Expanding the Rubterolone Family: Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans

Huijuan Guo; René Benndorf; Stefanie König; Daniel Leichnitz; Christiane Weigel; Gundela Peschel; Patrick Berthel; Marcel Kaiser; Christoph Steinbeck; Oliver Werz; Michael Poulsen; Christine Beemelmanns

doi:10.1002/chem.201802066

Expanding the Rubterolone Family: Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans

Huijuan Guo, René Benndorf, Stefanie König, Daniel Leichnitz, Christiane Weigel, Gundela Peschel, Patrick Berthel, Marcel Kaiser, Christoph Steinbeck, Oliver Werz, Michael Poulsen, Christine Beemelmanns^*

^*Corresponding author for this work

Ecology and Evolution

Abstract

We characterized two key biosynthetic intermediates of the intriguing rubterolone family (tropolone alkaloids) that contain a highly reactive pyran moiety (in equilibrium with the hydrolyzed 1,5-dione form) and undergo spontaneous pyridine formation in the presence of primary amines. We exploited the intrinsic reactivity of the pyran moiety and isolated several new rubterolone derivatives, two of which contain a unique thiazolidine moiety. Three rubterolone derivatives were chemically modified with fluorescence and biotin tags using peptide coupling and click reaction. Overall, eight derivatives were fully characterized by HRMS/MS and 1D and 2D NMR spectroscopy and their antimicrobial, cytotoxic, anti-inflammatory and antiparasitic activities evaluated.

Original language	English
Journal	Chemistry - A European Journal
Volume	24
Issue number	44
Pages (from-to)	11319-11324
ISSN	0947-6539
DOIs	https://doi.org/10.1002/chem.201802066
Publication status	Published - 2018

Keywords

Biosynthetic pathway
Chemical probes
Natural products
Polyketides
Tropolone alkaloids

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10.1002/chem.201802066

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title = "Expanding the Rubterolone Family: Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans",

abstract = "We characterized two key biosynthetic intermediates of the intriguing rubterolone family (tropolone alkaloids) that contain a highly reactive pyran moiety (in equilibrium with the hydrolyzed 1,5-dione form) and undergo spontaneous pyridine formation in the presence of primary amines. We exploited the intrinsic reactivity of the pyran moiety and isolated several new rubterolone derivatives, two of which contain a unique thiazolidine moiety. Three rubterolone derivatives were chemically modified with fluorescence and biotin tags using peptide coupling and click reaction. Overall, eight derivatives were fully characterized by HRMS/MS and 1D and 2D NMR spectroscopy and their antimicrobial, cytotoxic, anti-inflammatory and antiparasitic activities evaluated.",

keywords = "Biosynthetic pathway, Chemical probes, Natural products, Polyketides, Tropolone alkaloids",

author = "Huijuan Guo and Ren{\'e} Benndorf and Stefanie K{\"o}nig and Daniel Leichnitz and Christiane Weigel and Gundela Peschel and Patrick Berthel and Marcel Kaiser and Christoph Steinbeck and Oliver Werz and Michael Poulsen and Christine Beemelmanns",

year = "2018",

doi = "10.1002/chem.201802066",

language = "English",

volume = "24",

pages = "11319--11324",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "44",

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TY - JOUR

T1 - Expanding the Rubterolone Family

T2 - Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans

AU - Guo, Huijuan

AU - Benndorf, René

AU - König, Stefanie

AU - Leichnitz, Daniel

AU - Weigel, Christiane

AU - Peschel, Gundela

AU - Berthel, Patrick

AU - Kaiser, Marcel

AU - Steinbeck, Christoph

AU - Werz, Oliver

AU - Poulsen, Michael

AU - Beemelmanns, Christine

PY - 2018

Y1 - 2018

N2 - We characterized two key biosynthetic intermediates of the intriguing rubterolone family (tropolone alkaloids) that contain a highly reactive pyran moiety (in equilibrium with the hydrolyzed 1,5-dione form) and undergo spontaneous pyridine formation in the presence of primary amines. We exploited the intrinsic reactivity of the pyran moiety and isolated several new rubterolone derivatives, two of which contain a unique thiazolidine moiety. Three rubterolone derivatives were chemically modified with fluorescence and biotin tags using peptide coupling and click reaction. Overall, eight derivatives were fully characterized by HRMS/MS and 1D and 2D NMR spectroscopy and their antimicrobial, cytotoxic, anti-inflammatory and antiparasitic activities evaluated.

AB - We characterized two key biosynthetic intermediates of the intriguing rubterolone family (tropolone alkaloids) that contain a highly reactive pyran moiety (in equilibrium with the hydrolyzed 1,5-dione form) and undergo spontaneous pyridine formation in the presence of primary amines. We exploited the intrinsic reactivity of the pyran moiety and isolated several new rubterolone derivatives, two of which contain a unique thiazolidine moiety. Three rubterolone derivatives were chemically modified with fluorescence and biotin tags using peptide coupling and click reaction. Overall, eight derivatives were fully characterized by HRMS/MS and 1D and 2D NMR spectroscopy and their antimicrobial, cytotoxic, anti-inflammatory and antiparasitic activities evaluated.

KW - Biosynthetic pathway

KW - Chemical probes

KW - Natural products

KW - Polyketides

KW - Tropolone alkaloids

U2 - 10.1002/chem.201802066

DO - 10.1002/chem.201802066

M3 - Journal article

C2 - 29846024

AN - SCOPUS:85050605010

SN - 0947-6539

VL - 24

SP - 11319

EP - 11324

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 44

ER -

Expanding the Rubterolone Family: Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans

Abstract

Keywords

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