(2R,3S)-2-((1S,2R,3R)-4-Azido-1,2,3-tris-benzyloxy-butyl)-3-(3-chloro-propyl)-oxirane | 180467-28-1

• 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: (2R,3S)-2-((1S,2R,3R)-4-Azido-1,2,3-tris-benzyloxy-butyl)-3-(3-chloro-propyl)-oxirane
• 英文别名: (2R,3S)-2-[(1S,2R,3R)-4-azido-1,2,3-tris(phenylmethoxy)butyl]-3-(3-chloropropyl)oxirane
• CAS: 180467-28-1
• 化学式: C₃₀H₃₄ClN₃O₄
• 分子量: 536.071
• InChiKey: ZZBBZVGXJFEHEP-OEWGIKMGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  38
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  54.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,3S)-2-((1S,2R,3R)-4-Azido-1,2,3-tris-benzyloxy-butyl)-3-(3-chloro-propyl)-oxirane 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 生成 (1S,7R,8R,9R,9aS)-7,8,9-Tris-benzyloxy-octahydro-quinolizin-1-ol
  参考文献：
  名称：

  Synthesis of Tetrahydroxyquinolizidines:  Ring-Expanded Analogs of the Mannosidase Inhibitor Swainsonine

  摘要：

  The indolizidine azasugar swainsonine (1) is an important inhibitor of mannosidase II and has shown antitumor and immunomodulatory activity. A comparison of the structure of swainsonine and D-mannopyranose shows that swainsonine lacks the C(4) hydroxymethine group of mannose. Ring-expanded quinolizidine analogs 4 of swainsonine were prepared where the ''missing'' hydroxymethine group was incorporated into the pyrrolidine ring of swainsonine between C(1) and C(8a). The quinolizidine analogs 4 resemble both D-mannopyranose and the related azasugar deoxymannojirimycin, a selective inhibitor of the glycoprotein processing enzyme mannosidase I. D-Arabinose was converted into the omega-halo azidoalkene 13, which was subjected to thermolysis, a strategy which had been successful in an earlier synthesis of swainsonine itself. Rather than the desired quinolizidine 4, the pyridinium ion 16 was produced. An alternate synthesis of all four C(9)/C(9a) diastereomers of 4 was developed which relied on the reductive double-alkylation of epoxides bearing remote azido and chloro groups. Thus, reduction of compounds 21 alpha, 21 beta, 26, and 27 resulted in the formation of the quinolizidines 22, 23, 28, and 29, which were deprotected to give the quinolizidine analogs of swainsonine (9S,9aR)-4, (9R,9aS)-4, (9S,9aS)-4, and (9R,9aR)-4, respectively. An alternate synthesis of(9R,9aR)-4 involving the reductive N-alkylation of a cyclic imine was also developed. None of the quinolizidines showed significant glycosidase activity in screens against mannosidases, glucosidases, or fucosidases. Speculation on the significance of these findings is presented.

  DOI：

  10.1021/jo960609b
• 作为产物：
  描述：

  2,3,4-tri-O-benzyl-D-arabinopyranose 在 四氧化锇 、 迭氮酸 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 sodium hydrogensulfite 、 甲基磺酰氯 、 N-甲基吗啉氧化物 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 苯 为溶剂， 反应 92.42h， 生成 (2R,3S)-2-((1S,2R,3R)-4-Azido-1,2,3-tris-benzyloxy-butyl)-3-(3-chloro-propyl)-oxirane
  参考文献：
  名称：

  Synthesis of Tetrahydroxyquinolizidines:  Ring-Expanded Analogs of the Mannosidase Inhibitor Swainsonine

  摘要：

  The indolizidine azasugar swainsonine (1) is an important inhibitor of mannosidase II and has shown antitumor and immunomodulatory activity. A comparison of the structure of swainsonine and D-mannopyranose shows that swainsonine lacks the C(4) hydroxymethine group of mannose. Ring-expanded quinolizidine analogs 4 of swainsonine were prepared where the ''missing'' hydroxymethine group was incorporated into the pyrrolidine ring of swainsonine between C(1) and C(8a). The quinolizidine analogs 4 resemble both D-mannopyranose and the related azasugar deoxymannojirimycin, a selective inhibitor of the glycoprotein processing enzyme mannosidase I. D-Arabinose was converted into the omega-halo azidoalkene 13, which was subjected to thermolysis, a strategy which had been successful in an earlier synthesis of swainsonine itself. Rather than the desired quinolizidine 4, the pyridinium ion 16 was produced. An alternate synthesis of all four C(9)/C(9a) diastereomers of 4 was developed which relied on the reductive double-alkylation of epoxides bearing remote azido and chloro groups. Thus, reduction of compounds 21 alpha, 21 beta, 26, and 27 resulted in the formation of the quinolizidines 22, 23, 28, and 29, which were deprotected to give the quinolizidine analogs of swainsonine (9S,9aR)-4, (9R,9aS)-4, (9S,9aS)-4, and (9R,9aR)-4, respectively. An alternate synthesis of(9R,9aR)-4 involving the reductive N-alkylation of a cyclic imine was also developed. None of the quinolizidines showed significant glycosidase activity in screens against mannosidases, glucosidases, or fucosidases. Speculation on the significance of these findings is presented.

  DOI：

  10.1021/jo960609b

文献信息

• Synthesis of Tetrahydroxyquinolizidines:  Ring-Expanded Analogs of the Mannosidase Inhibitor Swainsonine
  作者：William H. Pearson、Erik J. Hembre

  DOI：10.1021/jo960609b

  日期：1996.1.1

  The indolizidine azasugar swainsonine (1) is an important inhibitor of mannosidase II and has shown antitumor and immunomodulatory activity. A comparison of the structure of swainsonine and D-mannopyranose shows that swainsonine lacks the C(4) hydroxymethine group of mannose. Ring-expanded quinolizidine analogs 4 of swainsonine were prepared where the ''missing'' hydroxymethine group was incorporated into the pyrrolidine ring of swainsonine between C(1) and C(8a). The quinolizidine analogs 4 resemble both D-mannopyranose and the related azasugar deoxymannojirimycin, a selective inhibitor of the glycoprotein processing enzyme mannosidase I. D-Arabinose was converted into the omega-halo azidoalkene 13, which was subjected to thermolysis, a strategy which had been successful in an earlier synthesis of swainsonine itself. Rather than the desired quinolizidine 4, the pyridinium ion 16 was produced. An alternate synthesis of all four C(9)/C(9a) diastereomers of 4 was developed which relied on the reductive double-alkylation of epoxides bearing remote azido and chloro groups. Thus, reduction of compounds 21 alpha, 21 beta, 26, and 27 resulted in the formation of the quinolizidines 22, 23, 28, and 29, which were deprotected to give the quinolizidine analogs of swainsonine (9S,9aR)-4, (9R,9aS)-4, (9S,9aS)-4, and (9R,9aR)-4, respectively. An alternate synthesis of(9R,9aR)-4 involving the reductive N-alkylation of a cyclic imine was also developed. None of the quinolizidines showed significant glycosidase activity in screens against mannosidases, glucosidases, or fucosidases. Speculation on the significance of these findings is presented.