Total Syntheses of Depsipeptide Elastase Inhibitors YM-47141 and YM-47142 with use of Ylide Protection and Coupling Methods

Wasserman, Harry H.; Chen, Jyun-Hung; Xia, Mingde

doi:10.1021/ja9840302

Cited by 35 publications

(10 citation statements)

References 28 publications

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“…They showed potent HLE inhibition with IC 50 values of 1.5 µM and 3.0 µM, respectively (Orita et al, 1995;Yasumuro et al, 1995). Their total synthesis has also been reported (Wasserman et al, 1999;Wasserman et al, 2000).…”

Section: Polypeptides Of the Bacteriummentioning

confidence: 95%

The Natural Polypeptides as Significant Elastase Inhibitors

et al. 2020

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Human neutrophil elastase (HNE) is a major cause of the destruction of tissues in cases of several different chronic andinflammatory diseases. Overexpression of the elastase enzyme plays a significant role in the pathogenesis of various diseases including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome, rheumatoid arthritis, the rare disease cyclic hematopoiesis (or cyclic neutropenia), infections, sepsis, cystic fibrosis, myocardial ischemia/reperfusion injury and asthma, inflammation, and atherosclerosis. Human neutrophil elastase is secreted by human neutrophils due to different stimuli. Medicine-based inhibition of the over-activation of neutrophils or production and activity of elastase have been suggested to mend inflammatory diseases. Although the development of new elastase inhibitors is an essential strategy for treating the different inflammatory diseases, it has been a challenge to specifically target the activity of elastase because of its overlapping functions with those of other serine proteases. This review article highlights the reported natural polypeptides as potential inhibitors of elastase enzyme. The mechanism of action, structural features, and activity of the polypeptides have also been correlated wherever they were available.

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Section: Polypeptides Of the Bacteriummentioning

confidence: 95%

The Natural Polypeptides as Significant Elastase Inhibitors

et al. 2020

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“…Finally, bearing in mind the interest of 1,2,3-tricarbonyl compounds (vicinal tricarbonyl compounds, VCTs) both as structural fragments of protease inhibitors [31] and synthetic intermediates [32–33], we also explored briefly their direct preparation from compounds 2 , together with their application to the synthesis of nitrogen heterocycles bearing a peptide side chain. We discovered that treatment of representative aziridines 2 with perchloric acid in a THF–water reaction medium led to the isolation of the corresponding compounds 11 , which were then transformed into pyrazines 12 and quinoxalines 13 via straightforward cyclocondensation reactions with ethylenediamine and o -phenylenediamine, respectively (Scheme 6 and Table 3).…”

Section: Resultsmentioning

confidence: 99%

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

Huck

González

Cuesta

et al. 2016

Beilstein J. Org. Chem.

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SummaryA sequential three-component process is described, starting from 3-arylmethylene-2,5-piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions. Their transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was also achieved in a single step.

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“…1,2,3-Vicinal tricarbonyl systems have been shown to serve as potent electrophiles in organic synthesis (Wasserman et al, 1993;Wasserman et al, 1999). In this paper we report the structure of a tricarbonyl system, (I), having the terminal carbonyl group as masked functionality, which was obtained from the rearrangement of 1-(4 H -methoxy-phenyl)-3-acetoxy-4,4-bis(methylthio)azetidin-2-one (II) in quantitative yield.…”

Section: Commentmentioning

confidence: 98%