有机化学 ›› 2015, Vol. 35 ›› Issue (1): 137-143.DOI: 10.6023/cjoc201407002 上一篇    下一篇

研究论文

基于[3+2]环加成反应的氮杂螺[3,4]环辛烷的合成

王雯, 陆秀宏, 董肖椿, 赵伟利   

  1. 复旦大学药学院 上海 201203
  • 收稿日期:2014-07-01 修回日期:2014-09-19 出版日期:2015-01-25 发布日期:2014-09-25
  • 通讯作者: 董肖椿, 赵伟利 E-mail:xcdong@fudan.edu.cn;zhaoweili@fudan.edu.cn
  • 基金资助:

    教育部博士点基金(No. 20130071110071)、上海市自然科学基金(No. 12ZR1403300)和上海市科技支撑(No. 13431900102)资助项目.

Synthesis of Azaspiro[3.4]octanes via [3+2] Cycloaddition

Wang Wen, Lu Xiuhong, Dong Xiaochun, Zhao Weili   

  1. School of Pharmacy, Fudan University, Shanghai 201203
  • Received:2014-07-01 Revised:2014-09-19 Online:2015-01-25 Published:2014-09-25
  • Supported by:

    Project supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20130071110071), the Shanghai Municipal Natural Science Foundation (No. 12ZR1403300), the Shanghai Municipal Science & Technology Pillar Program for Bio-pharmaceuticals (No. 13431900102).

哌嗪、吗啉是小分子药物中常见的结构片段, 2,6-二氮杂螺[3,4]环辛烷和2-氧-6-氮杂螺[3,4]环辛烷等四元螺环化合物作为其类似物, 在药物化学领域具有良好的应用前景. 本研究以廉价易得的丙二酸二乙酯或丙烯酸乙酯为起始原料, 经[3+2]环加成反应, 可便捷高效地完成6-苄基-2,6-二氮杂螺[3,4]环辛烷和2-氧-6-氮杂螺[3,4]环辛烷克级水平的合成.

关键词: 2,6-二氮杂螺[3,4]环辛烷, 2-氧-6-氮杂螺[3,4]环辛烷, [3+2]环加成

Piperazine and morpholine are common modules in drugs. Design and synthesis of their surrogates may help to explore the chemical and patent space in medicinal chemistry. In this article, through [3+2] cycloaddition, the improved synthesis of 6-benzyl-2,6-diazaspiro[3.4]octane oxalate and 2-oxa-6-azaspiro[3.4]octane as substitutes of piperazine and morpholine was provided, respectively. Multi-gram quantities of the compounds could be easily obtained in relatively high yields.

Key words: 2,6-diazaspiro[3,4]octane, 2-oxa-6-azaspiro[3,4]octane, [3+2] cycloaddition