A practical and scalable system for heteroaryl amino acid synthesis

Abstract

Here, we describe a highly-effective catalytic method for the synthesis of heteroarene-containing unnatural amino acids.

Synthesis of Unnatural α‐Amino Acid Derivatives via Light‐Mediated Radical Decarboxylative Processes

“…However, the application of these technologies for the synthesis of enantiopure UAA remains highly underexplored . For example, Jui and Gaunt have recently reported the use of photoredox catalysis in combination with Beckwith‐Karady alkene ( 1 ) for the synthesis of enantiopure UAA derivatives (Figure B).…”

“…Once the scope and limitations of the methodology were established, the deprotection and derivatization of the oxazolidinone core was carried out (Scheme ). When acidic conditions were used for the deprotection of 2 , free α‐amino acid 44 was obtained in 96% yield. The latter can be readily reacted with FmocCl or FmocOSu to afford the corresponding Fmoc protected α‐amino acid, which is a key species for the automated solid phase synthesis of peptides .…”

Photocatalytic Modification of Amino Acids, Peptides, and Proteins

“…[66] In 2017, Jiu andc o-workersr eported the possibility of activating pyridyl halides through ap hotoredox-induced SET and demonstrated the subsequenta ddition of these radicals pecies to DHA derivatives. [67] Optimized reaction conditions comprised the use of [Ir(ppy) 2 (dtbbpy)]PF 6 as ap hotocatalyst,a n excess of the Hantzsch ester as ar eductant,a nd as olvent mixture of DMSO/H 2 O. The developed protocol provede fficient for the preparation of aw ide range of b-heteroaryl a-amino acid derivatives (Scheme 21).…”

Versatile Ru‐Photoredox‐Catalyzed Functionalization of Dehydro‐Amino Acids and Peptides

“…Thus, pioneer work employing iridium(III) photoredox catalysis has been made in this field in the past few years. However, these methods are restricted to the Karady‐Beckwith alkene or, for the more valuable acyclic α,β‐dehydroamino acids, to the use of halopyridines, N ‐alkyl tertiary amines, potassium phenoxymethyl trifluoroborates and imines as radical precursors and/or coupling partners. Aiming at a more general and less costly method, we herein present a ruthenium(II) photoredox‐catalyzed functionalization of dehydroamino acids and peptides with a broad variety of alkyl radical precursors, which allows to easily introduce fluorinated and fatty acid‐derived chain groups, as well as carrying on late stage peptide functionalization (Scheme c).…”