甲基4,5-二-O-乙酰基-2,6-脱水-3-脱氧-6-(1,2,3-三乙酰氧基丙基)己-2-酮酸酯 | 136737-07-0

• 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
• 中文名称: 甲基4,5-二-O-乙酰基-2,6-脱水-3-脱氧-6-(1,2,3-三乙酰氧基丙基)己-2-酮酸酯
• 中文别名: (3bS,5aR,6S,7S,9aR,9bR)-7-羟基-3b,6-二(羟甲基)-6,9a-二甲基-3b,5,5a,6,7,9,9a,9b,10,11-十氢菲并[1,2-c]呋喃-8(4H)-酮；8-(2-氨基-1-甲基-D3-6-苯基咪唑并[4,5-b]吡啶基-2'-脱氧鸟苷
• 英文名称: methyl 4,5,7,8,9-penta-O-acetyl-2,3-dideoxy-D-glycero-D-galacto-2-non-2-enopyranosonate
• 英文别名: methyl 4,5,7,8,9-penta-O-acetyl-2,3,5-trideoxy-D-glycero-D-galacto-non-2-eno-pyranosonate；methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-3-deoxy-D-glycero-D-galacto-non-2-enoate；methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-3-deoxy-D-glycero-D-galactonon-2-enonate；methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-3-deoxy-D-glycero-D-galacto-2-non-2-enoate；Methyl 4,5,7,8,9-penta-O-acetyl-2,6-anhydro-3-deoxy-D-glycero-D-galacto-non-2-enonate；methyl (2R,3R,4S)-3,4-diacetyloxy-2-[(1R,2R)-1,2,3-triacetyloxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 136737-07-0
• 化学式: C₂₀H₂₆O₁₃
• 分子量: 474.419
• InChiKey: PSLDDVLWELZUJX-AIHBUXEESA-N

物化性质

• 沸点：
  503.5±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  33
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 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：

  甲基4,5-二-O-乙酰基-2,6-脱水-3-脱氧-6-(1,2,3-三乙酰氧基丙基)己-2-酮酸酯 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 反应 12.0h， 以87%的产率得到(2S,5R,6R)-5-Acetoxy-6-((1R,2R)-1,2,3-triacetoxy-propyl)-tetrahydro-pyran-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Syntheses of 2,6-Anhydro-3-Deoxy-D-Glycero-D-Galacto-Non-2-Enonic Acid (Kdn2En) and Its Hydrogenation Products¹

  摘要：

  Methyl 4,5,7,8,9-penta-O-acetyl-2, 6-anhydro-3-deoxy-D-glycero-D-galacto-non-2-enonate (5) was synthesized from KDN methyl ester 2 with a catalytic amount of concentrated sulfuric acid in acetic anhydride, or from 2-chloro-KDN methyl ester 4 with DBU in good yield. Hydrogenation of 4 and 5 with 10% Pd-C gave 2-deoxy-2-H-ax-KDN 8 and 2-deoxy-2-H-eq-KDN derivative 11 in high yield, respectively. The structures of these compounds were elucidated from the MS, elemental analysis, H-1 NMR and C-13 NMR data.

  DOI：

  10.1080/07328309708007333
• 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 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 以63%的产率得到甲基4,5-二-O-乙酰基-2,6-脱水-3-脱氧-6-(1,2,3-三乙酰氧基丙基)己-2-酮酸酯
  参考文献：
  名称：

  2,3-Didehydro-2-deoxysialic acids structurally varied at C-5 and their behaviour towards the sialidase from Vibrio cholerae

  摘要：

  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.

  DOI：

  10.1016/0008-6215(92)84150-q

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
• Stereoselective Synthesis of α-Keto-deoxy-D-glycero-D-galacto-nonulosonic Acid Glycosides by Means of the 4,5-O-Carbonate Protecting Group
  作者：David Crich、Chandrasekhar Navuluri

  DOI：10.1002/anie.200907178

  日期：——

  Unrivaled: A 1‐adamantyl thioglycoside derivative of the nonulosonic acid KDN, carrying a 4,5‐O‐carbonate protecting group, is a highly efficient and α‐selective KDN donor when activated using N‐iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH). Glycosylations conducted with this protecting group do not suffer from competing glycal formation.

  无与伦比的：非酮糖酸 KDN 的 1-金刚烷基硫糖苷衍生物，带有 4,5- O-碳酸酯保护基团，当使用N-碘代琥珀酰亚胺 (NIS) 和三氟甲磺酸 (TfOH ）。用该保护基团进行的糖基化不会受到竞争性糖基形成的影响。
• Facile anomer-oriented syntheses of 4-methylumbelliferyl sialic acid glycosides
  作者：Abdullah A. Hassan、Stefan Oscarson

  DOI：10.1039/d1ob00877c

  日期：——

  reaction of iodine and the aglycone to the corresponding glycal followed by reduction of the resulting 3-iodo compounds. Both anomer-oriented synthetic pathways allow for gram-scale stereoselective syntheses of the desired C-5 modified neuraminic acid derivatives for use as tools to quantify the enzymatic activity and substrate specificity of known sialidases, and potential detection and investigation

  作为寻找新唾液酸酶并确定其酶特异性和催化活性的计划的一部分，从N-乙酰神经氨酸制备了在 C-5 位置衍生的 4-甲基伞形酮唾液酸糖苷文库。α-和β-4-甲基伞形酮唾液酸糖苷均以高产率和立体选择性制备。α-异头物通过使用添加剂 CH 3的试剂控制获得CN 和 TBAI，而 β-异头异构体是通过碘和苷元与相应的糖醛的非对映选择性加成反应，然后还原所得的 3-碘化合物来合成的。两种面向异头异构体的合成途径都允许对所需的 C-5 修饰的神经氨酸衍生物进行克级立体选择性合成，用作量化已知唾液酸酶的酶活性和底物特异性的工具，以及对新型唾液酸酶的潜在检测和研究。
• 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％。
• THE SYNTHESIS OF SOME C-4 AND C-9 SUBSTITUTED DERIVATIVES OF KDN2EN METHYL ESTER
  作者：Adele Norton、Gaik Kok、Mark Itzstein

  DOI：10.1081/car-100108270

  日期：——

  and 10. Treatment of 3 with KSAc gave the 9-thioacetyl derivative which was isolated as the peracetate 11. 4-C-Ethenyl-4-deoxy (14), 4-C-phenyl-4-deoxy (15) and 4-C-[1-(methoxycarbonyl)ethenyl]-4-deoxy (16) derivatives of 2were prepared via the palladium-catalysed coupling of the 4-epi-chloride, methyl 5,7,8,9-tetra-O-acetyl-2,6-anhydro-4-chloro-3,4-dideoxy-D-glycero-D-talo-non-2-enonate (12) with the

  报道了KDN2en甲酯2的许多C-4和C-9取代的衍生物的合成。9-脱氧-9-碘，9-叠氮基-9-脱氧和9- ö甲基的衍生物2（化合物5，7和9由相应的9-制备）ø -tosylate，2,6-脱水- 3-脱氧-9- ø - p -toluenesulfonyl- d -甘油基- d -半乳-壬-2- enonate（3）。这些化合物已被充分表征为过乙6，8和10。用KSAc处理3得到9-硫代乙酰基衍生物，其被分离为过乙酸盐11。4- Ç -乙烯基-4-脱氧（14），4- Ç苯基4-脱氧（15）和4- Ç - [1-（甲氧基羰基）乙烯基] -4-脱氧（16）的衍生物2中制备通过钯催化的4-耦合外延-氯化物，甲基5,7,8,9-四- ø -乙酰基-2,6-脱水-4-氯-3,4-二脱氧d -甘油基- d -距骨-壬-2- enonate（12）与适当的有机锡烷。