2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-mannopyranose | 10294-12-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-mannopyranose
• 英文别名: [(2R,3S,4R,5S)-5-acetamido-3,4-diacetyloxy-6-hydroxyoxan-2-yl]methyl acetate
• CAS: 10294-12-9
• 化学式: C₁₄H₂₁NO₉
• 分子量: 347.322
• InChiKey: HUQNDNAQVPCTFV-DYPLGBCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-mannopyranose 在 chromium(VI) oxide 、 溶剂黄146 作用下， 以44%的产率得到2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-manno-1,5-lactone
  参考文献：
  名称：

  Versatile intermediates in the selective modification of the amino function of 2-amino-2-deoxy-d-mannopyranose and the 3-position of 2-acetamido-2-deoxy-d-mannose: Potential membrane modifiers in neoplastic control

  摘要：

  A general method has been developed to selectively modify the amino group of 2-amino-2-deoxy-D-mannopyranose (D-mannosamine), a precursor of the terminal membrane sugar, sialic acid. 1,3,4,6-Tetra-O-acetyl-2-amino-2-deoxy-alpha-D-mannopyranose oxalate was prepared via two routes that allowed introduction of various acyl groups onto the amino function. These compounds were evaluated for their antineoplastic properties. The most significant preclinical therapeutic finding was the antileukemic activity found in mice for tetra-O-acetyl-2-epi-streptozotocin (the acetylated alpha-mannosamine epimer of streptozotocin). Administration of 50 mg/kg/day X 5 to leukemia L1210-bearing DBA/2Ha mice resulted in 5/5 35-day survivors. Neutralization of 1,3,3,6-tetra-O-acetyl-2-amino-2-deoxy-alpha-D-mannopyranose oxalate under aqueous conditions led to 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-alpha-D-mannopyranose, the oxidation of which gave 2-acetamido-4,6-di-O-acetyl-1,5-anhydro-2-deoxy-D-erythro-hex-1-en-3-ulose. This agent demonstrated an IC50 of 25 mu M with a murine L1210 cell culture. Administration of 100 mg/kg/day X 5 resulted in 42% ILS in DBA/2 mice with ip L1210 leukemia. Several other nonacetylated derivatives were also prepared by direct N-acylation, producing, for example, fluorescently tagged N-dansylmannosamine.

  DOI：

  10.1016/0008-6215(95)00154-l
• 作为产物：
  描述：

  2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-D-mannopyranose 以 甲醇 为溶剂， 反应 3.0h， 以60%的产率得到2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-mannopyranose
  参考文献：
  名称：

  体内中枢神经系统代谢多糖工程的碳水化合物-神经活性混合策略

  摘要：

  唾液酸在中枢神经系统 (CNS) 中含量丰富，对大脑发育、学习和记忆至关重要。已知唾液酸-糖复合物生物合成的失调与神经系统疾病、中枢神经系统损伤和脑癌有关。代谢聚糖工程 (MGE) 和生物正交连接使研究聚糖在体内的生物学作用成为可能；然而，对大脑中唾液酸聚糖的直接研究一直是棘手的。我们报告了一种利用碳水化合物-神经活性杂化 (CNH) 分子的简单策略，该策略利用血脑屏障中可用的载体介导的运输系统，通过小鼠尾静脉注射进入大脑。与神经活性载体（即烟酸、丙戊酸、茶碱-7-乙酸和胆碱）结合的全乙酰化 N-叠氮基乙酰基-d-甘露糖胺 (Ac4ManNAz)，在 SH-SY5Y（人神经母细胞瘤）细胞中合成并评估 MGE。在小鼠（C57BL/6J 和 BALB/cByJ）中静脉注射 CNH 分子导致大脑和心脏中携带 N-叠氮基乙酰神经氨酸 (NeuAz) 的糖蛋白的强烈表达，而非杂交分子 Ac4ManNAz

  DOI：

  10.1021/jacs.6b08894

文献信息

• [EN] HYBRID SCFA-HYDROXYL-DERIVATIZED MONOSACCHARIDES, METHODS OF SYNTHESIS, AND METHODS OF TREATING DISORDERS<br/>[FR] MONOSACCHARIDES HYBRIDES DÉRIVATISÉS AVEC HYDROXYLE /SCFA (ACIDES GRAS À CHAÎNE COURTE), PROCÉDÉS DE SYNTHÈSE, ET PROCÉDÉS DE TRAITEMENT DE TROUBLES
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2009020641A1

  公开（公告）日：2009-02-12

  Described herein are fatty acid carbohydrate-hydroxyl-hybrid compounds and derivatives thereof, and methods of treating or preventing disease and disease symptoms using the compounds and compositions thereof.

  本文描述了脂肪酸碳水化合物及其衍生物，以及利用这些化合物及其组合物治疗或预防疾病和疾病症状的方法。
• Synthesis of NAM-thiazoline derivatives as novel O-GlcNAcase inhibitors
  作者：Hanchu Kong、Wei Chen、Tian Liu、Huizhe Lu、Qing Yang、Yanhong Dong、Xiaomei Liang、Shuhui Jin、Jianjun Zhang

  DOI：10.1016/j.carres.2016.04.008

  日期：2016.6

  but play different physiological roles in vivo. Selective inhibition toward one of these enzymes is therefore of importance to regulate the corresponding bioprocess. Here ten new NAM-thiazoline derivatives were synthesized and subsequently characterized by NMR and HRMS. A preliminary bioassay showed that most of the synthesized compounds exhibited obvious selective inhibition against human O-GlcNAcase

  来自智人的人O-GlcNAcase（GH 84）和人β-N-乙酰基-D-己糖胺酶（GH 20）是两个治疗性酶标靶，它们具有相同的催化机制，但在体内起着不同的生理作用。因此，对这些酶之一的选择性抑制对于调节相应的生物过程很重要。在此合成了十种新的NAM-噻唑啉衍生物，随后通过NMR和HRMS进行了表征。初步的生物测定表明，大多数合成的化合物对人O-GlcNAcase的抑制作用均强于人β-N-乙酰基-D-己糖胺酶。在所测试的化合物中，化合物7d（IC50 = 6.4 µM，hOGA； IC50> 1 mM，hHex）和7f（IC50 = 11.9 µM，hOex； IC50> 1 mM，hHex）被证明是高度选择性和有效的抑制剂。
• Hexosamine Template. A Platform for Modulating Gene Expression and for Sugar-Based Drug Discovery
  作者：Noha Elmouelhi、Udayanath Aich、Venkata D. P. Paruchuri、M. Adam Meledeo、Christopher T. Campbell、Jean J. Wang、Raja Srinivas、Hargun S. Khanna、Kevin J. Yarema

  DOI：10.1021/jm801661m

  日期：2009.4.23

  This study investigates the breadth of cellular responses engendered by short chain fatty acid (SCFA)-hexosamine hybrid molecules, a class of compounds long used in "metabolic glycoengineering" that are now emerging as drug candidates. First, a "mix and match" strategy showed that different SCFA (n-butyrate and acetate) appended to the same core sugar altered biological activity, complementing previous results [Campbell et al. J. Med. Chem. 2008, 51, 8135-8147] where a single type of SCFA elicited distinct responses. Microarray profiling then compared transcriptional responses engendered by regioisomerically modified ManNAc, GlcNAc, and GalNAc analogues in MDA-MB-231 cells. These data, which were validated by qRT-PCR or Western analysis for IDI, TP53, HPSE, NQO1, EGR1, and VEGFA, showed a two-pronged response where a core set of genes was coordinately regulated by all analogues while each analogue simultaneously uniquely regulated a larger number of genes. Finally, AutoDock modeling supported a mechanism where the analogues directly interact with elements of the NF-kappa B pathway. Together, these results establish the SCFA-hexosamine template as a versatile platform for modulating biological activity and developing new therapeutics.
• New method for the 1-deacetylation of peracetates of aminosugars
  作者：S. S. Pertel'、V. Ya. Chirva

  DOI：10.1007/bf00629996

  日期：1994.3
• 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.