Radical-Based Synthesis and Modification of Amino Acids
The use of chiral auxiliaries on the N-substituent of the imine allows for the formation of enantiopure α-AAs through diastereoselective radical additions. The most common auxiliary employed in these processes is the mesitylsulfinyl group, as its large steric demand allows for high levels of diastereocontrol during the key radical-addition step.
Dehydroalanine modification sees the light: a photochemical …
2022年7月1日 · In particular, the past 5 years have witnessed impressive progress on visible-light-driven radical conjugate addition (RCA) of dehydroalanine (Dha) and its application to site-selective functionalization of peptides or proteins, which remarkably advanced the scope of unnatural amino acid (UAA) synthesis as well as state-of-the-art ...
Nickel-Catalyzed Radical Mechanisms: Informing Cross-Coupling …
2023年11月30日 · Radical addition to dehydroalanine (Dha) provides a versatile and modular approach for synthesizing noncanonical peptide analogues, which are crucial for drug discovery. Previous studies on radical addition to the Dha residue of peptides and proteins have demonstrated excellent functional group compatibility.
Synthesis of modified proteins via functionalization of dehydroalanine …
2018年10月1日 · Dha in proteins is easily and flexibly accessible under mild conditions. Dha reactivity is used in β,γ-C–S/Se/N/C bond-formation and allows ‘zero scar’ protein mutagenesis. Chemical mutagenesis allows functional study of PTMs in nucleosome, kinome, proteasome. Precise, unnatural mutagenesis allows dissection of enzyme mechanism.
Aminoalkyl Radicals as Powerful Intermediates for the Synthesis of ...
2018年8月30日 · A robust method for the direct addition of unactivated tertiary amines to dehydroalanine (Dha) derivatives has been developed. This method, which is driven by a photoredox catalyst and light, operates through a C–H functionalization mechanism, where α-amino radical formation triggers highly chemoselective radical conjugate addition.
Late-Stage Modification of Oligopeptides by Nickel-Catalyzed ...
2022年9月29日 · Radical addition to dehydroalanine (Dha) represents an appealing, modular strategy to access non-canonical peptide analogues for drug discovery. Prior studies on radical addition to the Dha residue of peptides and proteins have demonstrated outstanding functional group compatibility, but the lack of stereoselectivity has limited the synthetic ...
Mechanism of Radical S-Adenosyl-l-methionine Adenosylation: Radical …
2022年3月3日 · We show that PFL-AE catalyzes the adenosylation of this Dha peptide (Dha-pep). Upon freeze-quench trapping, the reaction of reduced PFL-AE with SAM and Dha-pep gives the central RS paramagnetic organometallic intermediate Ω.
Light-driven post-translational installation of reactive ... - Nature
2020年9月23日 · In situ-generated BACED reagents release less stable alkyl radicals that, when used in higher abundance (100–2,000 equiv.), react selectively with the SOMOphile dehydroalanine (Dha) to install...
Light-initiated 1,3-dipolar cycloaddition between dehydroalanines …
2023年6月2日 · Here, we report a photoinitiated 1,3-dipolar cycloaddition reaction between Dha and 2,5-diaryl tetrazoles. Under low-power UV lamp irradiation, this reaction is completed within minutes without catalysis, resulting in a fluorescent pyrazoline-modified peptide or protein with excellent chemoselectivity for Dha residues.
Poly-Dha Sequences as Pro-polypeptides: An Original Mechanistic ...
2024年10月7日 · We test an original mechanistic postulate wherein a single peptide made entirely of dehydroalanine (Dha) residues can give rise to regio- and stereodefined peptides by iterative conjugate addition of one- or two-electron nucleophiles.
跳至内容