Bastimolide A, a potent antimalarial polyhydroxy macrolide from the marine cyanobacterium Okeania hirsuta

TitleBastimolide A, a potent antimalarial polyhydroxy macrolide from the marine cyanobacterium Okeania hirsuta
Publication TypeJournal Article
Year of Publication2015
AuthorsShao C.L, Linington RG, Balunas M.J, Centeno A., Boudreau P., Zhang C., Engene N, Spadafora C., Mutka T.S, Kyle D.E, Gerwick L, Wang C.Y, Gerwick WH
JournalJournal of Organic Chemistry
Volume80
Pagination7849-7855
Date Published2015/08
Type of ArticleArticle
ISBN Number0022-3263
Accession NumberWOS:000360103000002
Keywordsartemisinin; lyngbya-majuscula; macrolactone; plasmodium-falciparum malaria; stereochemistry
Abstract

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 H-1 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 mu 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.

DOI10.1021/acs.joc.5b01264
Short TitleJ. Org. Chem.
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