Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (9): 2013-2018.DOI: 10.6023/cjoc201503049 Previous Articles     Next Articles

Notes

CytosporoneB的高效合成

吕超a, 李剑芳a,b, 徐洪蛟a, 沈月毛a   

  1. a 山东大学药学院 天然产物化学生物学教育部重点实验室 济南 250012;
    b 山东中医药大学药学院 济南 250355
  • 收稿日期:2015-03-30 修回日期:2015-05-04 出版日期:2015-09-25 发布日期:2015-05-06
  • 通讯作者: 沈月毛 E-mail:yshen@sdu.edu.cn
  • 基金资助:

    国家基础研究计划(973 项目, No. 2010CB833802)、国家自然科学基金(Nos. 81373304, 91313303, 81302666)、长江学者和创新团队发展计划(No. IRT13028)和国家杰出青年科学基金(No. 30325044)资助项目.

An Efficient Synthesis of Cytosporone B

Lü Chaoa, Li Jianfanga,b, Xu Hongjiaoa, Shen Yuemaoa   

  1. a Key Laboratory of Chemical Biology Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012;
    b School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355
  • Received:2015-03-30 Revised:2015-05-04 Online:2015-09-25 Published:2015-05-06
  • Supported by:

    Project supported by the National Basic Research Program (973 Program, No. 2010CB833802), the National Natural Science Foundation of China (Nos. 81373304, 91313303, 81302666), the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT13028) and the National Science Found for Distinguished Young Scholars of China (No. 30325044).

The fungal polyketide cytosporone B (Csn-B) displays diverse biological activities, and is an important small molecule probe for the studies on biological progress thus that its efficient synthesis attracts much attention. In this study, the commercial available 1-(3,5-dihydroxyphenyl)ethanone was used as starting material. After converting to benzyl ether, the product 1-(3,5-dibenzyloxyphenyl)ethanone was treated with sulfur powder and morpholine followed by hydrolysis in one pot to afford the key intermediate 3,5-dibenzyloxyphenylacetic acid via Willgerodt-Kindler reaction. Respectively, the 3,5-dibenzyloxyphenylacetic acid was converted to Csn-B or secocurvularin (67.3% overall yield) through esterification, Friedel-Crafts acylation reaction and deprotection procedures in 5 steps totally. Cytosporone A (Csn-A) was obtained in 65.3% yield through hydrolysis of Csn-B and cytosporone C (Csn-C) was provided in 64.0% yield via reduction-cyclization of Csn-B. Our synthetic approach to Csn-B and its derivatives has the advantages of short pathways, high yield, economical starting material, and is suitable for large-scale preparation.

Key words: polyketide, cytosporone B, small molecule probe, Willgerodt-Kindler reaction