Title |
Shornephine A: Structure, Chemical Stability, and P‑Glycoprotein Inhibitory Properties of a Rare Diketomorpholine from an Australian Marine-Derived Aspergillus sp.
|
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Published in |
Journal of Organic Chemistry, September 2014
|
DOI | 10.1021/jo501501z |
Pubmed ID | |
Authors |
Zeinab G. Khalil, Xiao-cong Huang, Ritesh Raju, Andrew M. Piggott, Robert J. Capon |
Abstract |
Chemical analysis of an Australian marine sediment-derived Aspergillus sp. (CMB-M081F) yielded the new diketomorpholine (DKM) shornephine A (1) together with two known and one new diketopiperazine (DKP), 15b-β-hydroxy-5-N-acetyladreemin (2), 5-N-acetyladreemin (3), and 15b-β-methoxy-5-N-acetyladreemin (4), respectively. Structure elucidation of 1-4 was achieved by detailed spectroscopic analysis, supported by chemical degradation and derivatization, and biosynthetic considerations. The DKM (1) underwent a facile (auto) acid-mediated methanolysis to yield seco-shornephine A methyl ester (1a). Our mechanistic explanation of this transformation prompted us to demonstrate that the acid-labile and solvolytically unstable DKM scaffold can be stabilized by N-alkylation. Furthermore, we demonstrate that at 20 μM shornephine A (1) is a noncytotoxic inhibitor of P-glycoprotein-mediated drug efflux in multidrug-resistant human colon cancer cells. |
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