Methyl 5-acetamido-4-O-benyl-2,3,5-trideoxy-8,9-O-isopropylidene-D-glycero-D-galacto-non-2-enopyranosonate | 353301-95-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Methyl 5-acetamido-4-O-benyl-2,3,5-trideoxy-8,9-O-isopropylidene-D-glycero-D-galacto-non-2-enopyranosonate
• 英文别名: methyl (2R,3R,4S)-3-acetamido-2-[(S)-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-hydroxymethyl]-4-phenylmethoxy-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 353301-95-8
• 化学式: C₂₂H₂₉NO₈
• 分子量: 435.474
• InChiKey: PHOCETGQVUGMNW-CJSSEVFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Methyl 5-acetamido-4-O-benyl-2,3,5-trideoxy-8,9-O-isopropylidene-D-glycero-D-galacto-non-2-enopyranosonate 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 3.0h， 生成 Methyl 5-acetamido-4-O-benzyl-3,5-dideoxy-8,9-O-isopropylidene-3-phenylthio-β-D-erythro-L-gluco-2-nonulopyranosonate-diethylphosphite
  参考文献：
  名称：

  Synthesis of Ganglioside GD3 and its Comparison with Bovine GD3 with Regard to Oligodendrocyte Apoptosis Mitochondrial Damage

  摘要：

  2,3-Dehydroneuraminic acid derivative 5 was transformed in five efficient steps into sialyl donor 2, which has a phenylthio group on the beta-side of the 3-position for anchimeric assistance and a diethyl phosphite residue as leaving group at the anomeric carbon. The known GM3 intermediate 10 was transformed into the 4b,4c,8c-O-unprotected acceptor 3, which was then allowed to react with 2 by using TMSOTf as catalyst and acetonitrile as solvent to afford the desired tetrasaccharide 12, which has an alpha(2-8)-linkage between two neuraminic acid residues. Removal of the phenylthio group gave intermediate 13, which was transformed into O-tetraosyl trichloroacetimidate 16 as glycosyl donor. Application of the azidosphingosine glycosylation procedure furnished GD3 (1) in high overall yield. Comparison of synthetic GD3 with bovine-brain-derived GD3 showed that there were similar effects in GD3-triggered uncoupling of mitochondrial respiration and in induction of apoptosis in oligodendrocytes.

  DOI：

  10.1002/1521-3765(20010518)7:10<2178::aid-chem2178>3.0.co;2-e
• 作为产物：
  描述：

  methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate 在 sodium methylate 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 2.0h， 生成 Methyl 5-acetamido-4-O-benyl-2,3,5-trideoxy-8,9-O-isopropylidene-D-glycero-D-galacto-non-2-enopyranosonate
  参考文献：
  名称：

  合成和评估作为人副流感病毒3型唾液酸酶活性抑制剂的4-O-烷基化的2-deoxy-2,3-didehydro-N-乙酰神经氨酸衍生物。

  摘要：

  来自新城疫病毒的副粘病毒表面糖蛋白血凝素神经氨酸酶（HN）的X射线晶体结构被用作模板来设计人类副流感病毒3型（hPIV-3）的HN抑制剂。发现从8,9-O-异亚丙基化-Neu5Ac2en1Me获得的2-脱氧-2,3-二氢-N-乙酰神经氨酸的4-O-烷基化衍生物可抑制hPIV-的唾液酸酶（神经氨酸酶）活性。 3（菌株C243）在3-30μM的范围内。与母体4-羟基化合物相比，这具有可比或更高的活性。

  DOI：

  10.1016/j.bmcl.2006.12.105

文献信息

• Synthesis and evaluation of 4-O-alkylated 2-deoxy-2,3-didehydro-N-acetylneuraminic acid derivatives as inhibitors of human parainfluenza virus type-3 sialidase activity
  作者：David J. Tindal、Jeffrey C. Dyason、Robin J. Thomson、Takashi Suzuki、Hiroo Ueyama、Yohta Kuwahara、Naoyoshi Maki、Yasuo Suzuki、Mark von Itzstein

  DOI：10.1016/j.bmcl.2006.12.105

  日期：2007.3

  haemagglutinin-neuraminidase (HN) from Newcastle Disease virus was used as a template to design inhibitors of the HN from human parainfluenza virus type-3 (hPIV-3). 4-O-Alkylated derivatives of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), accessed from 8,9-O-isopropylidenated-Neu5Ac2en1Me, were found to inhibit the sialidase (neuraminidase) activity of hPIV-3 (strain C243) in the range of 3-30muM

  来自新城疫病毒的副粘病毒表面糖蛋白血凝素神经氨酸酶（HN）的X射线晶体结构被用作模板来设计人类副流感病毒3型（hPIV-3）的HN抑制剂。发现从8,9-O-异亚丙基化-Neu5Ac2en1Me获得的2-脱氧-2,3-二氢-N-乙酰神经氨酸的4-O-烷基化衍生物可抑制hPIV-的唾液酸酶（神经氨酸酶）活性。 3（菌株C243）在3-30μM的范围内。与母体4-羟基化合物相比，这具有可比或更高的活性。
• Synthesis of Ganglioside GD3 and its Comparison with Bovine GD3 with Regard to Oligodendrocyte Apoptosis Mitochondrial Damage
  作者：Julio C. Castro-Palomino、Bernadett Simon、Oliver Speer、Marcel Leist、Richard R. Schmidt

  DOI：10.1002/1521-3765(20010518)7:10<2178::aid-chem2178>3.0.co;2-e

  日期：2001.5.18

  2,3-Dehydroneuraminic acid derivative 5 was transformed in five efficient steps into sialyl donor 2, which has a phenylthio group on the beta-side of the 3-position for anchimeric assistance and a diethyl phosphite residue as leaving group at the anomeric carbon. The known GM3 intermediate 10 was transformed into the 4b,4c,8c-O-unprotected acceptor 3, which was then allowed to react with 2 by using TMSOTf as catalyst and acetonitrile as solvent to afford the desired tetrasaccharide 12, which has an alpha(2-8)-linkage between two neuraminic acid residues. Removal of the phenylthio group gave intermediate 13, which was transformed into O-tetraosyl trichloroacetimidate 16 as glycosyl donor. Application of the azidosphingosine glycosylation procedure furnished GD3 (1) in high overall yield. Comparison of synthetic GD3 with bovine-brain-derived GD3 showed that there were similar effects in GD3-triggered uncoupling of mitochondrial respiration and in induction of apoptosis in oligodendrocytes.