New Paper - On-DNA Hydrogenolysis and Hydrogenation

Angew. Chem. Int. Ed. 2022, 61, e202111927

https://doi.org/10.1002/anie.202111927

https://onlinelibrary.wiley.com/doi/10.1002/                                                                                 anie.202111927

Harriet A. Stanway-Gordon, Jessica S. Graham and Michael J. Waring*

DNA-encoded libraries (DELs) are an increasingly popular approach to finding small molecule ligands for proteins. Many DEL synthesis protocols hinge on sequential additions of monomers using split-pool combinatorial methods.  Therefore, compatible protecting group strategies or removal of less desirable functionality are highly desirable. Hydrogenation/hydrogenolysis procedures would achieve this but have previously not been amenable to DEL chemistry. 

This work, carried out by chemistry PhD students, Harriet Stanway-Gordon and Jessica Graham, demonstrates a highly efficient method of hydrogenolysis and hydrogenation of DNA-conjugated substrates using Pd/C, HCONH₄ and the micelle-forming surfactant, TPGS-750-M.

Application to multicycle synthesis of an encoded compound was fully compatible with DNA-amplification and sequencing, demonstrating its applicability to DEL synthesis. This methodology will enable synthetic DEL sequences using orthogonal protecting groups and provides a valuable addition to the current range of transformations available in DEL synthesis.

Last modified: Mon, 19 Dec 2022 17:18:57 GMT