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. 2021 Aug 20;25(8):1966-1973.
doi: 10.1021/acs.oprd.1c00208. Epub 2021 Jul 26.

Synthesis of Enantiopure Unnatural Amino Acids by Metallaphotoredox Catalysis

Tomer M Faraggi  1 , Caroline Rouget-Virbel  1 , Juan A Rincón  2 , Mario Barberis  2 , Carlos Mateos  2 , Susana García-Cerrada  2 , Javier Agejas  2 , Oscar de Frutos  2 , David W C MacMillan  1
Affiliations

Synthesis of Enantiopure Unnatural Amino Acids by Metallaphotoredox Catalysis

Tomer M Faraggi et al. Org Process Res Dev. .

Abstract

We describe herein a two-step process for the conversion of serine to a wide array of optically pure unnatural amino acids. This method utilizes a photocatalytic cross-electrophile coupling between a bromoalkyl intermediate and a diverse set of aryl halides to produce artificial analogues of phenylalanine, tryptophan, and histidine. The reaction is tolerant of a broad range of functionalities and can be leveraged toward the scalable synthesis of valuable pharmaceutical scaffolds via flow technology.

Keywords: flow chemistry; heterocycles; nickel catalysis; photoredox catalysis; unnatural amino acids.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Applications and synthesis of unnatural amino acids.
Scheme 1.
Scheme 1.
Proposed Mechanism for Cross-Electrophile Coupling
Scheme 2.
Scheme 2.
Scope of Naturally Derived Amino Acid Bromides
See this image and copyright information in PMC

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