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Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications.

ABSTRACT: Amino acids are vital motifs in the domain of biochemistry, serving as the foundational unit for peptides and proteins, while also holding a crucial function in many biological processes. Due to their bifunctional character, they have been also used for combinatorial chemistry purposes, such as the preparation of DNA-encoded chemical libraries. We developed a practical synthesis for α-heteroaryl-α-amino acids starting from an array of small heteroaromatic halides. The reaction sequence utilizes a photochemically enhanced Negishi cross-coupling as a key step, followed by oximation and reduction. The prepared amino esters were validated for on-DNA reactivity via a reverse amidation-hydrolysis-reverse amidation protocol.

SUBMITTER: Gasparetto M

PROVIDER: S-EPMC11318629 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications.

Gasparetto Matteo M Fődi Balázs B Sipos Gellért G

Beilstein journal of organic chemistry 20240808

Amino acids are vital motifs in the domain of biochemistry, serving as the foundational unit for peptides and proteins, while also holding a crucial function in many biological processes. Due to their bifunctional character, they have been also used for combinatorial chemistry purposes, such as the preparation of DNA-encoded chemical libraries. We developed a practical synthesis for α-heteroaryl-α-amino acids starting from an array of small heteroaromatic halides. The reaction sequence utilizes ...[more]

PMID: 39135657

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