Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania hirsuta

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• 作者：Chang-Lun Shao ; Roger G. Linington ; Marcy J. Balunas ; Argelis Centeno ; Paul Boudreau ; Chen Zhang ; Niclas Engene ; Carmenza Spadafora ; Tina S. Mutka ; Dennis E. Kyle ; Lena Gerwick ; Chang-Yun Wang ; William H. Gerwick
• 刊名：Journal of Organic Chemistry
• 出版年：2015
• 出版时间：August 21, 2015
• 年：2015
• 卷：80
• 期：16
• 页码：7849-7855
• 全文大小：341K
• ISSN：1520-6904

文摘

Bastimolide A (1), a polyhydroxy macrolide with a 40-membered ring, was isolated from a new genus of the tropical marine cyanobacterium Okeania hirsuta. This novel macrolide was defined by spectroscopy and chemical reactions to possess one 1,3-diol, one 1,3,5-triol, six 1,5-diols, and one tert-butyl group; however, the relationships of these moieties to one another were obscured by a highly degenerate ¹H NMR spectrum. Its complete structure and absolute configuration were therefore unambiguously determined by X-ray diffraction analysis of the nona-p-nitrobenzoate derivative (1d). Pure bastimolide A (1) showed potent antimalarial activity against four resistant strains of Plasmodium falciparum with IC₅₀ values between 80 and 270 nM, although with some toxicity to the control Vero cells (IC₅₀ = 2.1 渭M), and thus represents a potentially promising lead for antimalarial drug discovery. Moreover, rigorous establishment of its molecular arrangement gives fresh insight into the structures and biosynthesis of cyanobacterial polyhydroxymacrolides.