Synthesis of l-β-(6-azulenyl)alanine and the fluorescent actin disruptor (6-azuleno)chalasin H

Maurice Hauser; Katharina Schmidt; Leonard Beiderwieden; Cheng Yi; Kjeld Gerdes; Markus Kalesse; Jennifer Gerke; Theresia E. Stradal; Russell J. Cox

doi:10.1039/d5ra04702a

Synthesis of l-β-(6-azulenyl)alanine and the fluorescent actin disruptor (6-azuleno)chalasin H

Maurice Hauser, Katharina Schmidt, Leonard Beiderwieden, Cheng Yi, Kjeld Gerdes, Markus Kalesse, Jennifer Gerke, Theresia E. Stradal, Russell J. Cox^*

^*Corresponding author for this work

Helmholtz Centre for Infection Research (HZI)

Research output: Contribution to journal › Article › Research › peer review

Abstract

l-β-(6-Azulenyl)alanine was synthesised for the first time. Supplementation of this compound to Pyricularia grisea ΔpyiA led to the biosynthesis of the unnatural (6-azuleno)chalasin H and its 1′-bromo congener that have unprecedented natural product skeletons and that are both fluorescent and highly cytotoxic, with IC₅₀ of 0.18 μg mL⁻¹vs. L929 cells in vitro. Actin staining showed that both compounds are potent, but partially reversible, actin disruptors.

Original language	English
Pages (from-to)	26048-26051
Number of pages	4
Journal	RSC Advances
Volume	15
Issue number	32
DOIs	https://doi.org/10.1039/d5ra04702a
Publication status	Published - 22 Jul 2025

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering

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title = "Synthesis of l-β-(6-azulenyl)alanine and the fluorescent actin disruptor (6-azuleno)chalasin H",

abstract = "l-β-(6-Azulenyl)alanine was synthesised for the first time. Supplementation of this compound to Pyricularia grisea ΔpyiA led to the biosynthesis of the unnatural (6-azuleno)chalasin H and its 1′-bromo congener that have unprecedented natural product skeletons and that are both fluorescent and highly cytotoxic, with IC50 of 0.18 μg mL−1vs. L929 cells in vitro. Actin staining showed that both compounds are potent, but partially reversible, actin disruptors.",

author = "Maurice Hauser and Katharina Schmidt and Leonard Beiderwieden and Cheng Yi and Kjeld Gerdes and Markus Kalesse and Jennifer Gerke and Stradal, {Theresia E.} and Cox, {Russell J.}",

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T1 - Synthesis of l-β-(6-azulenyl)alanine and the fluorescent actin disruptor (6-azuleno)chalasin H

AU - Hauser, Maurice

AU - Schmidt, Katharina

AU - Beiderwieden, Leonard

AU - Yi, Cheng

AU - Gerdes, Kjeld

AU - Kalesse, Markus

AU - Gerke, Jennifer

AU - Stradal, Theresia E.

AU - Cox, Russell J.

PY - 2025/7/22

Y1 - 2025/7/22

N2 - l-β-(6-Azulenyl)alanine was synthesised for the first time. Supplementation of this compound to Pyricularia grisea ΔpyiA led to the biosynthesis of the unnatural (6-azuleno)chalasin H and its 1′-bromo congener that have unprecedented natural product skeletons and that are both fluorescent and highly cytotoxic, with IC50 of 0.18 μg mL−1vs. L929 cells in vitro. Actin staining showed that both compounds are potent, but partially reversible, actin disruptors.

AB - l-β-(6-Azulenyl)alanine was synthesised for the first time. Supplementation of this compound to Pyricularia grisea ΔpyiA led to the biosynthesis of the unnatural (6-azuleno)chalasin H and its 1′-bromo congener that have unprecedented natural product skeletons and that are both fluorescent and highly cytotoxic, with IC50 of 0.18 μg mL−1vs. L929 cells in vitro. Actin staining showed that both compounds are potent, but partially reversible, actin disruptors.

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U2 - 10.1039/d5ra04702a

DO - 10.1039/d5ra04702a

M3 - Article

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VL - 15

SP - 26048

EP - 26051

JO - RSC Advances

JF - RSC Advances

IS - 32

ER -

Synthesis of l-β-(6-azulenyl)alanine and the fluorescent actin disruptor (6-azuleno)chalasin H

Abstract

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