methyl 3-[(2R,3S)-3-[(1S,2R,3R)-3-azido-1,2,4-tris(phenylmethoxy)butyl]oxiran-2-yl]propanoate | 180196-32-1

• 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 3-[(2R,3S)-3-[(1S,2R,3R)-3-azido-1,2,4-tris(phenylmethoxy)butyl]oxiran-2-yl]propanoate
• CAS: 180196-32-1
• 化学式: C₃₁H₃₅N₃O₆
• 分子量: 545.635
• InChiKey: HQLGMFLMAGCUMS-KVDYRNGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  40
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  80.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 3-[(2R,3S)-3-[(1S,2R,3R)-3-azido-1,2,4-tris(phenylmethoxy)butyl]oxiran-2-yl]propanoate 在 palladium dihydroxide 氢气 、 sodium methylate 作用下， 生成 (1R,2R,3R,8R,8aR)-8-hydroxy-1,2-bis(phenylmethoxy)-3-(phenylmethoxymethyl)-2,3,6,7,8,8a-hexahydro-1H-indolizin-5-one
  参考文献：
  名称：

  Synthesis of Novel Glycosidase-Inhibitory Hydroxymethyl-Substituted Polyhydroxylated Indolizidines:  Ring-Expanded Analogs of the Pyrrolizidine Alkaloids Alexine and Australine

  摘要：

  The pyrrolizidine azasugars alexine (3) and australine (4) and their stereoisomers are glycosidase inhibitors of potential therapeutic use. Since the glycosidase inhibitory activity of azasugars is profoundly effected by ring size modification, the ring-expanded indolizidine analogs 7 (homoalexine), 8 (8-epihomoaustraline), 9 (homoaustraline), and 10 (8-epihomoalexine) were prepared. L-Xylose was converted into the diols 16, which were transformed into the nine-membered lactones 18 by Claisen rearrangment of the cyclic ketene acetal 17. Transesterification of the lactones to the hydroxy esters 19 followed by azide displacement and epoxidation gave the epoxides 21 and 31, Reductive double cyclization of these azido-epoxides followed by functional group adjustment provided the desired homologs 7-10. An alternative route involving stereoselective epoxidation of the nine-membered lactones was also examined. The homologs 7-10 were found to be good inhibitors of amyloglucosidase (Aspergillus niger). The inhibitory activities of 8 and 10 are comparable to those exhibited by castanospermine (5) and the pyrrolizidines alexine (3), australine (4), and 7-epiaustraline, Indolizidines 7-10 do not inhibit beta-glucosidase (almond) or alpha-glucosidase (bakers' yeast). This activity parallels that exhibited by the pyrrolizidine inhibitors alexine, australine, and 7-epiaustraline, which are generally good amyloglucosidase inhibitors but relatively weak inhibitors of alpha-glucosidase and beta-glucosidase. However, in contrast to the pyrrolizidine inhibitors which have not been reported to possess mannosidase inhibitory activity, the indolizidines 7-10 were found to inhibit alpha-mannosidase (jack bean), albeit weakly.

  DOI：

  10.1021/jo960610a
• 作为产物：
  描述：

  (1R,6S,7R,8S,9S)-7,8-bis(phenylmethoxy)-6-(phenylmethoxymethyl)-5,10-dioxabicyclo[7.1.0]decan-4-one 在 迭氮酸 、 碳酸氢钠 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 4.5h， 生成 methyl 3-[(2R,3S)-3-[(1S,2R,3R)-3-azido-1,2,4-tris(phenylmethoxy)butyl]oxiran-2-yl]propanoate
  参考文献：
  名称：

  Synthesis of Novel Glycosidase-Inhibitory Hydroxymethyl-Substituted Polyhydroxylated Indolizidines:  Ring-Expanded Analogs of the Pyrrolizidine Alkaloids Alexine and Australine

  摘要：

  The pyrrolizidine azasugars alexine (3) and australine (4) and their stereoisomers are glycosidase inhibitors of potential therapeutic use. Since the glycosidase inhibitory activity of azasugars is profoundly effected by ring size modification, the ring-expanded indolizidine analogs 7 (homoalexine), 8 (8-epihomoaustraline), 9 (homoaustraline), and 10 (8-epihomoalexine) were prepared. L-Xylose was converted into the diols 16, which were transformed into the nine-membered lactones 18 by Claisen rearrangment of the cyclic ketene acetal 17. Transesterification of the lactones to the hydroxy esters 19 followed by azide displacement and epoxidation gave the epoxides 21 and 31, Reductive double cyclization of these azido-epoxides followed by functional group adjustment provided the desired homologs 7-10. An alternative route involving stereoselective epoxidation of the nine-membered lactones was also examined. The homologs 7-10 were found to be good inhibitors of amyloglucosidase (Aspergillus niger). The inhibitory activities of 8 and 10 are comparable to those exhibited by castanospermine (5) and the pyrrolizidines alexine (3), australine (4), and 7-epiaustraline, Indolizidines 7-10 do not inhibit beta-glucosidase (almond) or alpha-glucosidase (bakers' yeast). This activity parallels that exhibited by the pyrrolizidine inhibitors alexine, australine, and 7-epiaustraline, which are generally good amyloglucosidase inhibitors but relatively weak inhibitors of alpha-glucosidase and beta-glucosidase. However, in contrast to the pyrrolizidine inhibitors which have not been reported to possess mannosidase inhibitory activity, the indolizidines 7-10 were found to inhibit alpha-mannosidase (jack bean), albeit weakly.

  DOI：

  10.1021/jo960610a

文献信息

• Synthesis of Novel Glycosidase-Inhibitory Hydroxymethyl-Substituted Polyhydroxylated Indolizidines:  Ring-Expanded Analogs of the Pyrrolizidine Alkaloids Alexine and Australine
  作者：William H. Pearson、Erik J. Hembre

  DOI：10.1021/jo960610a

  日期：1996.1.1

  The pyrrolizidine azasugars alexine (3) and australine (4) and their stereoisomers are glycosidase inhibitors of potential therapeutic use. Since the glycosidase inhibitory activity of azasugars is profoundly effected by ring size modification, the ring-expanded indolizidine analogs 7 (homoalexine), 8 (8-epihomoaustraline), 9 (homoaustraline), and 10 (8-epihomoalexine) were prepared. L-Xylose was converted into the diols 16, which were transformed into the nine-membered lactones 18 by Claisen rearrangment of the cyclic ketene acetal 17. Transesterification of the lactones to the hydroxy esters 19 followed by azide displacement and epoxidation gave the epoxides 21 and 31, Reductive double cyclization of these azido-epoxides followed by functional group adjustment provided the desired homologs 7-10. An alternative route involving stereoselective epoxidation of the nine-membered lactones was also examined. The homologs 7-10 were found to be good inhibitors of amyloglucosidase (Aspergillus niger). The inhibitory activities of 8 and 10 are comparable to those exhibited by castanospermine (5) and the pyrrolizidines alexine (3), australine (4), and 7-epiaustraline, Indolizidines 7-10 do not inhibit beta-glucosidase (almond) or alpha-glucosidase (bakers' yeast). This activity parallels that exhibited by the pyrrolizidine inhibitors alexine, australine, and 7-epiaustraline, which are generally good amyloglucosidase inhibitors but relatively weak inhibitors of alpha-glucosidase and beta-glucosidase. However, in contrast to the pyrrolizidine inhibitors which have not been reported to possess mannosidase inhibitory activity, the indolizidines 7-10 were found to inhibit alpha-mannosidase (jack bean), albeit weakly.