preparation and study of the highly probable complexes involved in the catalytic reaction. Reactions of this type were also applied to other nucleophiles for the construction of C-C, C-N, and C-O bonds, leading to the major formation of the C-4 regioisomers. The selective transformation of some of the substitution products provided easy access to a variety of modified sialic acid derivatives

  已开发出一种高效的区域选择性和立体选择性钯催化烯丙基取代 N-乙酰神经氨酸 (Neu5Ac2en) 的 2,3-不饱和衍生物的方法。我们表明烯丙基化反应的效率取决于起始材料上合适的保护基团，并且丙二酸钠阴离子作为亲核试剂，区域选择性可以通过与钯配合物相关的配体的性质进行微调。这些结果可以通过化学计量制备和催化反应中涉及的极可能配合物的研究来解释。这种类型的反应也应用于其他亲核试剂以构建 CC、CN 和 CO 键，导致 C-4 区域异构体的主要形成。
• A light- and heat-driven glycal diazidation approach to nitrogenous carbohydrate derivatives with antiviral activity
  作者：Huan He、Ruiyuan Cao、Ruidi Cao、Xiao-Yu Liu、Wei Li、Di Yu、Yuexiang Li、Miaomiao Liu、Yanmei Wu、Pingzhou Wu、Jin-Song Yang、Yunzheng Yan、Jingjing Yang、Zhi-Bing Zheng、Wu Zhong、Yong Qin

  DOI：10.1039/d0ob01172j

  日期：——

  The aminated mimetics of 2-keto-3-deoxy-sugar acids such as the anti-influenza clinical drugs oseltamivir (Tamiflu) and zanamivir (Relenza) are important bioactive molecules. Development of synthetic methodologies for accessing such compound collections is highly desirable. Herein, we describe a simple, catalyst-free glycal diazidation protocol enabled by visible light-driven conditions. This new method

  2-keto-3-deoxy-sugar 酸的胺化模拟物，如抗流感临床药物奥司他韦（达菲）和扎那米韦（Relenza）是重要的生物活性分子。开发用于访问此类化合物集合的合成方法是非常可取的。在这里，我们描述了一种由可见光驱动条件启用的简单、无催化剂的糖基二叠氮化协议。这种新方法既不需要酸助剂也不需要过渡金属催化剂，并且在环境温度下可在 1-2 小时内完成。值得注意的是，热条件也可以促进所需的转化，尽管与光诱导条件相比效率较低。通过利用这种温和且可扩展的方法，已将不同的糖酸衍生的糖模板转化为一系列 2,3-二叠氮基碳水化合物类似物，