Glenthenamines A–F: Enamine pyranonaphthoquinones from the Australian pasture plant-derived Streptomyces sp. CMB-PB042

12 October 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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 1–2 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 naphthopyranoquinone disclose a new P-gp inhibitory pharmacophore capable of reversing doxorubicin resistance in P-gp overexpressing colon carcinoma cells.

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.