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Flavin‐dependent enzymes enable a broad range of redox transformations and generally act as monofunctional and stereoselective catalysts. Herein, we report the investigation of a multifunctional and non‐stereoselective FMN‐dependent oxidoreductase RubE7 from the rubrolone biosynthetic pathway. Our study outlines a single RubE7‐catalysed sequential reduction of three spatially distinct bonds in a tropolone ring and a reversible double‐bond reduction and dehydrogenation. The crystal structure of IstO (a RubE7 homologue) with 2.0 Å resolution reveals the location of the active site at the interface of two monomers, and the size of active site is large enough to permit both flipping and free rotation of the substrate, resulting in multiple nonselective reduction reactions. Molecular docking and site mutation studies demonstrate that His106 is oriented towards the substrate and is important for the reverse dehydrogenation reaction. [ABSTRACT FROM AUTHOR]

The Diels–Alder reactions of tropolone and its conjugate base with N‐methylmaleimide have been explored computationally and experimentally. Previous studies of the [4+2] cycloaddition under basic conditions show that both endo‐ and exo‐products are obtained in similar, but variable amounts. Density functional theory (ωB97X‐D) explorations of potential energy surfaces, and molecular dynamics trajectories show that the reaction involves an ambimodal transition state for the reaction of the ammonium tropolonate with N‐methylmaleimide, and that similar amounts of endo‐ and exo‐products are obtained. The thermal reaction, studied experimentally in detail here for the first time, is predicted to form the endo‐adduct through an ambimodal transition state. The exo‐adduct can be formed from the same transition state, but requires a hydrogen shift, that hinders this reaction dynamically. Longer reaction times give a small excess of the exo‐product, which is thermodynamically more stable. [ABSTRACT FROM AUTHOR]

The non‐canonical terpene cyclase AsR6 is responsible for the formation of 2E,6E,9E‐humulene during the biosynthesis of the tropolone sesquiterpenoid (TS) xenovulene A. The structures of unliganded AsR6 and of AsR6 in complex with an in crystallo cyclized reaction product and thiolodiphosphate reveal a new farnesyl diphosphate binding motif that comprises a unique binuclear Mg2+‐cluster and an essential K289 residue that is conserved in all humulene synthases involved in TS formation. Structure‐based site‐directed mutagenesis of AsR6 and its homologue EupR3 identify a single residue, L285/M261, that controls the production of either 2E,6E,9E‐ or 2Z,6E,9E‐humulene. A possible mechanism for the observed stereoselectivity was investigated using different isoprenoid precursors and results demonstrate that M261 has gatekeeping control over product formation. [ABSTRACT FROM AUTHOR]

Tropolone sesquiterpenoids (TS) are an intriguing family of biologically active fungal meroterpenoids that arise through a unique intermolecular hetero Diels–Alder (hDA) reaction between humulene and tropolones. Here, we report on the combinatorial biosynthesis of a series of unprecedented analogs of the TS pycnidione 1 and xenovulene A 2. In a systematic synthetic biology driven approach, we recombined genes from three TS biosynthetic gene clusters (pycnidione 1, xenovulene A 2 and eupenifeldin 3) in the fungal host Aspergillus oryzae NSAR1. Rational design of the reconstituted pathways granted control over the number of hDA reactions taking place, the chemical nature of the fused polyketide moiety (tropolono‐ vs. monobenzo‐pyranyl) and the degree of hydroxylation. Formation of unexpected monobenzopyranyl sesquiterpenoids was investigated using isotope‐feeding studies to reveal a new and highly unusual oxidative ring contraction rearrangement. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of two η5‐aminoborole complexes of germanium(II) from the reaction of a germole dianion with aminoboron dichlorides is reported. This reaction constitutes a remarkable example of a germole‐to‐borole transformation. The two aminoborole complexes of germanium(II) were fully characterized by multinuclear NMR spectroscopy, IR spectroscopy, HRMS, and, in one case, by X‐ray crystallography. The results of quantum‐mechanical calculations favor the electronic structure of a half‐sandwich complex of GeII over an ionic representation with a germanium dication stabilized by an aromatic aminoborole dianion. [ABSTRACT FROM AUTHOR]

Abstract: An organocatalyzed asymmetric [4+2]‐cycloaddition between tropolones and electron‐deficient dienophiles is presented. Complex and biologically interesting dihydrohomobarrelenone scaffolds are formed through a Diels–Alder reaction utilizing bifunctional Brønsted‐base catalysis, affording the corresponding bridged bicyclic cycloadducts in up to quantitative yields with good enantio‐ (up to 92 % ee) and diastereoselectivity (up to >20:1 d.r.). The synthetic value of the obtained products is explored by downstream transformations, including photoisomerizations, and their biological relevancy by in vivo testing in MCF‐7 cancer cells. [ABSTRACT FROM AUTHOR]

A tropolone group has been employed for the first time as an anchoring group for dye-sensitized solar cells (DSSCs). The DSSC based on a porphyrin, YD2-o-C8T, with a tropolone moiety exhibited a power-conversion efficiency of 7.7 %, which is only slightly lower than that observed for a reference porphyrin, YD2-o-C8, with a conventional carboxylic group. More importantly, YD2-o-C8T was found to be superior to YD2-o-C8 with respect to DSSC durability and binding ability to TiO2. These results unambiguously demonstrate that tropolone is a highly promising dye-anchoring group for DSSCs in terms of device durability as well as photovoltaic performance. [ABSTRACT FROM AUTHOR]

A series of directed knockout experiments, combined with an in vitro assay of pathway components, has elucidated for the first time the chemical steps involved in the biosynthesis of the tropolone class of fungal maleic anhydrides. The pathway involves the stepwise oxidation of aldehyde and methyl carbon atoms to form a 1,2-dicarboxylate. A hydrolase-catalyzed interconversion of this and the corresponding maleic anhydride, followed by decarboxylation of the diacid leads to the pathway's final product of stipitatic acid. [ABSTRACT FROM AUTHOR]

The correct interpretation is provided of how tunneling proceeds at low temperatures in the proton transfer Reactions (1) and (3) involving thiotropolone and tropolone (see the Arrhenius plots). It is also shown that the variational transition‐state theory calculations carried out by Jose and Datta (Angew. Chem.­ 2012, 124, 9523; Angew. Chem. Int. Ed.­ 2012, 51, 9389), as well as their conclusions regarding these two processes are erroneous. [ABSTRACT FROM AUTHOR]