抗肿瘤天然产物汉黄芩素的合成
收稿日期: 2016-04-27
修回日期: 2016-06-21
网络出版日期: 2016-08-10
基金资助
长江学者奖励计划、国家自然科学基金（Nos. 81520108030，81573318，81373301，1302658）、上海市重点学科建设（No. B906）和上海活性天然产物制备工程研究中心（No. 10DZ2251300）资助项目.
Synthesis of Wogonin, a Natural Product with Anticancer Activity
Received date: 2016-04-27
Revised date: 2016-06-21
Online published: 2016-08-10
Supported by
Project supported by the Professor of Chang Jiang Scholars Program, the National Natural Science Foundation of China (Nos. 81520108030, 81573318, 81373301, 1302658), the Shanghai Leading Academic Discipline Project (No. B906), the Shanghai Engineering Research Center for the Preparation of Bioactive Natural Products (No. 10DZ2251300).
汉黄芩素（wogonin，5，7-二羟基-8-甲氧基黄酮）是传统中草药黄芩的有效成分之一，其抗肿瘤活性显著，且对肿瘤细胞的杀伤作用有其独特的机制.目前报道的化学合成法大多总收率较低，反应条件苛刻或原料来源困难.笔者以2，4-二苄氧基-6-羟基苯乙酮与苯甲醛为原料，经Claisen-Schmidt缩合、氧化关环得到5，7-二苄氧基黄酮，通过对5，7-二苄氧基黄酮的8-位碘代、硼酸酯化和氧化从而高效引入8-位羟基，再经甲基化和脱苄基保护完成汉黄芩素的克级合成，总收率大于70%，且反应条件温和、无需柱层析，适合规模化生产.为该类化合物的进一步结构修饰、活性和机制研究提供了保障.
袁虎 , 叶霁 , 陈浩 , 赵增 , 李玉柱 , 张卫东 , 孙青龑 . 抗肿瘤天然产物汉黄芩素的合成[J]. 有机化学, 2016 , 36(12) : 2960 -2964 . DOI: 10.6023/cjoc201604057
Wogonin (5,7-dihydroxy-8-methoxyflavone) is an active component isolated from the Traditional Chinese Medicine (TCM) Huang Qin, which exhibits significant anti-tumor activity via a unique mechanism. The reported chemical synthesis of wogonin suffered either from low overall yield, harsh reaction conditions or from noncommercially available starting materials. In this paper, a new synthesis of wogonin was achieved via Claisen-Schmidt condensation, cyclization, iodination at C-8 position of flavone, borylation of sterically hindered aryl iodides, oxidation of boronic esters, methylation and debenzylation reaction using 2,4-dibenzyloxy-6-hydroxy phenylacetone and benzaldehyde as the starting materials, which provided gram-scale wogonin in >70% overall yield. The total synthesis employs mild reaction conditions and conventional flash column chromatography is not needed for purification, which makes it suitable for large-scale production. The efficient and flexible entry should offer opportunities for further modification and chemical biology investigations.
Key words： anticancer; wogonin; borylation; synthesis
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