有机化学 ›› 2020, Vol. 40 ›› Issue (6): 1571-1577.DOI: 10.6023/cjoc202001031 上一篇    下一篇

研究论文

白藜芦醇二聚体Quadrangularin A和Pallidol合成方法学研究

韩吉来a, 唐美麟a,c, 孙逊a,b   

  1. a 复旦大学药学院天然药物系 上海 201203;
    b 复旦大学中西医结合研究所 上海 200040;
    c 复旦大学生物医学研究院 上海 200433
  • 收稿日期:2020-01-23 修回日期:2020-03-13 发布日期:2020-04-10
  • 通讯作者: 孙逊 E-mail:sunxunf@shmu.edu.cn
  • 基金资助:
    国家自然科学基金(No.81673297)、上海市科委基金(No.17431902500)和中国博士后基金(No.2019M651384)资助项目.

Study on the Total Synthesis of Resveratrol Dimers Quadrangularin A and Pallidol

Han Jilaia, Tang Meilina,c, Sun Xuna,b   

  1. a Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai 201203;
    b The Institutes of Integrative Medicine of Fudan University, Shanghai 200040;
    c Institutes of Biomedical Sciences, Fudan University, Shanghai 200433
  • Received:2020-01-23 Revised:2020-03-13 Published:2020-04-10
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. 81673297), the Shanghai Committee of Science and Technology (No. 17431902500), and the China Postdoctoral Science Foundation (No. 2019M651384).

研究了白藜芦醇二聚体quadrangularin A(3)和pallidol(4)的全合成新方法学,设计了以廉价易得的3,5-二甲氧基苯乙腈(5)和3,5-二甲氧基苯甲醛(6)为原料,经9步反应得到天然产物quadrangularin A(3),总收率为2.6%;经11步反应得到天然产物pallidol(4),总收率为1.3%.其中,利用Knoevenagel反应在室温无需无水无氧条件下,简单高效地引入A、B两个对称或非对称芳环,拓展了二苯乙烯基多样性骨架结构中间体7,产率达98%以上,改善了文献报道中非对称结构拓展受限,产率低,操作复杂等问题.此外,通过巧妙构建4-烯醛骨架结构的关键中间体9,可高效地构筑C、D芳环,为拓展A、B、C和D芳环多样性结构的白藜芦醇类二聚体提供了新思路.所合成的中间体及天然产物结构均经1H NMR,13C NMR,HRMS表征确证.

关键词: 白藜芦醇二聚体, 傅克反应, 格氏试剂加成, 全合成

This paper has focused on developing a novel methodology for the total synthesis of quadrangularin A (3) and pallidol (4). These two resveratrol dimers have been obtained from the inexpensive materials of 3,5-dimethoxybenzaldehyde (5) and 3,5-dimethoxybenzaldehyde (6) within 9 steps and 11 steps with total yields of 2.6% and 1.3%, respectively. The stilbene skeleton constructed by two symmetric or asymmetric aromatic rings (A and B) has been synthesized simply through Knoevenagel reaction under mild conditions with yield of more than 98%, which expanded the diversity of stilbene skeleton (7), and addressed the problems of limited expansion of asymmetric structure, low yield and complex operation. In addition, the key intermediate of 4-enaldehyde skeleton structure (9) could be used to construct aromatic rings of C and D efficiently, which has thrown light on the expansion of resveratrol dimers with aromatic ring A, B, C and D in diversity structure. All the intermediates and natural products have been characterized by 1H NMR, 13C NMR, and HRMS.

Key words: resveratrol oligomer, Friedel-Crafts reaction, Grignard regent addition reaction, total synthesis