Glenthenamines A-F: Enamine Pyranonaphthoquinones from the Australian Pasture Plant Derived Streptomyces sp. CMB-PB042.

Chemical investigations into solid phase cultivations of an Australian sheep station pasture plant derived Streptomyces sp. CMB-PB042 yielded the rare enamine naphthopyranoquinones BE-54238A ( 1 ) and BE-54238B ( 2 ), together with four new analogues, glenthenamines B-D ( 4 - 6 ) and F ( 8 ), and two handling artifacts, glenthenamines A ( 3 ) and E ( 7 ). Single-crystal X-ray analyses of 1 and 2 resolved configurational ambiguities in the scientific literature, while detailed spectroscopic analysis and biosynthetic considerations assigned structures inclusive of absolute configuration to 3 - 8 . We propose a plausible sequence of biosynthetic transformations linking structural and configurational features of 1 - 8 and apply a novel Schiff base "fishing" approach to detect a key deoxyaminosugar precursor. These enamine naphthopyranoquinones disclose a new P-gp inhibitory pharmacophore capable of reversing doxorubicin resistance in P-gp overexpressing colon carcinoma cells.