有机化学 ›› 2024, Vol. 44 ›› Issue (9): 2862-2868.DOI: 10.6023/cjoc202403006 上一篇    下一篇

研究论文

防风中亥茅酚及亥茅酚苷的不对称合成

曾涛, 张曙盛, 付建国*(), 冯陈国*()   

  1. 上海中医药大学创新中药研究院 上海 201203
  • 收稿日期:2024-03-04 修回日期:2024-04-15 发布日期:2024-05-16
  • 通讯作者: 付建国, 冯陈国
  • 基金资助:
    国家自然科学基金(22271195); 国家自然科学基金(22301185); 上海市科学技术委员会(21ZR1482100); 上海市科学技术委员会(22ZR1458900); 上海市中央引导地方科技发展资金(YDZX20223100001004); 上海中医药大学有组织科研计划(2023YZZ01); 及上海中医药大学预算内(2021LK001)

Asymmetric Synthesis of Hamaudol and sec-O-Glucosylhamaudol in Saposhnikovia divaricata (Turcz.) Schischk

Tao Zeng, Shusheng Zhang, Jianguo Fu(), Chenguo Feng()   

  1. Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203
  • Received:2024-03-04 Revised:2024-04-15 Published:2024-05-16
  • Contact: Jianguo Fu, Chenguo Feng
  • Supported by:
    National Natural Science Foundation of China(22271195); National Natural Science Foundation of China(22301185); Science and Technology Commission of Shanghai Municipality(21ZR1482100); Science and Technology Commission of Shanghai Municipality(22ZR1458900); Shanghai Science and Technology Development Fund from Central Leading Local Government(YDZX20223100001004); Organizational Key R&D Program of Shanghai University of Traditional Chinese Medicine(2023YZZ01); Expenditure Budget Program of Shanghai University of Traditional Chinese Medicine(2021LK001)

色原酮类化合物作为中药防风中的主要成分具有广泛的生物活性, 其中代表性化合物亥茅酚和亥茅酚苷分别具有抗过敏和抗炎活性. 报道了一条亥茅酚及亥茅酚苷的不对称合成路线, 该路线主要利用Ca(OH)2促进酚烯醇与异戊烯醛发生aldol/环化串联反应, 高区域选择性地构建6/6/6三环核心骨架, 利用Jacobsen不对称环氧化反应实现3'位手性中心的构建, 以线性6步21%总收率实现亥茅酚的不对称合成, 以线性8步15%总收率完成了亥茅酚苷的不对称合成.

关键词: 防风, 色原酮, 亥茅酚, 亥茅酚苷, 不对称合成

Chromones from the traditional Chinese medicine Saposhnikovia divaricata (Turcz.) Schischk exhibit various biological activities, among which the representative compounds, hamaudol and sec-O-glucosylhamaudol, have anti-allergic and anti-inflammatory activities. A concise asymmetric synthesis of hamaudol and sec-O-glucosylhamaudol has been accomplished. The key strategies included the Ca(OH)2-catalyzed regioselective construction of 6/6/6 tricyclic skeleton by aldol reaction/annulation of phenolic enolate with 3-methyl-2-butenal and the construction of chiral centers in the 3'-position by Jacobsen's asymmetric epoxidation reaction. This strategy provided a concise and rapid approach to synthesize hamaudol (linear 6-steps and 21% overall yield) and sec-O-glucosylhamaudol (linear 8-steps and 15% overall yield) from the commercial reagent.

Key words: Saposhnikovia Divaricata (Turcz.) schischk, chromone, hamaudol, sec-O-glucosylhamaudol, asymmetric synthesis