Absolute configuration and protein tyrosine phosphatase 1B inhibitory activity of xanthoepocin, a dimeric naphtopyrone from Penicillium sp. IQ-429

Xanthoepocin, a photolabile antibiotic of Penicillium ochrochloron CBS 123823 with high activity against multiresistant gram-positive bacteria

“…The results can be found in the Additional file 1 : Material in Chapter 1. Via comparison with the available data from the literature (NMR and MS [ 11 , 24 ]) and interpretation of the newly recorded data, we could confirm the isolation of xanthoepocin from P. ochrochloron .…”

“…[ 5 – 10 ]) and a biosynthetic route was suggested [ 22 , 23 ]. Just recently, the absolute configuration was resolved [ 24 ]. So far, however, trigger factors leading to its production are completely unknown, and also the biological function of this widespread metabolite still remains in the dark.…”

Harnessing the Reactivity of Duclauxin toward Obtaining hPTP1B1–400 Inhibitors

“…Interaction of compounds 1−4, 5a, 6-7, and 8a−14a with residues of the WPD loop supports the hypothesis of an allosteric modulation (Figure 2D) in a similar way to xanthoepocin, which binds to hPTP1B 1−400 and disrupts the dynamics of the WPD loop (close-active/open-inactive), preventing the course of the hydrolysis reaction (Figure 2D). 13 Based on docking results, it is hypothesized that the allosteric modulation of hPTP1B 1−400 by azaphenalenones is driven by interaction with amino acids from the WPD loop, restricting the access of the substrate in a similar way than TCS401 and MSI-1436. 10,29,30 Semisynthetic Strategy to Access Duclauxin Derivatives: A Series.…”

“…1D and 2D NMR experiments were conducted in CDCl 3 . NMR instrumentation was a Bruker Ascend III 700 MHz NMR spectrometer equipped with a cryoprobe, operating at 700 MHz for 1 H and 175 MHz for 13 C, or a Bruker 500 Ascend equipped with an autosampler, running at 500 MHz for 1 H and 125 MHz for 13 C. Reactions were performed at room temperature (rt) in dry glassware and monitored by HPLC-UV using a Gemini-NX 5 μm particle size C 18 or Luna PFP columns (4.6 mm × 250 mm; Phenomenex, Torrance, CA). Reaction products were purified by using the corresponding semipreparative HPLC columns (10.0 mm × 250 mm).…”

“…IQ-429. 13 From the molecules listed above, duclauxin (1) is especially relevant, as it exhibits the best inhibitory activity (IC 50 = 35 inhibitor of hPTP1B 1−400 . 10 Even more, duclauxin (1) is the most abundant product in the extract of the fungus (up to 0.7g/ 10 g), which makes it suitable to be modified with the purpose of improving its biological properties as hPTP1B 1−400 inhibitor.…”