Totalsynthese und Strukturkorrektur des antibiotisch wirksamen Tetrapeptids GE81112A

Jürjens, Gerrit; Schuler, Sören M. M.; Kurz, Michael; Petit, Sylvain; Couturier, Cédric; Jeannot, Frédéric; Nguyen, Fabian; Wende, Raffael C.; Hammann, Peter; Wilson, Daniel N.; Bacqué, Eric; Pöverlein, Christoph; Bauer, Armin

doi:10.1002/ange.201805901

“…These observations corroborate the stereochemistry of the product of GetF to be (2 S ,3 R )‐3‐HyPip, which is in agreement with the results of recent biosynthetic studies [6,7] . In the meantime, researchers at Sanofi succeeded in the total synthesis of GE81112 A, which also confirmed this configurational assignment that resulted in a revision of the original structural proposal, postulating a (2 S ,3 S )‐configuration [18] …”

Section: Resultssupporting

confidence: 89%

“…[6,7] In the meantime, researchers at Sanofi succeeded in the total synthesis of GE81112 A, which also confirmed this configurational assignment that resulted in a revision of the original structural proposal, postulating a (2S,3S)-configuration. [18]…”

Section: Resultsmentioning

confidence: 99%

Stereoselective Syntheses of Deuterated Pipecolic Acids as Tools to Investigate the Stereoselectivity of the Hydroxylase GetF

Neis

¹

,

Xie

²

,

Krug

³

et al. 2022

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Members of the GE81112 family are interesting candidates for the development of antibiotics. The configuration of the OH group on the pipecolic acid moiety plays a pivotal role in antibiotic activity. To investigate the stereoselectivity of the corresponding hydroxylase GetF, involved in the biosynthetic pathway, we synthesized the two deuterium-labeled pipecolic acid diastereomers in a highly stereoselective fashion via chelate-enolate Claisen rearrangement. The stereochemical outcome of the enzymatic hydroxylation step could easily be determined by analysis of mass differences between the products.

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Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis

Ganesan

¹

,

Aldholmi

²

,

Ahmad

³

et al. 2022

Angewandte Chemie

2

0

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By limiting the nitrogen source to glutamic acid, we isolated cyclic peptides from Euglena gracilis containing asparagine and non-proteinogenic amino acids. Structure elucidation was accomplished through spectroscopic methods, mass spectrometry and chemical degradation. The euglenatides potently inhibit pathogenic fungi and cancer cell lines e.g., euglenatide B exhibiting IC 50 values of 4.3 μM in Aspergillus fumigatus and 0.29 μM in MCF-7 breast cancer cells. In an unprecedented convergence of non-ribosomal peptide synthetase and polyketide synthase assembly-line biosynthesis between unicellular species and the metazoan kingdom, euglenatides bear resemblance to nemamides from Caenorhabditis elegans and inhibited both producing organisms E. gracilis and C. elegans. By molecular network analysis, we detected over forty euglenatide-like metabolites in E. gracilis, E. sanguinea and E. mutabilis, suggesting an important biological role for these natural products.

show abstract

Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis

Ganesan

¹

,

Aldholmi

²

,

Ahmad

³

et al. 2022

View full text Add to dashboard Cite

By limiting the nitrogen source to glutamic acid, we isolated cyclic peptides from Euglena gracilis containing asparagine and non-proteinogenic amino acids. Structure elucidation was accomplished through spectroscopic methods, mass spectrometry and chemical degradation. The euglenatides potently inhibit pathogenic fungi and cancer cell lines e.g., euglenatide B exhibiting IC 50 values of 4.3 μM in Aspergillus fumigatus and 0.29 μM in MCF-7 breast cancer cells. In an unprecedented convergence of non-ribosomal peptide synthetase and polyketide synthase assembly-line biosynthesis between unicellular species and the metazoan kingdom, euglenatides bear resemblance to nemamides from Caenorhabditis elegans and inhibited both producing organisms E. gracilis and C. elegans. By molecular network analysis, we detected over forty euglenatide-like metabolites in E. gracilis, E. sanguinea and E. mutabilis, suggesting an important biological role for these natural products.

show abstract

Totalsynthese und Strukturkorrektur des antibiotisch wirksamen Tetrapeptids GE81112A

Cited by 3 publications

References 21 publications

Stereoselective Syntheses of Deuterated Pipecolic Acids as Tools to Investigate the Stereoselectivity of the Hydroxylase GetF

Stereoselective Syntheses of Deuterated Pipecolic Acids as Tools to Investigate the Stereoselectivity of the Hydroxylase GetF

Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis

Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis

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