Employing Photoredox Catalysis for DNA‐Encoded Chemistry: Decarboxylative Alkylation of α‐Amino Acids. (23rd August 2018)

• Record Type: Journal Article
• Authors: Kölmel, Dominik K.; Loach, Richard P.; Knauber, Thomas; Flanagan, Mark E.
• Is Part Of: ChemMedChem. Volume 13:Number 20(2018)
• Page Start: 2159
• Page End: 2165
• Publication Date: 2018-08-23
• Subjects: amino acids -- decarboxylative coupling -- DNA -- photoredox catalysis -- radical reactions; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201800492
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: A new procedure for the photoredox‐mediated conjugate addition of radicals that can be conveniently generated from α‐amino acids to DNA‐tagged Michael acceptors and styrenes is presented. This C(sp 3 )−C(sp 3 ) coupling tolerates a broad array of structurally diverse radical precursors, including all of the 20 proteinogenic amino acids. Importantly, this reaction proceeds under mild conditions and in DNA‐compatible aqueous media. Furthermore, the presented reaction conditions are compatible with DNA, making this reaction platform well suited for the construction of DNA‐encoded libraries. The scope and limitations of the chemistry are discussed herein along with proposals for how this methodology might be used to construct DNA‐encoded libraries. Abstract : DNA‐encoded chemistry in a new light : For the first time, photoredox catalysis is demonstrated to be amenable to the specific requirements of DNA‐encoded chemistry. The addition of various radicals to structurally diverse, DNA‐tagged radical acceptors was achieved by photoredox‐mediated oxidation of α‐amino acids. The described reaction proceeds under mild conditions in aqueous media and is compatible with DNA tags.