Enzymkatalysierte späte Modifizierungen: Besser spät als nie

Romero, Elvira; Jones, Bethan S.; Hogg, Bethany N.; Casamajo, Arnau Rué; Hayes, Martin A.; Flitsch, Sabine L.; Turner, Nicholas J.; Schnepel, Christian

doi:10.1002/ange.202014931

Cited by 13 publications

(4 citation statements)

References 302 publications

(618 reference statements)

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“…The need of enantioselective methods for LSF could be met by future implementation of biocatalytic strategies, which are still absent from the toolbox of pyridine derivatization. Nonetheless, recent development augurs well for the use of enzymes in late‐stage functionalization of drugs and natural products [110] …”

Section: Discussionmentioning

confidence: 99%

Late‐Stage Functionalisation of Pyridine‐Containing Bioactive Molecules: Recent Strategies and Perspectives

et al. 2023

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Late-Stage Functionalisation (LSF) is an innovative technique that has been successfully applied to the CÀ H diversification of pharmaceuticals. However, LSF of the pyridine ring in drug-like molecules is often unselective. As a result, a mixture of structurally related products is obtained, thus making the purification tedious and time-consuming. This review shines a light on recent strategies addressing the selectivity issue in the LSF of complex natural products or drugs containing the pyridine moiety. Specifically, we have reviewed the efforts reported both in academia and industries with the hope of providing a guide for the LSF of elaborated pyridines.

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Section: Discussionmentioning

confidence: 99%

Late‐Stage Functionalisation of Pyridine‐Containing Bioactive Molecules: Recent Strategies and Perspectives

et al. 2023

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“…Methylation is an important and common structural modification in organic molecules especially in medicinal chemistry where methods for the selective introduction of methylene groups are popular in drug late‐stage modifications [246] . Methyltransferases (MTs) are widespread in Nature and are found in a large variety of organisms across the different kingdoms [247] .…”

Section: Novel Approaches On Biocatalytic C−o Bond Formationmentioning

confidence: 99%

New Trends and Future Opportunities in the Enzymatic Formation of C−C, C−N, and C−O bonds

et al. 2021

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Organic chemistry provides society with fundamental products we use daily. Concerns about the impact that the chemical industry has over the environment is propelling major changes in the way we manufacture chemicals. Biocatalysis offers an alternative to other synthetic approaches as it employs enzymes, Nature's catalysts, to carry out chemical transformations. Enzymes are biodegradable, come from renewable sources, operate under mild reaction conditions, and display high selectivities in the processes they catalyse. As a highly multidisciplinary field, biocatalysis benefits from advances in different areas, and developments in the fields of molecular biology, bioinformatics, and chemical engineering have accelerated the extension of the range of available transformations (E. L. Bell et al., Nat. Rev. Meth. Prim. 2021, 1, 1-21). Recently, we surveyed advances in the expansion of the scope of biocatalysis via enzyme discovery and protein engineering (J. R. Marshall et al., Tetrahedron 2021, 82, 131926). Herein, we focus on novel enzymes currently available to the broad synthetic community for the construction of new CÀ C, CÀ N and CÀ O bonds, with the purpose of providing the non-specialist with new and alternative tools for chiral and sustainable chemical synthesis.

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“…Generally, late‐stage functionalisation must proceed regio‐ and chemoselectively on highly functionalised peptides without the necessity of protecting or directing groups [7] . It is hence not surprising that biocatalysts harbouring an inherent bioorthogonality, high specificity, and compatibility with aqueous solution, are excellent tools for late‐stage modification that receive increasing attention [8] . Several enzymatic reactions, e. g., transpeptidation using sortase, template‐driven ligations or C α ‐formylglycine formation, are being used to obtain peptide conjugates [9–16] .…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Late‐Stage Halogenation of Peptides

et al. 2022

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The late‐stage site‐selective derivatisation of peptides has many potential applications in structure‐activity relationship studies and postsynthetic modification or conjugation of bioactive compounds. The development of orthogonal methods for C−H functionalisation is crucial for such peptide derivatisation. Among them, biocatalytic methods are increasingly attracting attention. Tryptophan halogenases emerged as valuable catalysts to functionalise tryptophan (Trp), while direct enzyme‐catalysed halogenation of synthetic peptides is yet unprecedented. Here, it is reported that the Trp 6‐halogenase Thal accepts a wide range of amides and peptides containing a Trp moiety. Increasing the sequence length and reaction optimisation made bromination of pentapeptides feasible with good turnovers and a broad sequence scope, while regioselectivity turned out to be sequence dependent. Comparison of X‐ray single crystal structures of Thal in complex with d‐Trp and a dipeptide revealed a significantly altered binding mode for the peptide. The viability of this bioorthogonal approach was exemplified by halogenation of a cyclic RGD peptide.

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Enzymkatalysierte späte Modifizierungen: Besser spät als nie

Cited by 13 publications

References 302 publications

Late‐Stage Functionalisation of Pyridine‐Containing Bioactive Molecules: Recent Strategies and Perspectives

Late‐Stage Functionalisation of Pyridine‐Containing Bioactive Molecules: Recent Strategies and Perspectives

New Trends and Future Opportunities in the Enzymatic Formation of C−C, C−N, and C−O bonds

Enzymatic Late‐Stage Halogenation of Peptides

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