- Suzuki–Miyaura Cross-Coupling of Bromotryptophan Derivatives at Ambient Temperature
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Mild reaction conditions are highly desirable for bio-orthogonal side chain derivatizations of amino acids, peptides or proteins due to the sensitivity of these substrates. Transition metal catalysed cross-couplings such as Suzuki–Miyaura reactions are highly versatile, but usually require unfavourable reaction conditions, in particular, when applied with aryl bromides. Ligand-free solvent-stabilised Pd-nanoparticles represent an efficient and sustainable alternative to conventional phosphine-based catalysts, because the cross-coupling can be performed at considerably lower temperature. We report on the application of such a highly reactive heterogeneous catalyst for the Suzuki–Miyaura cross-coupling of brominated tryptophan derivatives. The solvent-stabilised Pd-nanoparticles are even more efficient than the literature-known ADHP-Pd precatalyst. Interestingly, the latter also leads to the formation of quasi-homogeneous Pd-nanoparticles as the catalytic species. One advantage of our approach is the compatibility with aqueous and aerobic conditions at near-ambient temperatures and short reaction times of only 2 h. The influence of different Nα-protecting groups, boronic acids as well as the impact of different amino acid side chains in bromotryptophan-containing peptides has been studied. Notably, a surprising acceleration of the catalysis was observed when palladium-coordinating side chains were present in proximal positions.
- Dachwitz, Steffen,Duwe, Dario H.,Wang, Yating Hong,Gru?, Hendrik,Hannappel, Yvonne,Hellweg, Thomas,Sewald, Norbert
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- Negishi Cross-Coupling Provides Alkylated Tryptophans and Tryptophan Regioisomers
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Mild transition-metal catalysed cross-couplings enable direct functionalisation of biocatalytically halogenated tryptophans with alkyl iodides, representing a new alternative for late-stage derivatisations of halogenated aromatic amino acids. Moreover, this strategy enables preparation of (homo)tryptophan regioisomers in a simple two-step synthesis using a Pd-catalysed Negishi cross coupling. This method provides access to non-canonical constitutional surrogates of tryptophan, ready for use in peptide synthesis.
- Dachwitz, Steffen,Scharkowski, Bjarne,Sewald, Norbert
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supporting information
p. 18043 - 18046
(2021/11/16)
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- Mild, Aqueous α-Arylation of Ketones: Towards New Diversification Tools for Halogenated Metabolites and Drug Molecules
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The palladium-catalysed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.
- Marelli, Enrico,Renault, Yohann,Sharma, Sunil V.,Nolan, Steven P.,Goss, Rebecca J. M.
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p. 3832 - 3836
(2017/03/27)
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- Total synthesis guided structure elucidation of (+)-psychotetramine
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Solving the puzzles: Total synthesis played a key role in the elucidation of the stereochemistry and verification of the constitution of the complex polymeric natural product psychotetramine. The route features three powerful assembly processes that enabl
- Foo, Klement,Newhouse, Timothy,Mori, Ikue,Takayama, Hiromitsu,Baran, Phil S.
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supporting information; experimental part
p. 2716 - 2719
(2011/06/09)
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- Synthesis of a TMC-95A Ketomethylene Analogue by Cyclization via Intramolecular Suzuki Coupling
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(Equation presented) A TMC-95A analogue extended at the C-terminus with NleΨ[COCH2]Gly-Ala-Ala-NH2 was synthesized via side-chain cyclization of the linear precursor by a Suzuki cross-coupling reaction in solution to analyze the effe
- Kaiser, Markus,Siciliano, Carlo,Assfalg-Machleidt, Irmgard,Groll, Michael,Milbradt, Alexander G.,Moroder, Luis
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p. 3435 - 3437
(2007/10/03)
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