benzyl 2-acetamido-4,5,6-tri-O-acetyl-2-deoxy-α-D-mannopyranoside | 10375-65-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: benzyl 2-acetamido-4,5,6-tri-O-acetyl-2-deoxy-α-D-mannopyranoside
• 英文别名: phenylmethyl 3,4,6-tri-O-acetyl-2-acetylamino-2-deoxy-α-D-mannopyranoside；benzyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-mannopyranoside；2-acetamido-1-O-benzyl-3,4,5-tri-O-acetyl-2-deoxy-D-mannopyranose；Benzyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-mannopyranosid；Benzyl N,3,4,6-tetra-O-acetyl-alpha-d-mannosaminide；[(2R,3S,4R,5S,6S)-5-acetamido-3,4-diacetyloxy-6-phenylmethoxyoxan-2-yl]methyl acetate
• CAS: 10375-65-2
• 化学式: C₂₁H₂₇NO₉
• 分子量: 437.447
• InChiKey: IDEBBPWXWFHKBU-XNTOXWQXSA-N

物化性质

• 熔点：
  63 °C(Solv: ethyl ether (60-29-7); hexane (110-54-3))
• 沸点：
  587.0±50.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  benzyl 2-acetamido-4,5,6-tri-O-acetyl-2-deoxy-α-D-mannopyranoside 在 palladium on activated charcoal 2,6-二甲基吡啶 、 DL-dithiothreitol 、 氢气 、 sodium methylate 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 116.5h， 生成 9-O-(dimethylphosphinyl)-N-acetylneuraminic acid
  参考文献：
  名称：

  Overproduction of CMP-sialic acid synthetase for organic synthesis

  摘要：

  The gene coding for Escherichia coli CMP-sialic acid synthetase (E.C. 2.7.7.43) was cloned and overexpressed in E. coli through a primer-directed polymerase chain reaction. Two plasmids were constructed to produce the native enzyme and a modified enzyme fused with a decapeptide at the C-terminus. The decapeptide tag was used for detection of the enzyme production. Both enzymes produced from E. coli were isolated and purified with an Orange A dye resin and FPLC. Their properties were compared with respect to their kinetic parameters, stability, pH profiles, and substrate specificities. Both enzymes have similar k(cat) and K(m) for NeuAc and CTP but different pH profiles. Contrary to the native enzyme, the modified enzyme is more active at higher pH. Studies on specificity indicate that both enzymes have a high specific activity for C-9 modified NeuAc derivatives at neutral pH. Some C-5 modified (hydroxy, deoxy, and deoxyfluoro) NeuAc derivatives are not acceptable as substrates. The modified enzyme has been used in the synthesis of CMP-NeuAc from ManNAc and CMP and sialyl N-acetyllactosamine (Neu-alpha-2,6Gal-beta-1,4GlcNAc) with in situ generation of NeuAc and regeneration of CMP-NeuAc. The 6-O-acyl derivatives of ManNAc were prepared via transesterification in anhydrous dimethylformamide by using an engineered stable subtilisin variant as a catalyst, and the products were used as substrates in sialic acid aldolase-catalyzed synthesis of 9-O-acyl-NeuAc derivatives.

  DOI：

  10.1021/ja00036a044
• 作为产物：
  描述：

  N-acetyl-D-mannosamine 在 吡啶 、 三氟化硼乙醚 作用下， 以 硝基甲烷 为溶剂， 反应 12.5h， 生成 benzyl 2-acetamido-4,5,6-tri-O-acetyl-2-deoxy-α-D-mannopyranoside
  参考文献：
  名称：

  Overproduction of CMP-sialic acid synthetase for organic synthesis

  摘要：

  The gene coding for Escherichia coli CMP-sialic acid synthetase (E.C. 2.7.7.43) was cloned and overexpressed in E. coli through a primer-directed polymerase chain reaction. Two plasmids were constructed to produce the native enzyme and a modified enzyme fused with a decapeptide at the C-terminus. The decapeptide tag was used for detection of the enzyme production. Both enzymes produced from E. coli were isolated and purified with an Orange A dye resin and FPLC. Their properties were compared with respect to their kinetic parameters, stability, pH profiles, and substrate specificities. Both enzymes have similar k(cat) and K(m) for NeuAc and CTP but different pH profiles. Contrary to the native enzyme, the modified enzyme is more active at higher pH. Studies on specificity indicate that both enzymes have a high specific activity for C-9 modified NeuAc derivatives at neutral pH. Some C-5 modified (hydroxy, deoxy, and deoxyfluoro) NeuAc derivatives are not acceptable as substrates. The modified enzyme has been used in the synthesis of CMP-NeuAc from ManNAc and CMP and sialyl N-acetyllactosamine (Neu-alpha-2,6Gal-beta-1,4GlcNAc) with in situ generation of NeuAc and regeneration of CMP-NeuAc. The 6-O-acyl derivatives of ManNAc were prepared via transesterification in anhydrous dimethylformamide by using an engineered stable subtilisin variant as a catalyst, and the products were used as substrates in sialic acid aldolase-catalyzed synthesis of 9-O-acyl-NeuAc derivatives.

  DOI：

  10.1021/ja00036a044

文献信息

• [EN] MONOSACCHARIDE PHOSPHORAMIDATE PRODRUGS<br/>[FR] PROMÉDICAMENTS À BASE DE PHOSPHORAMIDATE DE MONOSACCHARIDE
  申请人：CERECOR INC

  公开号：WO2019118486A1

  公开（公告）日：2019-06-20

  The present disclosure provides monosaccharide phosphoramidate prodrugs of monosaccharide monophosphates. The present disclosure further provides methods of treating diseases of conditions such as congenital disorders of glycosylation comprising administering the monosaccharide phosphoramidate prodrugs of the present disclosure to a patient in need thereof.

  本公开提供了单糖磷酰胺酯前药，用于单糖单磷酸。本公开还提供了治疗糖基化先天性疾病等疾病或症状的方法，包括向需要的患者施用本公开的单糖磷酰胺酯前药。
• A new synthesis of 1,2-trans-2-acetamido-2-deoxyglycopyranosides via 1,2-trans-2-deoxy-2-iodoglycosyl azides
  作者：Dominique Lafont、Pascal Guilloux、Gérard Descotes

  DOI：10.1016/0008-6215(89)85107-9

  日期：1989.10

  Abstract Trans -addition of iodoazide to the double bond of 3,4,6-tri- O -acetyl-1,5-anhydro- d - arabino -hex-1-enitol yielded 2-deoxy-2-iodoglycosyl azides, which are precursors of 1,2- trans -2-amino-2-deoxyglycopyranosides when treated by an alcohol in the presence of triphenylphosphine.

  摘要碘叠氮化物在3,4,6-tri-O-乙酰基1,5,5-脱水-d-阿拉伯糖基-己糖-1-烯醇的双键上的反式加成反应生成了2-deoxy-2-iodoglycosyl azides。在三苯基膦存在下用醇处理的1,2-反式-2-氨基-2-氨基-2-脱氧糖吡喃糖苷的前体。
• Preparation of a fluorous protecting group and its application to the chemoenzymatic synthesis of sialidase inhibitor
  作者：Kiyoshi Ikeda、Hitomi Mori、Masayuki Sato

  DOI：10.1039/b605519b

  日期：——

  ethyl chloride was prepared as a novel fluorous protecting reagent. Neu5Ac aldolase-catalyzed chemoenzymatic transformation of N-acetyl-D-mannosamine to Neu5Ac derivatives was achieved successfully by using the fluorous reagent not only for hydroxy group protection but also for fluorous tagging. This chemoenzymatic method was applied to the synthesis of 2-deoxy-2,3-didehydrosialic acid 1 known as a

  制备了2-（全氟己基）乙氧基甲基氯作为新型氟保护剂。通过使用氟试剂不仅用于羟基保护而且还用于氟标记，成功地实现了Neu5Ac醛缩酶催化的N-乙酰基-D-甘露糖胺化学转化为Neu5Ac衍生物。该化学酶法被用于合成被称为有效唾液酸酶抑制剂的2-脱氧-2，3-二氢氢化唾液酸1。
• Targeting GNE Myopathy: A Dual Prodrug Approach for the Delivery of <i>N</i>-Acetylmannosamine 6-Phosphate
  作者：Chiara Morozzi、Jana Sedláková、Michaela Serpi、Marialuce Avigliano、Rosangela Carbajo、Lucia Sandoval、Yadira Valles-Ayoub、Patrick Crutcher、Stephen Thomas、Fabrizio Pertusati

  DOI：10.1021/acs.jmedchem.9b00833

  日期：2019.9.12

  ProTides comprise an important class of prodrugs currently marketed and developed as antiviral and anticancer therapies. The ProTide technology employs phosphate masking groups capable of providing more favorable druglike properties and an intracellular activation mechanism for enzyme-mediated release of a nucleoside monophosphate. Herein, we describe the application of phosphoramidate chemistry to 1,3,4-O-acetylated N-acetylmannosamine (Ac(3)ManNAc) to deliver ManNAc-6-phosphate (ManNAc-6-P), a critical intermediate in sialic acid biosynthesis. Sialic acid deficiency is a hallmark of GNE myopathy, a rare congenital disorder of glycosylation (CDG) caused by mutations in GNE that limit the production of ManNAc-6-P. Synthetic methods were developed to provide a library of Ac(3)ManNAc-6-phosphoramidates that were evaluated in a series of studies for their potential as a treatment for GNE myopathy. Prodrug 12b showed rapid activation in a carboxylesterase (CPY) enzymatic assay and favorable ADME properties, while also being more effective than ManNAc at increasing sialic acid levels in GNE-deficient cell lines. These results provide a potential platform to address substrate deficiencies in GNE myopathy and other CDGs.
• Enzymatic synthesis of 7-deoxy-N-acetylneuraminic acid and 7-O-methyl-N-acetylneuraminic acid
  作者：Randall L. Halcomb、Wolfgang Fitz、Chi-Huey Wong

  DOI：10.1016/s0957-4166(00)80390-0

  日期：1994.12

  7-Deoxy-N-acetylneuraminic Acid and 7-O-methyl-N-acetylneuraminic acid were synthesized through the sialic acid aldolase-cataIyzed aldol addition reactions of 4-deoxy-N-acetyl-D-mannosamine and 4-O-methyl-N-acetyl-D-mannosamine, respectively, with pyruvate. The obtained sialic acids will be used as probes for the investigation of the unusual mechanism of a novel sialidase from leech.