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.