Author contributions and conflict of interest Daniel Braga performed research, analyzed data (molecular biology, malachite green assay, mass spectrometry) and contributed to writing the manuscript, Daniel Last performed research and analyzed data (structure elucidation, Fno assay, biogas plant studies), Mahmudul Hasan performed research (CofC/D enzyme assays), Huijuan Guo performed research and analyzed data (structure elucidation), Daniel Leichnitz performed research (chemical synthesis), Zerrin Uzum performed research (microscopy), Ingrid Richter performed research (microscopy), Felix Schalk performed research (cofE constructs), Christine Beemelmanns designed research, acquired funding, analyzed data (structure elucidation, synthesis) and edited the manuscript, Christian Hertweck designed research, acquired funding and edited the manuscript, Gerald Lackner designed the study, acquired funding and wrote the original manuscript. The authors declare no conflict of interest.

The discovery of six new, highly substituted tropolone alkaloids, rubterolones A-F, from Actinomadura sp. 5-2, isolated from the gut of the fungus-growing termite Macrotermes natalensis is reported. Rubterolones were identified by using fungus-bacteria challenge assays and a HRMS-based dereplication strategy, and characterised by NMR and HRMS analyses and by X-ray crystallography. Feeding experiments and subsequent chemical derivatisation led to a first library of rubterolone derivatives (A-L). Genome sequencing and comparative analyses revealed their putative biosynthetic pathway, which was supported by feeding experiments. This study highlights how gut microbes can present a prolific source of secondary metabolites.

Trifluoromethanesulfonic acid in acetonitrile was found to efficiently catalyze Friedel-Crafts alkylations of 1,2,4-trimethoxybenzene with a variety of simple or functionalized aldehydes to provide di- or triarylmethanes in high yields. The operationally simple protocol allowed a short synthesis of the phenylpropanoid natural product (-)-tatarinoid C establishing its absolute configuration. Under the developed reaction conditions a benzylic alcohol instead of an aldehyde also underwent reactions with 1,2,4-trimethoxybenzene and other nucleophiles to afford unsymmetrically substituted compounds.

Activating chemical bonds through external triggers and understanding the underlying mechanism are at the heart of developing molecules with catalytic and switchable functions. Thermal, photochemical, and electrochemical bond activation pathways are useful for many chemical reactions. In this Article, a series of Ru(II) complexes containing a bidentate and a tripodal ligand were synthesized. Starting from all-pyridine complex 1(2+), the pyridines were stepwise substituted with "click" triazoles (2(2+)-7(2+)). Whereas the thermo- and photoreactivity of 1(2+) are due to steric repulsion within the equatorial plane of the complex, 3(2+)-6(2+) are reactive because of triazoles in axial positions, and 4(2+) shows unprecedented photoreactivity. Complexes that feature neither steric interactions nor axial triazoles (2(2+) and 7(2+)) do not show any reactivity. Furthermore, a redox-triggered conversion mechanism was discovered in 1(2+), 3(2+), and 4(2+). We show here ligand design principles required to convert a completely inert molecule to a reactive one and vice versa, and provide mechanistic insights into their functioning. The results presented here will likely have consequences for developing a future generation of catalysts, sensors, and molecular switches.

Communication is essential for all domains of life. Bacteria use a plethora of small molecules to sense and orchestrate intra- and interspecies communication. Within this review, we will discuss different groups of signalling molecules, including autoinducers, virulence factors and morphogenic substances. On selected examples, we will shortly discuss their ecological roles and biosynthetic proposals. The major part of this review will focus on a systematic overview of the different synthetic methods applied towards the synthesis of signalling molecules and derivatives thereof. The described examples highlight the importance of organic synthetic method development and diversity-oriented total syntheses for structure verification, structure-function analysis and target identification.