methyl 4,7,8,9-tetra-O-acetyl-2,6-anhydro-5-azido-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate | 136737-08-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 4,7,8,9-tetra-O-acetyl-2,6-anhydro-5-azido-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate
• 英文别名: methyl (2R,3R,4S)-4-acetyloxy-3-azido-2-[(1S,2R)-1,2,3-triacetyloxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 136737-08-1
• 化学式: C₁₈H₂₃N₃O₁₁
• 分子量: 457.394
• InChiKey: FIGIIARLODVTPO-IIHMKKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  32
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  155
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl 4,7,8,9-tetra-O-acetyl-2,6-anhydro-5-azido-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate 在 甲醇 、 sodium methylate 作用下， 生成 methyl 2,6-anhydro-5-azido-3,5-dideoxy-D-glycero-α-D-galacto-non-2-enonate
  参考文献：
  名称：

  硫唾液酸苷和 2,3-脱氢-5-N-乙酰神经氨酸 (DANA) 的 C5-叠氮衍生物的轻松合成

  摘要：

  神经氨酸（Neu5Ac，又称唾液酸）是糖蛋白和糖脂中发现的重要单糖，在调节生理功能和病理状态中发挥着重要作用。唾液酸聚糖的研究受益于与聚糖链中的神经氨酸相互作用并修饰其的蛋白质和酶的糖模拟探针和抑制剂的开发。需要高产率获取唾液酸苷中间体的方法来促进新靶标的设计。在这里，我们报道了使用温和的方法对 C5-乙酰胺基官能团进行脱保护，然后使用重氮基转移试剂合成 C5-叠氮基硫唾液酸苷。我们研究了两种重氮转移策略并比较了它们的产率和乙酸盐保护基团的耐受性。还对通常用于生成神经氨酸酶（唾液酸酶）抑制剂的2,3-脱氢-5- N-乙酰神经氨酸（DANA）支架进行了相同的方法和比较。我们发现硫唾液酸苷和 DANA 的 C5-叠氮衍生物可以通过五步或六步生产，产率分别高达 76% 和 83%。本研究中比较的重氮转移试剂是三氟甲磺酰叠氮化物（TfN 3 ）和咪唑-1-磺酰叠氮化物（ImzSO 2 N 3 ）。

  DOI：

  10.1016/j.carres.2023.109013
• 作为产物：
  描述：

  (2S,4S,5R,6R)-5-Amino-4-hydroxy-2-p-tolylsulfanyl-6-((1R,2R)-1,2,3-trihydroxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester 在 吡啶 、 甲醇 、 4-二甲氨基吡啶 、 N-碘代丁二酰亚胺 、 三氟甲磺酸 、 triflic azide 作用下， 以 二氯甲烷 、 二氯甲烷-D2 、 乙腈 为溶剂， 反应 39.08h， 生成 methyl 4,7,8,9-tetra-O-acetyl-2,6-anhydro-5-azido-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate
  参考文献：
  名称：

  Donor‐Reactivity‐Controlled Sialylation Reactions

  摘要：

  AbstractAlthough tremendous efforts have been made for the efficient preparation of sialosides, controlling the stereochemical outcome of sialylation reaction still remains one of the most challenging tasks due to the unique chemical structure of sialic acid. We developed a new strategy to statistically analyze the stereoselectivity of sialylation reactions on six types of p‐tolyl thiosialosides in NIS/TfOH system using Relative Reactivity Value (RRV) as the indicator. Analysis of the reaction mechanism showed the formation of the relatively stable glycosyl bromide and glycosyl chloride intermediates from halide‐ and triflate‐containing promotors in the absence of an acceptor. We found that the α/β‐stereoselectivity, yields, and intermediate changes were associated with their donor reactivity. These findings enable to tailor the most suitable building blocks for stereo‐controlled sialylation reactions.

  DOI：

  10.1002/ejoc.202100718

文献信息

• Studies on the sialylation of galactoses with different C-5 modified sialyl donors
  作者：Jianzhi Gong、Han Liu、John M. Nicholls、Xuechen Li

  DOI：10.1016/j.carres.2012.08.007

  日期：2012.11

  Synthetic sialylated glycans provide useful tools to study carbohydrate-mediated biological recognition; however chemical sialylation is the most challenging practice in preparative carbohydrate chemistry, which is often associated with low yields and poor stereoselectivity. Herein, we conducted extensive studies on sialylation with five types of 5-N-modified sialyl donors and four types of galactosyl acceptors. Our studies have shown that a good combination between the donor and the acceptor seems necessary to achieve high yield and stereoselectivity. None of the donors or acceptors showed 'universal' utility toward the sialylation reaction. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthetic study of 3-fluorinated sialic acid derivatives
  作者：Katsuhiko Suzuki、Shusaku Daikoku、Sang-Hyun Son、Yukishige Ito、Osamu Kanie

  DOI：10.1016/j.carres.2014.12.010

  日期：2015.4

  Sialic acid derivatives, analogs, and their conjugates are expected to be pharmaceutical candidates such as anti-influenza drugs and also useful probes for investigating the biological role of glycoconjugates. Derivatives of 3-fluorinated sialic acid (3-F-Sia) have been found to be excellent probes in investigating functions and mechanisms of a series of proteins. Here, we describe the syntheses of 3-F-Sia derivatives, which are useful in making biologically important conjugate probes. A practical method for the construction of 3-fluorinated sialosides based on the stereoselective formation of the corresponding anomeric O-trimethylsilyl ether and their nucleophilic attack by an alkyl halide, an allyl halide in particular, was developed. In addition, details of the synthesis of cytidine monophosphate (CMP)-3-F-Sia bearing a fluorescent tag, which has been proven to show dual functions as a substrate of CMP-sialic acid transporter (CST) and an inhibitor of sialyltransferase (STase), are described. (C) 2015 Elsevier Ltd. All rights reserved.
• Influence of protecting groups on O- and C-glycosylation with neuraminyl and ulosonyl dibutylphosphates
  作者：Riku Ogasahara、Shuay Abdullayev、Vikram A. Sarpe、Appi Reddy Mandhapati、David Crich

  DOI：10.1016/j.carres.2020.108100

  日期：2020.10

  The adamantanyl thioglycosides of 5-isothiocyano and 5-azido 5-desamino-4,7,8,9-tetra-O-acetylneuraminic acid methyl ester were converted into the corresponding dibutyl phosphates, which proved to be excellent alpha-selective donors for O-sialidation with a range of typical acceptors, and good donors for reaction with allyltributylstannane, albeit without significant anomeric selectivity. In the KDN series the dibuylphosphate derived from a donor carrying a 4,5-cyclic carbonate protecting group afforded the corresponding C-glycoside with excellent alpha-selectivity on activation in the presence of allyltributylstannane, whereas the corresponding donor carrying acetate esters at the 4and 5-positions was unselective. Overall, it is revealed that while the strongly electron-withdrawing isothiocyanato and azido groups are sufficient to promote highly alpha-selective O-sialidation, they are inadequate when faced with less reactive nucleophiles when mixtures of anomers are obtained.
• 2,3-Didehydro-2-deoxysialic acids structurally varied at C-5 and their behaviour towards the sialidase from Vibrio cholerae
  作者：Erwin Schreiner、Erich Zbiral、Reinhard G. Kleineidam、Roland Schauer

  DOI：10.1016/0008-6215(92)84150-q

  日期：1992.9

  2,3-Didehydro-2-deoxy-N-trifluoroacetylneuraminic acid (5-trifluoroacetyl-Neu2en) (3) has been synthesised from Neu5Ac2en (1) by hydrazinolysis, to give Neu2en (2), followed by N-trifluoroacetylation. 2,3-Didehydro-2,3-dideoxy-D-glycero-D-galacto-2-nonulopyranoson ic acid (Kdn2en, 8) and 5-azido-2,3-didehydro-2,3,5-trideoxy-D-glycero-D-galacto-2-nonu lopyranosonic acid (5-azido-5-deoxy-Kdn2en, 9) have been prepared from the acetylated methyl esters of Kdn (4) and 5-azido-5-deoxy-Kdn (5) via Zemplén saponification. The behaviour of the above 2,3-didehydro-2-deoxysialic acids towards Vibrio cholerae sialidase has been investigated.
• Synthesis of a useful lauryl thioglycoside of sialic acid and its application
  作者：Koji Matsuoka、Tomotsune Onaga、Tomonori Mori、Jun-Ichi Sakamoto、Tetsuo Koyama、Nobuo Sakairi、Ken Hatano、Daiyo Terunuma

  DOI：10.1016/j.tetlet.2004.10.105

  日期：2004.12

  An efficient synthesis of a useful thioglycosyl donor 2 was accomplished directly from known peracetylated sialic acid methvl ester and 1-dodecanethiol (lauryl mercaptan) in the presence of BF3-OEt2. The reactivities of the lauryl glycosides for glycosidation by means of TMSOTf as a convenient promoter were investigated, and the lauryl thioglycoside showed satisfactory activities. Further transformation of the lauryl glycoside was also attempted to give a 5-azide analogue 14 of the sialic acid, which was also reacted with a secondary alcohol in the presence of TMSOTf to give known glycoside 15 in high yield. (C) 2004 Elsevier Ltd. All rights reserved.