Enzyme catalysis: Five isomers of aza-tryptophan and the corresponding series of cyclic Aza-tryptophan-proline dipeptides were tested as unnatural substrates for three well-known indole-prenylating enzymes, FgaPT2, CdpNPT, and FtmPT1. Most substrates were found to produce prenylated products, which revealed isomer-dependent regioselectivity and a previously unreported class of cationic N-prenyl pyridinium products.

Abstract

Aza-substitution, the replacement of aromatic CH groups with nitrogen atoms, is an established medicinal chemistry strategy for increasing solubility, but current methods of accessing functionalized azaindoles are limited. In this work, indole-alkylating aromatic prenyltransferases (PTs) were explored as a strategy to directly functionalize azaindole-substituted analogs of natural products. For this, a series of aza-L-tryptophans (Aza-Trp) featuring N-substitution of every aromatic CH position of the indole ring and their corresponding cyclic Aza-L-Trp-L-proline dipeptides (Aza-CyWP), were synthesized as substrate mimetics for the indole-alkylating PTs FgaPT2, CdpNPT, and FtmPT1. We then demonstrated most of these substrate analogs were accepted by a PT, and the regioselectivity of each prenylation was heavily influenced by the position of the N-substitution. Remarkably, FgaPT2 was found to produce cationic N-prenylpyridinium products, representing not only a new substrate class for indole PTs but also a previously unobserved prenylation mode. The discovery that nitrogenous indole bioisosteres can be accepted by PTs thus provides access to previously unavailable chemical space in the search for bioactive indolediketopiperazine analogs.

Dim the lights: Single-atom Pt/TiO₂ sites catalyse the photooxidation of anthracene even below the titania band gap.

Abstract

Single-atom catalysts (SACs) often show exceptionally high performance per metal loading. Besides benefiting from a better atom utilisation, the metal-support interaction is more pronounced in SACs compared to traditional nanoparticle catalysts. Thus, using SACs in photochemical conversions is of great advantage where the rapid reactions often depend on the synergistic interaction of the active site with the photoactive support. Here we show the importance of this interaction by maximizing the active site/support interface using SACs. As an example, we examine the oxidation reaction of anthracene to anthracene-9,10-endoperoxide (EPO) in the presence of 0.1 wt% Pt/TiO₂. Our SACs give a six-fold improvement compared to dense packed nanoparticle catalysts (TOF=113 mMol Anthracene g_Pt ⁻¹ min^-−1 for the SAC). We attribute this to the synergy between the active site and the support. Moreover, we show that photocatalytic conversion is possible with photons of lower energy (2.7 eV) than the bandgap of pristine TiO₂ (E_g=3.0–3.2 eV) thanks to organic doping of the metal oxide.

Allenes are valuable and versatile building blocks in organic chemistry. Numerous elegant transformations based on the catalytic synthesis of allenes have been established. This review mainly focuses on the recent advancements in nickel-catalyzed synthesis of allenes, including the reaction with propargylic derivatives, 1,3-enynes, 1,3-diynes, terminal alkynes, alkenyl halides, and allenyl electrophiles. The mechanistic investigations and synthetic challenges will be discussed.

Abstract

Allenes are one of the most important functional groups in organic chemistry, featuring unique physical and chemical properties. They are not only the key scaffolds present in natural products, pharmaceutical molecules, and advanced functional materials, but also the valuable and versatile building blocks for the construction of various complex and bioactive molecules in organic synthesis. Accordingly, benefiting from the rapid development of transition metal catalysis, numerous remarkable and efficient approaches for the synthesis of allenes from readily available chemicals have been established in the past decades. In this brief review, we focus on the recent advancements in nickel-catalyzed synthesis of allenes. These transformations are divided into two categories according to the types of reactions and sorted further by starting materials. Moreover, a concise discussion of the limitations and potential areas of improvement in this field is also provided, which would give an inspiration for future study on allene synthesis.

Many known enzymes sample huge protein conformational space, hampering structural characterization by X-ray crystallography, and preventing thus the understanding of their catalytic mechanisms. In this review, we outline that the combination of reconstructed ancestral enzymes with unconvertible substrate analogues is becoming a powerful strategy to decipher the challenging mechanisms of enzyme catalysis.

Abstract

Environmentally friendly industrial and biotech processes greatly benefit from enzyme-based technologies. Their use is often possible only when the enzyme-catalytic mechanism is thoroughly known. Thus, atomic-level knowledge of a Michaelis enzyme-substrate complex, revealing molecular details of substrate recognition and catalytic chemistry, is crucial for understanding and then rationally extending or improving enzyme-catalyzed reactions. However, many known enzymes sample huge protein conformational space, often preventing complete structural characterization by X-ray crystallography. Moreover, using a cognate substrate is problematic since its conversion into a reaction product in the presence of the enzyme will prevent the capture of the enzyme-substrate conformation in an activated state. Here, we outlined how to deal with such obstacles, focusing on the recent discovery of a Renilla-type bioluminescence reaction mechanism facilitated by a combination of engineered ancestral enzyme and the availability of a non-oxidizable luciferin analogue. The automated ancestral sequence reconstructions using FireProt^ASR provided a thermostable enzyme suited for structural studies, and a stable luciferin analogue azacoelenterazine provided a structurally cognate chemical incapable of catalyzed oxidation. We suggest that an analogous strategy can be applied to various enzymes with unknown catalytic mechanisms and poor crystallizability.

Pig Liver Esterase and Novozym® 435 showed good selectivity for the enzymatic kinetic resolution of cyclic carbonates. Several glycerol-derived carbonates were converted reaching er values of up to 99 : 1. Scalability of the reaction and recyclability of Novozym® 435 were demonstrated. Bioactive products were synthesized in good yields (81–89 %) and selectivity (90 : 10–94 : 6 er) using chiral carbonates as building blocks.

Abstract

The biocatalytic kinetic resolution of cyclic carbonates derived from glycerol is reported. A selection of 26 esterases and lipases was tested for the asymmetric hydrolysis of the model substrate (epichlorohydrin carbonate) in aqueous medium. Among them, Pig Liver Esterase and Novozym® 435 showed the best selectivity with E=38 and 49, respectively. Both enzymes were employed for the conversion of 12 glycerol derivatives under optimized conditions. The resolution of halogenated carbonates afforded the unconverted enantiomer in up to >99 : 1 er. Furthermore, Novozym® 435 was successfully recycled 10 times without significant loss of activity. Upscaling and isolation of the chiral carbonate was also demonstrated. Subsequent conversion of this chiral building block allowed the direct one-pot synthesis of (S)-Guaifenesin, (S)-Mephenesin and (S)-Chlorphenesin in up to 89 % yield and 94 : 6 er.

The Front Cover illustrates an artwork design for showcasing the developed bifunctional NiRe/SAPO-11 catalyst along with “KHON”, the masked dance drama in Thailand. In their Research Article, A. Srifa and co-workers designed the Re nanoparticles decorated on Ni/SAPO-11 catalyst for an economically combined process of direct triglycerides hydro-deoxygenation and isomerization into low-cold flow diesel. The diesel production comprising iso-alkanes components with proper catalyst lifetime and low carbon deposition are attributed to the fabricated active Ni with nanosized Re on bimodal SAPO-11 features with large distribution of Lewis acidic sites. It′s interesting to note that the cold-flow properties of liquid product are in the range of winter diesel standards. More information can be found in the Research Article by A. Srifa co-workers.

Heptanol oxidation: Melamine modification of commercial activated carbon can greatly tune the performance of Pt−Bi catalysts in n-heptanol oxidation. C₃N₄-modified AC favors the formation of PtBi alloy in comparison to N-doped AC, and consequently boosts the activity and selectivity to heptanoic acid.

Abstract

Different bimetallic platinum and bismuth catalysts supported on melamine-modified activated carbon (AC) are designed by a co-impregnation method. Through controlling the activation temperatures of the melamine−AC mixture, a series of N-doped and C₃N₄-modified AC (N−AC and C₃N₄−AC) are prepared. Combined powder X-ray diffractions, X-ray photoelectron spectroscopic, and high-angle annual dark-field scanning transmission electron microscopic studies demonstrate that the introduction of C₃N₄ favors the formation of PtBi alloy and leads to increased particle sizes in comparison to the pristine and N-doped AC-supported bimetallics. The catalytic performance of the developed catalysts is evaluated in the oxidation of n-heptanol oxidation in a batch mode using O₂ as the oxidant. PtBi/C₃N₄−AC exhibits significantly boosted activity as well as selectivity to heptanoic acid as compared with the other catalysts. A high yield of heptanoic acid of 69 % can be achieved under the optimized reaction conditions. Furthermore, our work points to the PtBi alloy as the most active sites for the alcohol oxidation. Catalyst deactivation occurs in the cycling tests, mainly due to the collapse of the alloy phase and likely the decrease in particle sizes.

Tetrazine-Norbornene ligation through inverse electron-demand Diels-Alder reaction has been employed as a novel strategy to immobilize a peptide-based catalyst onto different mesoporous silica supports. Functionalized silica monoliths as well as silica particles in packed bed reactors have been applied in the enantioselective flow catalysis of the addition reaction between ß-nitrostyrene and n-butanal.

Abstract

Organocatalysis via the enamine mechanism developed to one of the most relevant tools in carbonyl chemistry and is widely used in asymmetric organic synthesis. In this work, a strategy is presented to conveniently immobilize a peptide-based catalyst on silica supports for use in continuous flow catalysis reactions. A set of different porous silica supports is investigated spanning from mesoporous silica particles with defined pore sizes suitable for packed bed column reactors to silica monoliths with hierarchical meso-macropore spaces. While the silica supports are functionalized with norbornene entities, the peptide-based organocatalyst is modified with a tetrazine moiety, enabling the immobilization via inverse electron-demand Diels-Alder (IEDDA) reaction. The ligation results in catalyst loadings up to 0.2 mmol g^-1, without compromising the mesopore network. The catalytic activity of the materials is proven by the asymmetric C−C coupling reaction of n-butanal to ß-nitrostyrene proceeding in high yield and enantioselectivity in both batch and continuous flow setups.

A tetraaryl Co(II) square planar complex was recently reported via sodium-mediated cobaltation of pentafluorobenzene, while analogue structures with other ortho-substituted arenes remained elusive. Through a combination of DFT calculations, electronic structure and energy decomposition analyses we show that the formation of such complexes depends on the right balance between intramolecular X⋅⋅⋅X and Na⋅⋅⋅X (X=H, F, Cl, Br) interactions.

Abstract

The sodium-mediated cobaltation of pentafluorobenzene using the bimetallic base [NaCo(HMDS)₃] (HMDS=N(SiMe₃)₂) has been reported to afford a novel tetraaryl Co(II) square planar complex. Yet, the preparation of analogue structures with 1,2,3,4-tetrafluorobenzene, 1,3,5-trichlorobenzene, and 1,4-dibromo-2,5-difluorobenzene remains elusive. While the metalation step proceeds leading to stable [NaCo(HMDS)₂Ar] species, the ligand redistribution process to afford the tetraaryl Co(II) square planar complexes does not take place. Herein we report a density functional theory study in combination with electronic structure and energy decomposition analyses to shed light on the electronic and steric requirements to afford such complexes. Our findings show that the formation of the Co(II) square planar complexes depends on the right balance between intramolecular X⋅⋅⋅X and Na⋅⋅⋅X (X=H, F, Cl, Br) interactions. The latter further induces a ‘seesaw effect’, whereby the aryl ligand acts as a ‘seesaw’ allowing two X atoms in ortho positions to interdependently interact with Na. Only by considering both attractive and repulsive Na(X)⋅⋅⋅X interactions, the correct stability of the square planar complexes observed in experiments can be predicted computationally. We envision these insights to guide the rational design of novel square planar metal complexes for C−C coupling, a field that is still dominated by scarce and expensive precious metals.

Structurally ordered Rh₃Sn₂ intermetallic catalysts with a high selectivity of 95.1 % in the hydrogenation of 4-nitrostyrene to 4-aminostyrene were reported. Density functional theory calculation reveals that the Sn atoms assisted the adsorption of 4-nitrostyrene via nitro group and Rh₃Sn₂ intermetallics facilitated the hydrogenation on nitro group.

Abstract

The selective reduction of functionalized nitroarenes to aniline is a promising strategy to produce industrially vital aniline intermediates, while achieving high selectivity is challenging. Here, we reported the synthesis of structurally ordered Rh₃Sn₂ intermetallic catalysts that exhibited a high selectivity of 95.1 % in the hydrogenation of 4-nitrostyrene to 4-aminostyrene. Density functional theory calculation reveals that the adsorption of nitrostyrene through the nitro group on Rh₃Sn₂ (110) surface are great improved with the addition of the Sn atom. In addition, a significant electronic effect is formed between Rh and Sn by charge transfer that makes the Rh₃Sn₂ intermetallic compound more favorable for the hydrogenation of nitro group.