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

Journal of Natural Products
2022.0

Abstract

Chemical investigations into solid phase cultivations of an Australian sheep station pasture plant derived <i>Streptomyces</i> sp. CMB-PB042 yielded the rare enamine naphthopyranoquinones BE-54238A (<b>1</b>) and BE-54238B (<b>2</b>), together with four new analogues, glenthenamines B-D (<b>4</b>-<b>6</b>) and F (<b>8</b>), and two handling artifacts, glenthenamines A (<b>3</b>) and E (<b>7</b>). Single-crystal X-ray analyses of <b>1</b> and <b>2</b> resolved configurational ambiguities in the scientific literature, while detailed spectroscopic analysis and biosynthetic considerations assigned structures inclusive of absolute configuration to <b>3</b>-<b>8</b>. We propose a plausible sequence of biosynthetic transformations linking structural and configurational features of <b>1</b>-<b>8</b> 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.

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