Palmarumycin B6类似物的合成及杀蚊活性
收稿日期: 2021-09-13
修回日期: 2021-09-29
网络出版日期: 2022-02-24
基金资助
国家自然科学基金(21772229)
Synthesis and Larvicidal Activity of Palmarumycin B6 Analogues
Received date: 2021-09-13
Revised date: 2021-09-29
Online published: 2022-02-24
Supported by
National Natural Science Foundation of China(21772229)
为了提高天然产物Palmarumycin B6的生物活性, 通过取代四氢萘酮烯醇醚和1,8-二羟基萘的缩酮化反应以及吡啶重铬酸盐和过氧叔丁醇参与的苄位氧化反应作为关键步骤完成了多个Palmarumycin B6 A环含氯和含氟类似物的合成, 它们的结构经过1H NMR, 13C NMR和HR-ESI-MS的表征. 对它们的杀蚊活性进行了评价, 结果表明6-氯-5-羟基- 2,3-二氢-4H-螺[萘-1,2'-萘[1,8-de][1,3]-二噁烷]-4-酮(4m)和6-氟-5-羟基-2,3-二氢-4H-螺[萘-1,2'-萘[1,8-de][1,3]-二噁烷]-4-酮(4i)是活性最好的化合物,对白纹伊蚊的LC50值为11.51和23.25 µg/mL,它们可以作为先导结构进行进一步结构优化. 在6位的卤素原子、5-羟基和4-羰基对该类Palmarumycin B6类似物的杀蚊活性起到了关键作用.
关键词： 螺二萘; Palmarumycin B6; 缩酮化反应; 苄位氧化反应; 杀蚊活性
刘鑫磊 , 许磊川 , 安鑫鲲 , 蒋家珍 , 王明安 . Palmarumycin B6类似物的合成及杀蚊活性[J]. 有机化学, 2022 , 42(2) : 519 -525 . DOI: 10.6023/cjoc202109018
In order to improve the biological activity of naturally occurring Palmarumycin B6, the synthesis of Palmarumycin B6 chlorine- and fluorine-containing analogues at A ring has been achieved via ketalization of substituted 1-tetralone enol ether with 1,8-dihydroxynaphthalene and the benzyl oxidation involving pyridinium dichromate and t-BuOOH as the key steps. Their structures were fully characterized by 1H NMR, 13C NMR, and HR-ESI-MS data. Their larvicidal activities were evaluated and showed that 6-chloro-5-hydroxy-2,3-dihydro-4H-spiro[naphthalene-1,2'-naphtho[1,8-de]-[1,3]dioxin]-4-one (4m) and 6-fluoro-5-hydroxy-2,3-dihydro-4H-spiro[naphthalene-1,2'-naphtho[1,8-de][1,3]dioxin]-4-one (4i) were the most active compounds with the LC50 values of 11.51 and 23.25 µg/mL against Aedes albopictus, and they would be the potential lead structure to be optimized. The halogen atoms at C-6, 5-hydroxy and 4-carbonyl play a critical role for the larvicidal activities of this type of Palmarumycin B6 analogues.
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