28 Jun 13:50
by Jinhai Yu,
Qiaoyu Zhang,
Beibei Zhao,
Tianhang Wang,
Yu Zheng,
Binju Wang,
Yan Zhang,
Xiaoqiang Huang
A dual bio-/photocatalytic system has been developed for achieving previously elusive diastereo- and enantioselective radical lactonizations. By integrating directed evolution and photoinduced single-electron oxidation, we repurposed engineered ene-reductases to steer non-natural radical C−O formations giving a diverse array of enantioenhanced 5- and 6-membered lactones with vicinal stereocenters, part of which bears a quaternary stereocenter.
Abstract
Repurposing enzymes to catalyze non-natural asymmetric transformations that are difficult to achieve using traditional chemical methods is of significant importance. Although radical C−O bond formation has emerged as a powerful approach for constructing oxygen-containing compounds, controlling the stereochemistry poses a great challenge. Here we present the development of a dual bio-/photo-catalytic system comprising an ene-reductase and an organic dye for achieving stereoselective lactonizations. By integrating directed evolution and photoinduced single electron oxidation, we repurposed engineered ene-reductases to steer non-natural radical C−O formations (one C−O bond for hydrolactonizations and lactonization-alkylations while two C−O bonds for lactonization-oxygenations). This dual catalysis gave a new approach to a diverse array of enantioenhanced 5- and 6-membered lactones with vicinal stereocenters, part of which bears a quaternary stereocenter (up to 99 % enantiomeric excess, up to 12.9 : 1 diastereomeric ratio). Detailed mechanistic studies, including computational simulations, uncovered the synergistic effect of the enzyme and the externally added organophotoredox catalyst Rh6G.
28 Jun 13:45
Nature Catalysis, Published online: 26 June 2024; doi:10.1038/s41929-024-01191-8
This Editorial deals with scientific language in research papers, considering the causes — as well as the problems — associated with the use of hyperbolic statements.
28 Jun 12:18
by Ru Jiang
Nature Synthesis, Published online: 27 June 2024; doi:10.1038/s44160-024-00584-8
Combining a natural decarboxylase and an artificial metathase, a microbial cell factory is created that enables the synthesis of cycloalkenes from fatty diacids in a whole-cell hybrid biocatalytic cascade process.
28 Jun 12:18
by Zhi Zou
Nature Synthesis, Published online: 27 June 2024; doi:10.1038/s44160-024-00575-9
Artificial metalloenzymes are useful catalysts in synthesis, but their use in cells is a challenge. Now, the development of an engineered whole-cell enzymatic cascade, which converts glucose-derived fatty diacids into cycloalkenes, is reported. The cascade process combines a decarboxylase with an artificial metalloenzyme that catalyses an abiotic olefin metathesis reaction.
24 Jun 06:09
by Abir Das,
Subramani Kumaran,
Harihara Subramanian Ravi Sankar,
J. Richard Premkumar,
Basker Sundararaju
In this study, we showcase cobalt-catalyzed asymmetric dearomatization of indoles with aryl amides, achieving remarkable enantioinduction and exceptional regioselectivity. This dual catalytic strategy, which integrates photocatalyst and cobalt, represents a pioneering approach in asymmetric C−H bond functionalization. Through detailed experimental investigations and DFT calculations, we present a plausible mechanism to elucidate the reaction pathway.
Abstract
In this study, we unveil a novel method for the asymmetric dearomatization of indoles under cobalt/photoredox catalysis. By strategically activating C−H bonds of amides and subsequent migratory insertion of π-bonds present in indole as reactive partner, we achieve syn-selective tetrahydro-5H-indolo[2,3-c]isoquinolin-5-one derivatives with excellent yields and enantiomeric excesses of up to >99 %. The developed method operates without a metal oxidant, relying solely on oxygen as the oxidant and employing an organic dye as a photocatalyst under irradiation. Control experiments and stoichiometric studies elucidate the reversible nature of the enantiodetermining C−H activation step, albeit not being rate-determining. This study not only expands the horizon of cobalt-catalyzed asymmetric C−H bond functionalization, but also showcases the potential synergy between cobalt and photoredox catalysis in enabling asymmetric synthesis of complex molecules.
24 Jun 06:08
by Ming-Ya Teng,
De-Yang Liu,
Shi-Yu Mao,
Xu Wu,
Jia-Hao Chen,
Ming-Yu Zhong,
Fan-Rui Huang,
Qi-Jun Yao,
Bing-Feng Shi
We report an efficient protocol for chiral dihydroisoquinolone-fused indolines through a cobaltaphotoredox catalyzed enantioselective C−H activation/dearomatization of indoles. Mechanistic studies indicate the excited photocatalyst was quenched by cobalt(II) species in the presence of Salox ligand. The stoichiometric reactions of cobaltacycle intermediate suggest the irradiation of light also play a critical role in the dearomatization step.
Abstract
Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger of photocatalysis and transition-metal-catalyzed asymmetric C−H activation as an efficient and sustainable method for the construction of chiral molecules remains elusive and challenging. Herein, we develop a cobalt-catalyzed enantioselective C−H activation reaction enabled by visible-light photoredox catalysis, providing a synergistic catalytic strategy for the asymmetric dearomatization of indoles with high levels of enantioselectivity (96 % to >99 % ee). Mechanistic studies indicate that the excited photocatalyst was quenched by divalent cobalt species in the presence of Salox ligand, leading to the formation of catalytically active chiral Co(III) complex. Moreover, stoichiometric reactions of cobaltacycle intermediate with indole suggest that the irradiation of visible light also play a critical role in the dearomatization step.
19 Jun 15:11
by Eric M. Koehn, Albert Lang, Allison Flores, Claudia Lambert, and Judith Klinman
ACS Chemical Biology
DOI: 10.1021/acschembio.4c00198
19 Jun 09:36
by Kyle F., Biegasiewicz
Nitrogen-containing compounds are valuable synthetic intermediates and targets in nearly every chemical industry. While methods for nitrogen-carbon and nitrogen-heteroatom bond formation have primarily relied on nucleophilic nitrogen atom reactivity, molecules containing nitrogen-halogen bonds allow for reactivity through electrophilic or radical mechanisms at the nitrogen center. Despite the growing synthetic utility of nitrogen-halogen-containing compounds, selective catalytic strategies for their synthesis are largely underexplored. We recently discovered that the vanadium-dependent haloperoxidase (VHPO) class of enzymes are a suitable biocatalyst platform for nitrogen-halogen bond formation. Herein, we show that VHPOs perform selective halogenation of a range of substituted benzamidine hydrochlorides to produce the corresponding N’-halobenzimidamides. This biocatalytic platform is applied to the synthesis of 1,2,4-oxadiazoles from the corresponding N-acylbenzamidines in high yield and with excellent chemoselectivity. Finally, the synthetic applicability of this biotechnology is demonstrated in an extension to nitrogen-nitrogen bond formation and the chemoenzymatic synthesis of the Duchenne muscular dystrophy treatment, ataluren.
16 Jun 18:07
by Ebbin Joseph,
Jon A Tunge
Catalytic allylations have emerged as versatile processes for assembling C−C or C−heteroatom bonds. Traditionally, noble transition metals like Pd, Rh, or Ir have been extensively employed for these processes. However, recent sustainable catalytic strategies have shifted towards utilizing base metals as catalysts. Consequently, this review outlines the breakthroughs in cobalt-catalyzed allylic alkylations, emphasizing their noteworthy advancements in the field.
Abstract
The rising demand and financial costs of noble transition metal catalysts have emphasized the need for sustainable catalytic approaches. Over the past few years, base-metal catalysts have emerged as ideal candidates to replace their noble-metal counterparts because of their abundance and easiness of handling. Despite the significant advancements achieved with precious transition metals, earth-abundant cobalt catalysts have emerged as efficient alternatives for allylic substitution reactions. In this review, allylic alkylations at sp3-carbon centers mediated by cobalt will be discussed, with a special focus on the mechanistic features, scope, and limitations.
16 Jun 17:19
by Antonio Angelastro
Nature Synthesis, Published online: 14 June 2024; doi:10.1038/s44160-024-00563-z
Aldehyde-bearing proteins are shown to be suitable substrates for Horner–Wadsworth–Emmons reactions. Applying this process to proteins and glycoproteins enables site-specific bioconjugation with tunable reaction kinetics.
14 Jun 16:09
by Bradley L., Pentelute
The remarkable efficiency with which enzymes catalyze small molecule reactions has driven their widespread application in organic chemistry. Here, we employ automated fast-flow solid-phase synthesis to access full-length enzymes without restrictions on the number and structure of non-canonical amino acids incorporated. We demonstrate the total syntheses of Fe-dependent Bacillus subtilis myoglobin (BsMb) and sperm whale myoglobin (SwMb), which displayed excellent enantioselectivity and yield in carbene transfer reactions. Absolute control over enantioselectivity in styrene cyclopropanation was achieved using L- and D-BsMb mutants which delivered each enantiomer of cyclopropane product in identical and opposite enantiomeric enrichment. BsMb mutants outfitted with non-canonical amino acids were used to facilitate detailed structure-activity relationship studies, revealing a previously unrecognized hydrogen-bonding interaction as the primary driver of enantioselectivity in styrene cyclopropanation.
12 Jun 09:48
by Xingchen Dong,
Ziyang Qiu,
Zixiao Wang,
Jiaqi Li,
Weijun Qin,
Jingshuang Dang,
Wenqin Zhou,
Guoqing Jia,
Yashao Chen,
Changhao Wang
A silver(I)-containing i-motif DNA hybrid catalyst enables the catalysis of Diels–Alder reactions with high reactivity and excellent enantioselectivity, in which the catalytic center of copper(II) ion specifically coordinates with one nitrogen atom of adenine and two nearby phosphate-oxygen atoms in the loop region.
Abstract
The inherent chiral structures of DNA serve as attractive scaffolds to construct DNA hybrid catalysts for valuable enantioselective transformations. Duplex and G-quadruplex DNA-based enantioselective catalysis has made great progress, yet novel design strategies of DNA hybrid catalysts are highly demanding and atomistic analysis of active centers is still challenging. DNA i-motif structures could be finely tuned by different cytosine-cytosine base pairs, providing a new platform to design DNA catalysts. Herein, we found that a human telomeric i-motif DNA containing cytosine-silver(I)-cytosine (C-Ag+-C) base pairs interacting with Cu(II) ions (i-motif DNA(Ag+)/Cu2+) could catalyze Diels–Alder reactions with full conversions and up to 95 % enantiomeric excess. As characterized by various physicochemical techniques, the presence of Ag+ is proved to replace the protons in hemiprotonated cytosine-cytosine (C : C+) base pairs and stabilize the DNA i-motif to allow the acceptance of Cu(II) ions. The i-motif DNA(Ag+)/Cu2+ catalyst shows about 8-fold rate acceleration compared with DNA and Cu2+. Based on DNA mutation experiments, thermodynamic studies and density function theory calculations, the catalytic center of Cu(II) ion is proposed to be located in a specific loop region via binding to one nitrogen-7 atom of an unpaired adenine and two phosphate-oxygen atoms from nearby deoxythymidine monophosphate and deoxyadenosine monophosphate, respectively.
12 Jun 08:34
by Elie Dolgin
Nature, Published online: 11 June 2024; doi:10.1038/d41586-024-01717-x
The same mRNA technology that quickly brought the world a vaccine for COVID-19 is now showing promise as a bespoke therapy for cancer.
10 Jun 08:38
by Meihui Guan, Ting Yin, Yue Wang, Huanran Miao, Ge Zhang, and Qian Zhang
ACS Catalysis
DOI: 10.1021/acscatal.4c02211
10 Jun 07:59
by Shobhit S. Chaturvedi, Santiago Vargas, Pujan Ajmera, and Anastassia N. Alexandrova
Journal of the American Chemical Society
DOI: 10.1021/jacs.4c03914
10 Jun 07:57
by Benjamin T. Boyle
Nature, Published online: 06 June 2024; doi:10.1038/s41586-024-07628-1
Unlocking carbene reactivity by metallaphotoredox α-elimination
04 Jun 11:08
by Shubhanshu Jain, Felipe Ospina, and Stephan C. Hammer
JACS Au
DOI: 10.1021/jacsau.4c00247
04 Jun 09:52
by Katrina Krämer
Nature, Published online: 31 May 2024; doi:10.1038/d41586-024-01664-7
Tech heavyweights brawl over whether research needs to be published to count as science. Plus, the first recipient of a gene-edited pig liver is ‘doing very well’ and how Viking-age hunters took down the world’s biggest animal.
01 Jun 09:06
by Xin Liu, Sheng Xu, Heyu Chen, and Yang Yang
ACS Catalysis
DOI: 10.1021/acscatal.4c02752
31 May 09:40
Four parties hammer out agreement filled with bad news for scientists
30 May 14:36
by Francesco Zamberlan
Nature Catalysis, Published online: 29 May 2024; doi:10.1038/s41929-024-01176-7
A boronic enzyme
28 May 21:58
by Donghui Xing
Nature Communications, Published online: 27 May 2024; doi:10.1038/s41467-024-48873-2
Transition-metal catalyzed cross-electrophile coupling (XEC) is a powerful tool for the construction of molecules but XEC between carbon electrophile and chlorosilanes to access organosilicon compounds remains underdeveloped. Here the authors disclose a highly efficient cobalt-catalyzed cross-electrophile alkynylation of a broad range of unactivated chlorosilanes with alkynyl sulfides as a stable and practical alkynyl electrophiles.
25 May 18:38
by Zhixi Zhu,
Qinru Hu,
Yi Fu,
Yingjia Tong,
Zhi Zhou
Highly stereoselective Michael addition of cyclic ketones to nitroolefins was promoted by a designer artificial enzyme harboring a catalytic pyrrolidine residue through enamine catalysis. Diverse chiral γ-nitroketones were prepared by this efficient biocatalytic strategy for ketone functionalization in a study highlighting the utility of artificial enzymes for new-to-nature reactions.
Abstract
Consistent introduction of novel enzymes is required for developing efficient biocatalysts for challenging biotransformations. Absorbing catalytic modes from organocatalysis may be fruitful for designing new-to-nature enzymes with novel functions. Herein we report a newly designed artificial enzyme harboring a catalytic pyrrolidine residue that catalyzes the asymmetric Michael addition of cyclic ketones to nitroolefins through enamine activation with high efficiency. Diverse chiral γ-nitro cyclic ketones with two stereocenters were efficiently prepared with excellent stereoselectivity (up to 97 % e.e., >20 : 1 d.r.) and good yield (up to 86 %). This work provides an efficient biocatalytic strategy for cyclic ketone functionalization, and highlights the usefulness of artificial enzymes for extending biocatalysis to further non-natural reactions.
23 May 20:35
by Tobias Vornholt, Mojmír Mutný, Gregor W. Schmidt, Christian Schellhaas, Ryo Tachibana, Sven Panke, Thomas R. Ward, Andreas Krause, and Markus Jeschek
ACS Central Science
DOI: 10.1021/acscentsci.4c00258
23 May 20:30
by Xiangdong Li
Nature Chemistry, Published online: 23 May 2024; doi:10.1038/s41557-024-01535-8
The σ-type cyclopropenium cations (CPCs) are unstable species and currently underdeveloped. Now, an iodine(III)-based cyclopropenyl transfer reagent has been developed, which can generate electrophilic cyclopropenyl-gold(III) species as equivalents of σ-type CPCs. The synthetic potential has been demonstrated by the transfer of σ-type CPCs to terminal alkynes and vinylboronic acids.
21 May 05:54
by Chintan Soni, Noam Prywes, Matthew Hall, Malavika A. Nair, David F. Savage, Alanna Schepartz, and Abhishek Chatterjee
ACS Central Science
DOI: 10.1021/acscentsci.3c01557
18 May 21:19
by Ziyan Zhang and Vladimir Gevorgyan
Chemical Reviews
DOI: 10.1021/acs.chemrev.3c00869
18 May 21:10
by Laura Tiessler-Sala,
Jean-Didier Maréchal,
Agustí Lledós
A computational modeling approach is applied to rationalize the impact of streptavidin mutations and length of the biotion cofactor on the enantioselective Suzuki-Miyaura synthesis of binaphthyls by means of an Artificial Metalloenzyme built employing the streptavidin-biotin technology. The integrative computational approach includes DFT calculations, protein-ligand dockings and molecular dynamics simulations.
Abstract
An Artificial Metalloenzyme (ArM) built employing the streptavidin-biotin technology has been used for the enantioselective synthesis of binaphthyls by means of asymmetric Suzuki-Miyaura cross-coupling reactions. Despite its success, it remains a challenge to understand how the length of the biotin cofactors or the introduction of mutations to streptavidin leads the preferential synthesis of one atropisomer over the other. In this study, we apply an integrated computational modeling approach, including DFT calculations, protein-ligand dockings and molecular dynamics to rationalize the impact of mutations and length of the biotion cofactor on the enantioselectivities of the biaryl product. The results unravel that the enantiomeric differences found experimentally can be rationalized by the disposition of the first intermediate, coming from the oxidative addition step, and the entrance of the second substrate. The work also showcases the difficulties facing to control the enantioselection when engineering ArM to catalyze enantioselective Suzuki-Miyaura couplings and how the combination of DFT calculations, molecular dockings and MD simulations can be used to rationalize artificial metalloenzymes.
18 May 20:57
by Juan D Villada,
Jadab Majhi,
Valentin Lehuédé,
Michelle E Hendricks,
Katharina Neufeld,
Veronica Tona,
Rudi Fasan
A first enantioselective method for the cyclopropanation of difluorinated olefins is presented. Using engineered myoglobin-based catalysts in combination with diazoacetonitrile as the carbene precursor, the present method enables the production of different fluorinated cyclopropanes with high yields and high enantioselectivity.
Abstract
Fluorinated cyclopropanes are highly desired pharmacophores in drug discovery owing to the rigid nature of the cyclopropane ring and the beneficial effects of C−F bonds on the pharmacokinetic properties, cell permeability, and metabolic stability of drug molecules. Herein a biocatalytic strategy for the stereoselective synthesis of mono-fluorinated and gem-difluoro cyclopropanes is reported though the use of engineered myoglobin-based catalysts. In particular, this system allows for a broad range of gem-difluoro alkenes to be cyclopropanated in the presence of diazoacetonitrile with excellent diastereo and enantiocontrol (up to 99 : 1 d.r. and 99 % e.e.), thereby enabling a transformation not currently accessible with chemocatalytic methods. The synthetic utility of the present approach is further exemplified through the gram-scale synthesis of a key gem-difluorinated cyclopropane intermediate useful for the preparation of fluorinated bioactive molecules.
16 May 07:52
by Simon Larsen, Joseph A. Adewuyi, Kolle E. Thomas, Jeanet Conradie, Yoann Rousselin, Gaël Ung, and Abhik Ghosh
Inorganic Chemistry
DOI: 10.1021/acs.inorgchem.4c00483