Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China , Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology , Qingdao 266200, China.
J Nat Prod. 2018 Jan 26;81(1):211-215. doi: 10.1021/acs.jnatprod.7b00917. Epub 2018 Jan 12.
We reported previously the discovery of the potent antimalarial 40-membered macrolide bastimolide A (1) from the tropical marine cyanobacterium Okeania hirsute. Continued investigation has led to the discovery of a new analogue, bastimolide B (2), a 24-membered polyhydroxy macrolide with a long aliphatic chain and unique terminal tert-butyl group. Its complete structure was determined by a combination of extensive spectroscopic methods and comparative analysis of its methanolysis products with those of bastimolide A. A methanolysis mechanism for bastimolide A is proposed, and one unexpected isomerization product of the C2-C3 double bond, 2-(E)-bastimolide A (3), was obtained. Bastimolide B (2) showed strong antimalarial activity against chloroquine-sensitive Plasmodium falciparum strain HB3. A preliminary investigation of the structure-activity relationship based on six analogues revealed the importance of the double bond as well as the 1,3-diol and 1,3,5-triol functionalities.
我们曾报道过从热带海洋蓝细菌 Okeania hirsute 中发现具有强大抗疟作用的 40 元大环内酯 bastimolide A（1）。进一步的研究发现了一种新的类似物 bastimolide B（2），它是一种具有长脂肪链和独特末端叔丁基的 24 元聚羟基大环内酯。其完整结构通过广泛的光谱方法结合与 bastimolide A 的甲醇解产物的比较分析来确定。提出了 bastimolide A 的甲醇解机制，并获得了 C2-C3 双键的一个意外异构化产物 2-(E)-bastimolide A（3）。bastimolide B（2）对氯喹敏感的恶性疟原虫 HB3 株表现出强烈的抗疟活性。基于六种类似物的结构-活性关系的初步研究表明，双键以及 1,3-二醇和 1,3,5-三醇官能团的重要性。
