The selective addition of water Resch, Verena; Hanefeld, Ulf
Catalysis science & technology,
2015, Letnik:
5, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Water is omnipresent and essential. Yet at the same time it is a rather unreactive molecule. The direct addition of water to C&z.dbd;C double bonds is therefore a challenge not answered convincingly. ...In this perspective we critically evaluate the selectivity and the applicability of the different catalytic approaches for water addition reactions: homogeneous, heterogeneous and bio-catalytic. Here we would like to discuss how to speed up water addition and even make it selective.
Water is omnipresent and unreactive. How to speed up water addition and even make it selective are highlighted in this perspective.
Alkaloids are not only one of the most intensively studied classes of natural products, their wide spectrum of pharmacological activities also makes them indispensable drug ingredients in both ...traditional and modern medicine. Among the methods for their production, biotechnological approaches are gaining importance, and biocatalysis has emerged as an essential tool in this context. A number of chemo-enzymatic strategies for alkaloid synthesis have been developed over the years, in which the biotransformations nowadays take an increasingly 'central' role. This review summarises different applications of biocatalysis in the asymmetric synthesis of alkaloids and discusses how recent developments and novel enzymes render innovative and efficient chemo-enzymatic production routes possible.
Abstract
To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread occurred in multiple pandemic waves characterized ...by the emergence of new SARS-CoV-2 variants. Here we report a sequence and structural-bioinformatics analysis to estimate the effects of amino acid substitutions on the affinity of the SARS-CoV-2 spike receptor binding domain (RBD) to the human receptor hACE2. This is done through qualitative electrostatics and hydrophobicity analysis as well as molecular dynamics simulations used to develop a high-precision empirical scoring function (ESF) closely related to the linear interaction energy method and calibrated on a large set of experimental binding energies. For the latest variant of concern (VOC), B.1.1.529 Omicron, our Halo difference point cloud studies reveal the largest impact on the RBD binding interface compared to all other VOC. Moreover, according to our ESF model, Omicron achieves a much higher ACE2 binding affinity than the wild type and, in particular, the highest among all VOCs except Alpha and thus requires special attention and monitoring.
Organofluorine compounds have become important building blocks for a broad range of advanced materials, polymers, agrochemicals, and increasingly for pharmaceuticals. Despite tremendous progress ...within the area of fluorination chemistry, methods for the direct introduction of fluoroalkyl-groups into organic molecules without prefunctionalization are still highly desired. Here we present a concept for the introduction of the trifluoromethyl group into unprotected phenols by employing a biocatalyst (laccase), tBuOOH, and either the Langlois' reagent or Baran's zinc sulfinate. The method relies on the recombination of two radical species, namely, the phenol radical cation generated directly by the laccase and the CF
-radical. Various functional groups such as ketone, ester, aldehyde, ether and nitrile are tolerated. This laccase-catalysed trifluoromethylation proceeds under mild conditions and allows accessing trifluoromethyl-substituted phenols that were not available by classical methods.
A biocatalytic redox‐neutral reaction cascade was designed for the deracemisation of racemic mandelic acid to yield optically pure L‐phenylglycine employing three enzymes. The cascade consisted of ...three steps: a racemisation, an enantioselective oxidation and a stereoselective reductive amination. The enantioselective oxidation of D‐mandelic acid to the corresponding oxo acid was coupled with the stereoselective reductive amination of the latter; thus the oxidation as well as the reduction reactions were performed simultaneously. The formal hydrogen ed in the first step – the oxidation – was consumed in the reductive amination allowing a redox‐neutral cascade due to a cascade‐internal cofactor recycling. The enantiomers of the starting material were interconverted by a racemase (mandelate racemase) ensuring that in theory 100% of the starting material can be transformed. Using this set‐up racemic mandelic acid was transformed to optically pure L‐phenylglycine (ee >97%) at 94% conversion without the requirement of any additional redox reagents in stoichiometric amounts.
A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C–C bond formation catalyzed by berberine bridge enzyme ...(BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4–8 linear steps using either a Bischler–Napieralski cyclization or a C1–Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5–9 linear steps.
Imine reductases (IREDs) have recently become a primary focus of research in biocatalysis, complementing other classes of amine‐forming enzymes such as transaminases and amine dehydrogenases. ...Following in the footsteps of other research groups, we have established a set of IRED biocatalysts by sequence‐based in silico enzyme discovery. In this study, we present basic characterisation data for these novel IREDs and explore their activity and stereoselectivity using a panel of structurally diverse cyclic imines as substrates. Specific activities of >1 U/mg and excellent stereoselectivities (ee>99 %) were observed in many cases, and the enzymes proved surprisingly tolerant towards elevated substrate loadings. Co‐expression of the IREDs with an alcohol dehydrogenase for cofactor regeneration led to whole‐cell biocatalysts capable of efficiently reducing imines at 100 mM initial concentration with no need for the addition of extracellular nicotinamide cofactor. Preparative biotransformations on gram scale using these ‘designer cells’ afforded chiral amines in good yield and excellent optical purity.
All‐in‐one: A set of 14 imine reductases (IREDs) has been characterised and used for the reduction of a panel of structurally diverse imines. Co‐expression of the IREDs with an alcohol dehydrogenase afforded a convenient ‘all‐in‐one’ biocatalyst that reduced imines at the expense of 2‐propanol as co‐substrate and furnished chiral amines with excellent productivity and stereoselectivity.
Recent advances in bioeconomy allow a holistic view of existing and new process chains and enable novel production routines continuously advanced by academia and industry. All this progress benefits ...from a growing number of prediction tools that have found their way into the field. For example, automated genome annotations, tools for building model structures of proteins, and structural protein prediction methods such as AlphaFold2TM or RoseTTAFold have gained popularity in recent years. Recently, it has become apparent that more and more AI‐based tools are being developed and used for biocatalysis and biotechnology. This is an excellent opportunity for academia and industry to accelerate advancements in the field further. Biotechnology, as a rapidly growing interdisciplinary field, stands to benefit greatly from these developments.
A concept study on predictive biotechnology, which can be employed to map and optimize biological systems and processes through to technological implementation. A new tool for the resource‐saving (future) development of biotechnological processes.
Recent biocatalytic oxidation–reduction cascades Schrittwieser, Joerg H; Sattler, Johann; Resch, Verena ...
Current opinion in chemical biology,
April 2011, 2011-Apr, 2011-04-00, 20110401, Letnik:
15, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The combination of an oxidation and a reduction in a cascade allows performing transformations in a very economic and efficient fashion. The challenge is how to combine an oxidation with a reduction ...in one pot, either by running the two reactions simultaneously or in a stepwise fashion without isolation of intermediates. The broader availability of various redox enzymes nowadays has triggered the recent investigation of various oxidation–reduction cascades.
Research highlights ► Novel C–C bond formations from lyases, oxidoreductases and transferases reviewed. ► Highlights from lyases are the Stetter reaction, and the synthesis of N -heterocyclases and ...the first intermolecular Diels-Alderase. ► The highlight from oxidoreductases is the aerobic oxidative C–C coupling.
PDF
