methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-2-chloro-2,3-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate | 139110-77-3

• 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 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-2-chloro-2,3-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate
• 英文别名: methyl 4,5,7,8,9-penta-O-acetyl-2-chloro-2,3-dideoxy-D-glycero-β-D-galacto-2-nonulopyranosonate；methyl 4,5,7,8,9-penta-O-acetyl-2-chloro-2,3-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate；3-deoxy-D-glycero-D-galacto-non-2-ulopyranosonyl chloride；methyl (2R,4S,5R,6R)-4,5-diacetyloxy-2-chloro-6-[(1R,2R)-1,2,3-triacetyloxypropyl]oxane-2-carboxylate
• CAS: 139110-77-3
• 化学式: C₂₀H₂₇ClO₁₃
• 分子量: 510.88
• InChiKey: CKXGSJPWXYVJKZ-DCDDNHAVSA-N

物化性质

• 沸点：
  516.2±50.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  167
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-2-chloro-2,3-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate 在 palladium on activated charcoal 吡啶 、 4-二甲氨基吡啶 、 氢气 、 碘 、 sodium methylate 、 溶剂黄146 作用下， 以 吡啶 、 甲醇 、 丙酮 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 77.0h， 生成 methyl (methyl 4,5,7,8-tetra-O-acetyl-3,9-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid)onate
  参考文献：
  名称：

  THE SYNTHESIS OF C-9 MODIFIED DERIVATIVES OF THE α-METHYL GLYCOSIDE OF KDN METHYL ESTER

  摘要：

  The synthesis of a range of C-9 substituted derivatives of the cc-methyl glycoside of KDN methyl ester (2) is reported. 9-Deoxy-9-iodo, 9-deoxy-9 thioacetyl and 9-azido-9-deoxy derivatives (compounds 10, 12 and 13) were all prepared from the corresponding 9-O-tosylate 8. Catalytic hydrogenation of 10 and 13 results in reduction to give the 9-deoxy and 9-amino-9-deoxy derivatives 20 and 15, respectively. Further derivatisation of the amine 15 into compounds 17 and 18 was achieved via standard acylation procedures.

  DOI：

  10.1081/car-100103960
• 作为产物：
  描述：

  methyl (2,4,5,7,8,9-hexa-O-acetyl-3-deoxy-D-glycero-β-D-galacto-2-nonulopyran-ose)onate 在 盐酸 、 乙酰氯 作用下， 生成 methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-2-chloro-2,3-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate
  参考文献：
  名称：

  Schreiner, Erwin; Zbiral, Erich, Liebigs Annalen der Chemie, 1990, # 6, p. 581 - 586

  摘要：

  DOI：

文献信息

• Structurally homologous sialidases exhibit a commonality in reactivity: Glycoside hydrolase-catalyzed hydrolysis of Kdn-thioglycosides
  作者：Ali Nejatie、Oluwafemi Akintola、Elizabeth Steves、Saeideh Shamsi Kazem Abadi、Margo M. Moore、Andrew J. Bennet

  DOI：10.1016/j.bioorg.2020.104484

  日期：2021.1

  of these substrates were hydrolyzed by the A. fumigatus enzyme, although M. viridifaciens sialidase-catalyzed the hydrolysis of these Kdn thioglycosides with higher catalytic efficiencies (kcat/Km). We also tested an enzyme that was evolved from MvNA to improve its activity against Kdn glycosides (Glycobiology 2020, 30, 325). All three enzymes catalyzed the hydrolysis of the four most reactive Kdn thioglycosides

  烟曲霉是侵袭性曲霉病的主要病原体之一，这是一种影响免疫功能低下个体的常致死真菌病。A. fumigatus产生一种唾液酸酶，可从糖缀合物中裂解九碳碳水化合物 Kdn。这种酶在A. fumigatus致病性中起关键作用，因此是开发新疗法的目标。为了了解这种 Kdnase 的反应性，并对其催化活性进行灵敏和选择性的测定，我们确定了这种酶是否与其紧密结构同源物绿色小单孢菌产生的分泌唾液酸酶一样，可以有效地水解硫糖苷底物。我们合成了一组七芳基 2-硫代-d -甘油-α- d -半乳糖-non-2-ulopyranosonides 并测量烟曲霉Kdnase 对这些底物的活性。这些底物中的四种被烟曲霉酶水解，尽管M. viridifaciens唾液酸酶以更高的催化效率 ( k cat / K m )催化这些 Kdn 硫糖苷的水解。我们还测试了一种从Mv NA进化而来的酶，以提高其对 Kdn 糖苷的活性
• Novel practical synthesis of Kdn2en and its C-4 nitrogen-modified derivatives
  作者：Xue-Long Sun、Noriko Sato、Toshitsugu Kai、Kimio Furuhata

  DOI：10.1016/s0008-6215(99)00236-0

  日期：1999.1

  A practical synthesis of Kdn2en and 4-amino-4-deoxy-Kdn2en has been achieved via a key intermediate, methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-3-deoxy-D-glycero-D-galacto-non-2- enonate, which has been prepared from Kdn in three steps in 91% overall yield.

  已通过关键中间体甲基4,5,7,8,9-戊-O-乙酰基-2,6-脱水3-脱氧-甲基完成了Kdn2en和4-氨基-4-脱氧-Kdn2en的实用合成。 D-甘油-D-半乳糖-非-2-烯酸酯，它是由Kdn分三步制备的，总产率为91％。
• A Mechanistic Study on the Non‐enzymatic Hydrolysis of Kdn Glycosides
  作者：Ali Nejatie、Cinzia Colombo、Benyamin Hakak‐Zargar、Andrew J. Bennet

  DOI：10.1002/ejoc.202101387

  日期：2022.1.27

  neuraminidase activity and selectivity, is shown to increase when the C5-substituent becomes sterically smaller (lower A-value), while electronic effects (Taft values) are less important for these hydrolysis reactions.

  4-硝基苯基唾液酸苷是用于评估神经氨酸酶活性和选择性的底物，当 C5 取代基在空间上变小（较低的 A 值）时，其内在反应性会增加，而电子效应（Taft 值）对这些水解反应。
• Synthesis of Fluorescent 4-Methyl-7-thiocoumaryl S-Glycosides of Sialic Acid.
  作者：Makoto TANAKA、Toshitsugu KAI、Xue-Long SUN、Hiroaki TAKAYANAGI、Yutaka UDA、Kimio FURUHATA

  DOI：10.1248/cpb.43.1844

  日期：——

  Condensation of 4-methyl-7-thiocoumarin sodium salt with methyl 5-N-acetyl-4, 7, 8, 9-tetra-O-acetyl-2-chloro-2, 3, 5-trideoxy-D-glycero-D-galacto-2-nonulopyranosonate (2), methyl 5-N-(O-acetylglycolyl)-4, 7, 8, 9-tetra-O-acetyl-2-chloro-2, 3, 6-trideoxy-D-glycero-D-galacto-2-nonulopyranosonate (11), and methyl 4, 5, 7, 8, 9-penta-O-acetyl-2-chloro-2, 3-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate (14) under Williamson reaction conditions gave the corresponding α-glycosides in good yields. Deprotection of these α-glycosides gave three new fluorogenic substrates, the 4-methylcoumarin-7-yl S-glycosides of N-acetylneuraminic acid, N-glycolylneuraminic acid, and 3-deoxy-D-glucose-D-galacto-2-nonulopyranosonic acid (KDN). Furthermore, we have developed a facile method for preparation of benzyl 5-amino-3, 5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (7), a key intermediate for the synthesis of N-glycolylneuraminic acid.

  4-甲基-7-硫代香豆素钠盐与 5-N-乙酰基-4，7，8，9-O-四乙酰基-2-氯-2，3，5-三脱氧-D-甘油-D-半乳-2-壬磺吡喃糖酸甲酯 (2)、5-N-(O-乙酰基甘氨酰)-4，7，8，9-O-四乙酰基-2-氯-2，3，6-三脱氧-D-甘油-D-半乳-2-壬磺吡喃糖酸甲酯 (11) 和 4，5，7，8，9-O-五乙酰基-2-氯-2-壬磺吡喃糖酸甲酯的缩合在威廉姆森反应条件下，5-N-(O-乙酰基甘氨酰)-4，7，8，9-四-O-乙酰基-2-氯-2，3，6-三脱氧-D-甘油-D-半乳糖-2-壬磺吡喃糖酸甲酯（11）和 4，5，7，8，9-五-O-乙酰基-2-氯-2，3-二脱氧-D-甘油-D-半乳糖-2-壬磺吡喃糖酸甲酯（14）以良好的产率得到了相应的 α-糖苷。对这些 α-糖苷进行脱保护处理，可得到三种新的含氟底物，即 N-乙酰神经氨酸、N-乙酰神经氨酸和 3-脱氧-D-葡萄糖-D-半乳糖-2-壬磺吡喃糖酸（KDN）的 4-甲基香豆素-7-基 S-糖苷。此外，我们还开发了一种简便的方法来制备 5-氨基-3,5-二脱氧-α-D-甘油-D-半乳糖-2-壬磺吡喃糖酸苄酯 (7)，这是合成 N-乙酰神经氨酸的关键中间体。
• Multivalent inhibition of the Aspergillus fumigatus KDNase
  作者：Mathieu Scalabrini、Denis Loquet、Camille Rochard、Mélyne Baudin Marie、Coralie Assailly、Yoan Brissonnet、Franck Daligault、Amélie Saumonneau、Annie Lambert、Cyrille Grandjean、David Deniaud、Paul Lottin、Sagrario Pascual、Laurent Fontaine、Viviane Balloy、Sébastien G. Gouin

  DOI：10.1039/d4ob00601a

  日期：——

  the protein. A polymeric compound with an average of 54 KDN motifs was also designed by click chemistry. Inhibitory assays performed on recombinant AfKDNAse showed a moderate and strong enzymatic inhibition for the two classes of compounds, respectively. The poly-KDN showed more than a nine hundred fold improved inhibitory activity (IC50 = 1.52 ± 0.37 μM, 17-fold in a KDN molar basis) compared to a

  烟曲霉是一种腐生真菌和机会性病原体，通常会导致免疫功能低下患者致命的感染。最近， Af KDNAse 被鉴定和表征，它是一种外切糖苷酶，可水解 3-脱氧-D-半乳糖-D-甘油-nonulosonic 酸（KDN），一种来自唾液酸家族的稀有糖。 Af KDNAse 的主要功能尚不清楚，但一项研究表明它在真菌细胞壁形态和毒力中发挥着关键作用。需要有效的Af KDNAse 抑制剂来更好地探索该酶的生物学作用并作为潜在的抗毒因子。在这项工作中，我们开发了一套基于酶稳定的硫代 KDN 基序的Af KDNAse 抑制剂。 C2、C9 连接的异源二 KDN 被设计成适合蛋白质中异常紧密的 KDN 糖结合口袋。还通过点击化学设计了平均具有 54 个 KDN 基序的聚合物。对重组Af KDNAse 进行的抑制测定显示，这两类化合物分别具有中度和强的酶抑制作用。与单价 KDN 参考相比，聚 KDN 的抑制活性提高了