Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp ZQ4BG

Bioactive natural products from mangrove-derived actinomycetes are important sources for discovery of drug lead compounds. In this study, an extract prepared from culture of an actinomycete Streptomyces sp. ZQ4BG isolated from mangrove soils was found to have activity in inhibiting proliferation of glioma cells. Large culture of this mangrove actinomycete in Gause's liquid medium resulted in isolation of seven novel polyene-polyol macrolides, named as flavofungins III-IX (3-9), together with known flavofungins I (1) and II (2) and spectinabilin (10). Structures of these isolated compounds were elucidated by extensive NMR analyses and HRESIMS data. The stereochemical assignments were achieved by a combination of NOE information, universal NMR database, and chemical reactions including preparation of acetonide derivatives and Mosher esters. Flavofungins IV-VIII (4-8) are rare 32-membered polyene-polyol macrolides with a tetrahydrofuran ring, while flavofungin IX (9) represents the first example of this type of macrolide with a unique oxepane ring. Flavofungins I (1) and II (2) and spectinabilin (10) showed anti-glioma and antifungal activities.