4-[(5R,6R,7S,8R,8aS)-6,7,8-trihydroxy-5-(hydroxymethyl)-2,3-dioxo-6,7,8,8a-tetrahydro-5H-imidazo[1,2-a]pyridin-1-yl]-N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]butanamide | 872037-86-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[(5R,6R,7S,8R,8aS)-6,7,8-trihydroxy-5-(hydroxymethyl)-2,3-dioxo-6,7,8,8a-tetrahydro-5H-imidazo[1,2-a]pyridin-1-yl]-N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]butanamide
• CAS: 872037-86-0
• 化学式: C₁₉H₃₁N₃O₁₂
• 分子量: 493.468
• InChiKey: GIZOJGFTECJVON-LMBHXZJBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  230
• 氢给体数：
  8
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4-[(5R,6R,7S,8R,8aS)-6,7,8-trihydroxy-5-(hydroxymethyl)-2,3-dioxo-6,7,8,8a-tetrahydro-5H-imidazo[1,2-a]pyridin-1-yl]-N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]butanamide 、 乙酸酐 在 吡啶 作用下， 反应 16.0h， 以12 mg的产率得到Acetic acid (5R,6R,7S,8R,8aS)-6,7-diacetoxy-5-acetoxymethyl-1-[3-((2S,3S,4R,5S,6R)-4,5-diacetoxy-6-acetoxymethyl-2-methoxy-tetrahydro-pyran-3-ylcarbamoyl)-propyl]-2,3-dioxo-octahydro-imidazo[1,2-a]pyridin-8-yl ester
  参考文献：
  名称：

  A Practical Synthesis of Kifunensine Analogues as Inhibitors of Endoplasmic Reticulum α-Mannosidase I

  摘要：

  A practical synthesis of the potent class I a-mannosidase inhibitor kifunensine (1) beginning from the inexpensive and readily available starting material L-ascorbic acid (15) is described. The protected amino-alcohol ((2R,3R,4R,5R)-5-amino-2,3:4,6-diisopropylidenedioxyhexanol, 11) served,as a key intermediate from which several N-1 substituted kifunensine analogues (including N-methyl, N-cyclohexyl, and N-bis(hydroxymethyl)methyl) and 2-desoxakifunensine analogues (including N-H and N-methyl) were prepared and screened for inhibition of human endoplasmic reticulum a-mannosidase I (ER Man 1) and mouse Golgi a-mannosidase IA (Golgi Man IA), In addition, several pseudodisaccharide kifunensine analogues in which a mannose residue was tethered to N-1 of kifunensine via a two-, three-, or four-carbon linker and an affinity-bound kifunensine analogue were also prepared and evaluated for biological activity. While the synthesized N-1 kifunesine analogues were found to be less potent inhibitors of Class I alpha-mannosidases than kifuensine itself, the bis(hydroxymethyl)methylkifunensine analogue 6 was shown to selectively inhibit ER Man I over Golgi Man IA.

  DOI：

  10.1021/jo0516382
• 作为产物：
  描述：

  (2R,3R,4R,5R)-5-azido-6-tert-butyldimethylsilanyloxy-2,3-isopropylidenedioxy-1,4-hexanediol 在 palladium dihydroxide 吡啶 、 lithium aluminium tetrahydride 、 4 A molecular sieve 、 四丁基氟化铵 、 戴斯-马丁氧化剂 、 对甲苯磺酸 、 乙二醇 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 环己烯 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.25h， 生成 4-[(5R,6R,7S,8R,8aS)-6,7,8-trihydroxy-5-(hydroxymethyl)-2,3-dioxo-6,7,8,8a-tetrahydro-5H-imidazo[1,2-a]pyridin-1-yl]-N-[(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-methoxyoxan-3-yl]butanamide
  参考文献：
  名称：

  A Practical Synthesis of Kifunensine Analogues as Inhibitors of Endoplasmic Reticulum α-Mannosidase I

  摘要：

  A practical synthesis of the potent class I a-mannosidase inhibitor kifunensine (1) beginning from the inexpensive and readily available starting material L-ascorbic acid (15) is described. The protected amino-alcohol ((2R,3R,4R,5R)-5-amino-2,3:4,6-diisopropylidenedioxyhexanol, 11) served,as a key intermediate from which several N-1 substituted kifunensine analogues (including N-methyl, N-cyclohexyl, and N-bis(hydroxymethyl)methyl) and 2-desoxakifunensine analogues (including N-H and N-methyl) were prepared and screened for inhibition of human endoplasmic reticulum a-mannosidase I (ER Man 1) and mouse Golgi a-mannosidase IA (Golgi Man IA), In addition, several pseudodisaccharide kifunensine analogues in which a mannose residue was tethered to N-1 of kifunensine via a two-, three-, or four-carbon linker and an affinity-bound kifunensine analogue were also prepared and evaluated for biological activity. While the synthesized N-1 kifunesine analogues were found to be less potent inhibitors of Class I alpha-mannosidases than kifuensine itself, the bis(hydroxymethyl)methylkifunensine analogue 6 was shown to selectively inhibit ER Man I over Golgi Man IA.

  DOI：

  10.1021/jo0516382

文献信息

• A Practical Synthesis of Kifunensine Analogues as Inhibitors of Endoplasmic Reticulum α-Mannosidase I
  作者：Kirk W. Hering、Khanita Karaveg、Kelley W. Moremen、William H. Pearson

  DOI：10.1021/jo0516382

  日期：2005.11.1

  A practical synthesis of the potent class I a-mannosidase inhibitor kifunensine (1) beginning from the inexpensive and readily available starting material L-ascorbic acid (15) is described. The protected amino-alcohol ((2R,3R,4R,5R)-5-amino-2,3:4,6-diisopropylidenedioxyhexanol, 11) served,as a key intermediate from which several N-1 substituted kifunensine analogues (including N-methyl, N-cyclohexyl, and N-bis(hydroxymethyl)methyl) and 2-desoxakifunensine analogues (including N-H and N-methyl) were prepared and screened for inhibition of human endoplasmic reticulum a-mannosidase I (ER Man 1) and mouse Golgi a-mannosidase IA (Golgi Man IA), In addition, several pseudodisaccharide kifunensine analogues in which a mannose residue was tethered to N-1 of kifunensine via a two-, three-, or four-carbon linker and an affinity-bound kifunensine analogue were also prepared and evaluated for biological activity. While the synthesized N-1 kifunesine analogues were found to be less potent inhibitors of Class I alpha-mannosidases than kifuensine itself, the bis(hydroxymethyl)methylkifunensine analogue 6 was shown to selectively inhibit ER Man I over Golgi Man IA.