(3aR,3bS,6bR,10aR,10bS)-2,2,9,9-tetramethyl-1,3,8,10-tetraoxacyclohexa[e]cyclopenta[g]-5,6-dione-4-(2,2-dimethyl-1,3-dioxan-5-yl)-4-azaindolizidine | 872038-14-7

• 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
• 英文名称: (3aR,3bS,6bR,10aR,10bS)-2,2,9,9-tetramethyl-1,3,8,10-tetraoxacyclohexa[e]cyclopenta[g]-5,6-dione-4-(2,2-dimethyl-1,3-dioxan-5-yl)-4-azaindolizidine
• 英文别名: (1R,6S,7R,11S,12R)-5-(2,2-dimethyl-1,3-dioxan-5-yl)-9,9,14,14-tetramethyl-8,10,13,15-tetraoxa-2,5-diazatetracyclo[10.4.0.02,6.07,11]hexadecane-3,4-dione
• CAS: 872038-14-7
• 化学式: C₂₀H₃₀N₂O₈
• 分子量: 426.467
• InChiKey: SNJDIMGQVVZVET-MRLBHPIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  96
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3aR,3bS,6bR,10aR,10bS)-2,2,9,9-tetramethyl-1,3,8,10-tetraoxacyclohexa[e]cyclopenta[g]-5,6-dione-4-(2,2-dimethyl-1,3-dioxan-5-yl)-4-azaindolizidine 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.5h， 以100%的产率得到(5R,6R,7S,8R,8aS)-6,7,8-trihydroxy-1-(2-hydroxy-1-(hydroxymethyl)ethyl)-5-(hydroxymethyl)hexahydroimidazo[1,2-a]pyridine-2,3-dione
  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 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 、 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 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.25h， 生成 (3aR,3bS,6bR,10aR,10bS)-2,2,9,9-tetramethyl-1,3,8,10-tetraoxacyclohexa[e]cyclopenta[g]-5,6-dione-4-(2,2-dimethyl-1,3-dioxan-5-yl)-4-azaindolizidine
  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