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Updated: Jun 17, 2025

High-Density DNA and RNA microarrays - Photolithographic Synthesis, Hybridization and Preparation of Large Nucleic Acid Libraries
Published on: August 12, 2019
Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library
Matteo Gasparetto1, Balázs Fődi1, Gellért Sipos1
1X-Chem Zrt., Záhony u. 7, DA Building, Graphisoft Park, Budapest, 1031, Hungary.
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.
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