Modular Combination of Enzymatic Halogenation of Tryptophan with Suzuki–Miyaura Cross‐Coupling Reactions

Frese, Marcel; Schnepel, Christian; Minges, Hannah; Voß, Hauke; Feiner, Rebecca C; Sewald, Norbert

doi:10.1002/cctc.201600317

Cited by 62 publications

(97 citation statements)

References 36 publications

(36 reference statements)

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“…[264][265][266] This has been realised to some extent by using the heterogeneous CLEAs of the flavin-dependent halogenases (Figure 26). 243,267 As the heterogeneous biocatalyst is easily removed from the reaction, compartmentalisation of biocatalysts and chemocatalysts can be achieved by filtration. 243,267 Methods where such intermediary processing is not required have also been reported.…”

Section: Integration Of Fl-hal With Transition-metal Catalysismentioning

confidence: 99%

Development of Halogenase Enzymes for Use in Synthesis

Latham

Brandenburger

Shepherd³

et al. 2017

Chem. Rev.

269

244

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Nature has evolved halogenase enzymes to regioselectively halogenate a diverse range of biosynthetic precursors, with the halogens introduced often having a profound effect on the biological activity of the resulting natural products. Synthetic endeavours to create non-natural bioactive small molecules for pharmaceutical and agrochemical applications have also arrived at a similar conclusion -halogens can dramatically improve the properties of organic molecules for selective modulation of biological targets in vivo. Consequently a high proportion of pharmaceuticals and agrochemicals on the market today possess halogens. Halogenated organic compounds are also common intermediates in synthesis and are particularly valuable in metal catalyzed cross-coupling reactions.Despite the potential utility of organohalogens, traditional non-enzymatic halogenation chemistry utilizes deleterious reagents and often lacks regiocontrol. Reliable, facile and cleaner methods for the regioselective halogenation of organic compounds are therefore essential in the development of economical and environmentally-friendly industrial processes. A potential avenue towards such methods is the use of halogenase enzymes, responsible for the biosynthesis of halogenated natural products, as biocatalysts. This review will discuss the advances towards this goal thus far, in addition to untapped potential sources of such biocatalysts and how further development of the enzymes may be focused in order to achieve the goal of industrial scale biohalogenation.

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Section: Integration Of Fl-hal With Transition-metal Catalysismentioning

confidence: 99%

Development of Halogenase Enzymes for Use in Synthesis

Latham

Brandenburger

Shepherd³

et al. 2017

Chem. Rev.

269

244

View full text Add to dashboard Cite

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“…Thus, it is not surprising to find in the literature several examples that reported the combination of metal-catalyzed C-C coupling reactions in aqueous media with different biotransformations. In this sense, this section covers the combination of: (i) Pd-catalyzed Suzuki coupling with bioreductions [100], bioaminations [101] or enzymatic halogenations [102,103]; and (ii) Pd-catalyzed Heck reaction and bioreduction [104]. Furthermore, and in the final part of this section, we review the combination of indium-mediated Barbier-type coupling [105] or Zn-catalyzed aldol reactions [106] with enzymatic oxidations or bioreductions, respectively.…”

Section: Combination Of Metal-catalyzed C-c Coupling Reactions With Ementioning

confidence: 99%

“…Finally, not only bioreductions [100] or bioaminations [101], but also enzymatic halogenations [102,103] have been efficiently coupled with Pd-catalyzed Suzuki reactions. In this sense, Sewald and co-workers [102] were the first to report the combination of the biocatalyzed halogenation of Ltryptophan with the subsequent Pd-catalyzed Suzuki cross-coupling reaction for the chemoenzymatic synthesis of different aryl-substituted tryptophans (Scheme 22). Thus, firstly, the regioselective bromination in the 5-, 6-or 7-position of the indole molecule of tryptophan was studied by employing Trp 5-halogenase PyrH, Trp 6-halogenase Thal or Trp 7-halogenase Rebh [112], respectively.…”

Section: Combination Of Metal-catalyzed C-c Coupling Reactions With Ementioning

confidence: 99%

“…Finally, and after this Boc-protection step, it was possible to perform the desired Pd-catalyzed Suzuki reaction by employing the complex [Pd(CH 3 CN) 2 Cl 2 ] as the catalyst (10 mol%) with the aid of microwave irradiation at 120 • C for 20 min (Scheme 21). Finally, not only bioreductions [100] or bioaminations [101], but also enzymatic halogenations [102,103] have been efficiently coupled with Pd-catalyzed Suzuki reactions. In this sense, Sewald and co-workers [102] were the first to report the combination of the biocatalyzed halogenation of Ltryptophan with the subsequent Pd-catalyzed Suzuki cross-coupling reaction for the chemoenzymatic synthesis of different aryl-substituted tryptophans (Scheme 22).…”

Section: Combination Of Metal-catalyzed C-c Coupling Reactions With Ementioning

confidence: 99%

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One-Pot Combination of Metal- and Bio-Catalysis in Water for the Synthesis of Chiral Molecules

2018

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During the last decade, the combination of different metal-and bio-catalyzed organic reactions in aqueous media has permitted the flourishing of a variety of one-pot asymmetric multi-catalytic reactions devoted to the construction of enantiopure and high added-value chemicals under mild reaction conditions (usually room temperature) and in the presence of air. Herein, a comprehensive account of the state-of-the-art in the development of catalytic networks by combining metallic and biological catalysts in aqueous media (the natural environment of enzymes) is presented. Among others, the combination of metal-catalyzed isomerizations, cycloadditions, hydrations, olefin metathesis, oxidations, C-C cross-coupling and hydrogenation reactions, with several biocatalyzed transformations of organic groups (enzymatic reduction, epoxidation, halogenation or ester hydrolysis), are discussed.

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“…The synthesis of 7-vinyltryptophan 29 with potassium vinyltrifluoroborate and PdCl 2 (dppf), starting from 7-iodotryptophan 28 in mixed aqueous conditions ( Figure 6B), broadened the scope of halotryptophan derivatization, along with the derivatization of unprotected bromotryptophan and bromotryptophan-containing dipeptides [97]. Recently, Frese et al combined a biocatalytic and regioselective tryptophan halogenation and Suzuki-Miyaura cross-coupling in a multi-step one-pot reaction [98]. The benign halogenation is performed via immobilized tryptophan 5-, 6-, or 7-halogenases using NaBr as a halogen source, followed by biocatalyst removal and subsequent Suzuki-Miyaura reaction.…”

Section: Access To and Derivatization Of (Pseudo)halogenated Aromaticmentioning

confidence: 99%

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

et al. 2017

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Abstract:The (site-selective) derivatization of amino acids and peptides represents an attractive field with potential applications in the establishment of structure-activity relationships and labeling of bioactive compounds. In this respect, bioorthogonal cross-coupling reactions provide valuable means for ready access to peptide analogues with diversified structure and function. Due to the complex and chiral nature of peptides, mild reaction conditions are preferred; hence, a suitable cross-coupling reaction is required for the chemical modification of these challenging substrates. The Suzuki reaction, involving organoboron species, is appropriate given the stability and environmentally benign nature of these reactants and their amenability to be applied in (partial) aqueous reaction conditions, an expected requirement upon the derivatization of peptides. Concerning the halogenated reaction partner, residues bearing halogen moieties can either be introduced directly as halogenated amino acids during solid-phase peptide synthesis (SPPS) or genetically encoded into larger proteins. A reversed approach building in boron in the peptidic backbone is also possible. Furthermore, based on this complementarity, cyclic peptides can be prepared by halogenation, and borylation of two amino acid side chains present within the same peptidic substrate. Here, the Suzuki-Miyaura reaction is a tool to induce the desired cyclization. In this review, we discuss diverse amino acid and peptide-based applications explored by means of this extremely versatile cross-coupling reaction. With the advent of peptide-based drugs, versatile bioorthogonal conversions on these substrates have become highly valuable.

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Modular Combination of Enzymatic Halogenation of Tryptophan with Suzuki–Miyaura Cross‐Coupling Reactions

Cited by 62 publications

References 36 publications

Development of Halogenase Enzymes for Use in Synthesis

Development of Halogenase Enzymes for Use in Synthesis

One-Pot Combination of Metal- and Bio-Catalysis in Water for the Synthesis of Chiral Molecules

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

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