(2R,3R,4R,5R)-N-(2,3:4,6-di(isopropylidenedioxy)hexan-1-ol-5-yl)-2-chloro-acetamide | 872037-93-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3R,4R,5R)-N-(2,3:4,6-di(isopropylidenedioxy)hexan-1-ol-5-yl)-2-chloro-acetamide
• 英文别名: 2-chloro-N-[(4R,5R)-4-[(4S,5R)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-1,3-dioxan-5-yl]acetamide
• CAS: 872037-93-9
• 化学式: C₁₄H₂₄ClNO₆
• 分子量: 337.801
• InChiKey: FITDPJQVGQHSDS-CNVPUSNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5R)-N-(2,3:4,6-di(isopropylidenedioxy)hexan-1-ol-5-yl)-2-chloro-acetamide 在 草酰氯 、 二甲基亚砜 、 三乙胺 、 氨 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 20.83h， 以79%的产率得到(3aR,3bS,6bR,10aR,10bS)-2,2,9,9-tetramethyl-1,3,8,10-tetraoxacyclohexa-[e]cyclopenta[g]-6-on-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
• 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 、 四丁基氟化铵 、 sodium acetate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 22.25h， 生成 (2R,3R,4R,5R)-N-(2,3:4,6-di(isopropylidenedioxy)hexan-1-ol-5-yl)-2-chloro-acetamide
  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.