0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login to access the full content or check if you have access via
2.9 On-DNA Functional-Group Transformations

DOI: 10.1055/sos-SD-241-00134

Simmons, N.; Chheda, P.; Schuman, D.Science of Synthesis: DNA-Encoded Libraries, (20241363.

General Introduction

Although the implementation of DNA-encoded library (DEL) technologies through the DEL design, production, screening, and data-analysis phases may vary greatly between organizations, in general, the strategy for accessing diverse DEL chemical matter centers around a few approaches. These include the diversity inherent in coupling large building-block sets with multiple cycles of chemistry, which may also bring chemotypes that cannot be formed through on-DNA chemistries; the use of designed multifunctional core sets with subsequent decoration by building blocks; or the crafting of bespoke chemistries to access specific chemotypes, albeit often at the expense of reagent availability and scope.[‌1‌‌3‌] Within these approaches, the predominant technique is to rely on functional groups already installed within the reactants for product formation. This is attractive, as it simplifies build complexity and improves DEL product purity by limiting the accumulation of on-DNA-generated side products that are often impractical or impossible to remove and which can complicate later DEL resynthesis campaigns.[‌4‌,‌5‌] However, the incorporation of additional on-DNA functional-group transformations, broadly defined here as an alteration of an on-DNA functional group without incorporation of a new diversity element, can also be an avenue to enhance overall DEL chemical matter diversity. The application of on-DNA functional-group transformations includes: the use of protecting groups to ensure regioselectivity, orthogonality, or better coupling efficiency; the in situ preparation of commercially rare or unstable intermediates for multistep protocols; the extension of valuable in-stock cores or building blocks to new DEL synthetic pathways through functional-group interconversion; the installation of a desired functional group within the final molecule as part of the planned diversity or as a formal encoding of an expected byproduct; and, in some cases, additionally as a handle that modulates other reactivity within the planned DEL synthetic sequence.

Me eeee eeeeeee, ee eeeeeee (8) eeeeeeeeeeeeee eee eeeeeeeeeeeeee ee ee-MMM eeeeeeeeee-eeeee eeeeeeeeeeeeeee; (8) eeeeeeee eeeeeee ee eee eeeeeeeeee eeeee eeeeee eeee eeee MMM eeeeeeeeee eee eeeee, eeeeee eeeeeeee eeee eeeeeee eeeeeeeeeee, eee eeeeeeeee eeeeeeeeeeee eeeeeeeee; (8) ee eeeeeee ee eeeeee eeeeeeeeee. Meeeeeee eeeeeeeee eee eeee eeeeeeeee eeeeeee eee eee eeee eeee eeeeee eee eeeeeee eee eeeee. Me ee eee eeeeee ee eeee eeeeeee ee eeee eee eeeeeeeeee ee eeeeeeeeee-eeeee-eeeeeeeeeeeeee eeeeeeeee eeee eeeeeeee ee eee eeeeeee MMM eeeeeeeee; eeeeee eeeeeeeeeee eeeee, ee eeeee eeeeeee eeeeeeeeeeee eeeeeeeeee ee eeeeeeee ee eeeeeeeeee, eee eee ee eeeeeee ee eee eee eeee eee eeeeeeeeeeee eeeeeeee eeeeee ee eeeeee. Mee eeeeeeeeeeeee ee eeeeeeee eeeeeeeeee eeeeeee eeeee-eeeee (e.e., ee-eeee ee eeeeeeeeee-eeee eeeee) eee eeeeeee eeeeeeee-eeeee MMM eeeeeeeeeee eee ee eeeeee eeeeeeeee eee eeeeee eee ee eeeeeee ee ee eeeeeeeeeeeeeee.

Meeeee eeeeeeeee eee MMM eeeeeeeeee, eeeeeeeee e eeeeeeeeeee eeeeee ee eeee ee eeeee ee eeeeeeeee eeeeeeeee, eeeeeeeeee MMM eeeeeeee eeeeeeeee eee eee eeeeeeee eeeeeeeeeee, eee eeeeeeeeee eeeeeeee eeeeee ee eeeeeeeee eee eeeeee eeeeeeee-eeeee eee eee eeeeeeeeee ee ee-MMM eeeee eeeeeeee eeeeeee.[‌8‌] Meee eeeeeeee eeeeeeee ee eeeeeeee eee eeeeeee eeeeee eee ee ee eeeeeeeee eeee ee eeeeee e eeee eeeeeeeeeeeee ee eeeeeeee eeeee eee eee eeeeeeeeeee. Meee ee eeeeeeeeeeee eeeeeeeee ee eee eeee ee ee-MMM eeeeeeeeee-eeeee eeeeeeeeeeeeeee eeee eee ee eeee ee eeeeee eeeeeeeeeeeee ee eee eeeeeeee eee eee eeeeeeee ee eeeeeeee eeeeee eee eeeeeeeee eeeeeeee. Meeeeeee ee eeeeeee eeeeeeeeee ee eeeeeee eeeee eeeeeee eeeeeeeee eeeeeeeeeee eeeeee e eeeee eeeeeeeeeeeee MMM eeeeeeeeee, eee eeeeeee-eeeeeee eeeeeeee ee eee eeeee eeeee ee MMM eeeeeeeeee eee eeeeee, ee eeeeeeee eeeeeeeeeee eee ee eeeeeeee eeeeeeeee ee eeee eeeeeeeeeeee. Meee eeeeeee eeee eeeeeeeee ee eee eeeeee eeeeee ee MMM eeeeeeeeee, eee eeee-ee-eeeeee (e/e) eeeeeeeeeeee eeee eeeeeeeeeeee eeeeee ee eeeeee MMM eeeeeeeee eee eeeeeeee eeee ee eeeeeeee eeee eeee eee ee eeee ee eeeeeeeeee eeeeeeee–eeeeeee eeeeeeeee-eeeeee eeeeee.[‌8‌] Me eee eeee ee eeeeeeeeee-eeeee eeeeeeeeeeeeeee ee eeeee eeeee ee e eeeeeeeee eeee ee eeee ee eeeeeeeee eeeeee eeeee MMM eeeeeeeee, eeeeeeeeee ee eeee eeeeeeee eeeeee eeeee eee ee eeee eeeee ee eeeeeeeeeee eee eeeeeee eeeeeeeeeee eee eeeeeeeeee eee ee eee ee-MMM eeeeeeeeeeeeee eeeeeeee ee eeeeeee eeeeeeeee.

Mee eeeeee ee ee-MMM eeeeeeeee eee eeee, eeeeeeeee ee eee eeeeee eee eeee ee eeeeeeee eeee. Mee eeeee-eeeee eeeeeeeeeee, eeee eeeee eeeeeeee eeeeeee, eeeeeeeeee, eee eeeeeeeeee eeeeeeee eeeee ee eeeeee eeeeeeee eeeeeeeeeee ee eeee eeeeeeeeeeee. Mee eeeeeeee-eeeee eeeeeeeeeee, eee MMM eee ee eeeeeeee eeeeeeee ee eeeeee e eeeeee ee eee eeeeeeee eeeeeee; eeeeeee, ee eeee eeeee, ee ee eeeeeeeee ee eeeee ee e eeeeeeeeeeee eeee. Meee eeeee eeeeeee eeeeeee eeeeeeeeeeeee ee eeeeeee eee MMM, eeee-eeeeeeeee eeeeeeeeeee eeeeeeeeee, ee eeeeeee eeeeeeeee ee eeeeeeeee eeeeeeeeeeee ee eeeeeeeeeeeeee eee eeeeeeee ee eee eeeeeeeeeee ee eeeeeee eeeeee ee eeeee eeeee eeeeee, MMMM eeeeeeeeeeee, ee eeeeeeeeeeee ee eeeee eeeeeeee eeee e eeeeeeeee.[‌8‌] Me ee eeeeeee eeeeeee eeee ee eeee, eeee eeeeeeee eee eeeeeeee eeeeeeeeee eeeee eeeeeeeeeeee eeeeeeeeee, eeeeeee eeeeeee eeeeeee ee eeeeeeeeeeee eeee eeeeeeeeeeee eeee, ee eeee eeeeeeeee eeeeee eeee eeee MMM eeeeeeee eeeeeeeee. Me eeee ee eee eeeeeeee eeeeeeeee, eeeeeeee eeeeeee ee eee eeeeee eeeeeeee eeee eee eeeeeeee; eeee, eeee ee eee eeeeeeeeee eeeeeee ee eee eeeeeeee, eeeeeeee eeeeee eeeee eeeeeeeeeeeee ee eeeeee eeee eeeeeeee ee MMM, eeeee eeeeeeeee eee eeeeeeeeee eeeee, eee eeeeeeee eeeeeeeeee eeeeeeee.

Meeeeeee eeeeeeeeee eeeeeee ee eeeeeeeeee-eeeee eeeeeeeeeeeeee eeeeeee eee eeeeeeee ee e eeeeeeeee eeeeeeee eeeee eee ee eeeeeeeee ee eeeeeeeeee eeeee ee ee e eeeeee eeeeeee. Me ee ee eeeeeeeee ee eee eeeeeeeeee eeee eeeee, ee eeeeeeee eeeeeee eeeeeee eeee eeeeeeee eeeeeeeeee eee eee eeeeeee ee eee eeeeeeeeeeeeeee ee eeeeeeeeee eeeeeeeeee. Meeeeeeeee, eeee-eeeeeeee eeeeeeeeeee eee eeeeeeeeeeeee eeee eeeeeeee, eeee eeeeeeeeeee ee eeee eee MMM eeeeee eee eeeeeee, eee eee ee eeeeeeeeeee ee eeeeeeee eeeeeeee ee eeeeeeee eeeeeeeeeeee eeeeeeee ee eee eeee. Meeeee eeeeeeeee eee ee eeeeee eeeeeeee eeeeee eee, eee eeeeee eeeeeeeeeeeeeee eee eeeeee eeee eeeeeeeeee eeeee eeeeeee eeee eeeeee eeeeeee ee eeeeee, eeeeeeeeee ee eeeeeee ee eeeeeeeee eeeeeee eeeeeeee eee eeee. Me eeeeeee, ee ee eeeeeeeee eeee eeeeeeee eeeeeeee ee eeeeeee, eeeee eeeeeeeeee-eeeee eeeeeeeeeeeeee eeeeeeeeee eeeeee ee eeeeeeeeee eeeeeeeee ee eeeeeeee eeeee eeeeeeeeee ee eeeeeeeeeeeeee eeeeeeee eeeeee, MMM eeeeee, eee eeeeeeeeeeee ee eeeeee eeeeeeee eee eeeeee ee eeeeeeee. Me eeeeeeee, eeeeeeeeeee ee eeeeeeee eeeeeeee eeeeeeee ee e eeeeee MMM eeeeeeeeee (e.e., eeeeeeeeeeee ee e eeeeeeee ee eee eeeeeee eeeeeee eeeeeeee eeeeee eeee eeee e eeeeeeeeee eeeee) eee eeee eee eeeeeeee eeeeeeeeeeee ee eeeeeeee-eeeeee MMM eeeeeeeee ee eee eeeee eeeeeeee, eeeeee eeee eeeeeee MMM eeeeee ee eeeeeeee eeeeee. Meeeeeee eeeeeeeeeee eee ee eeee eeeeeee eeeeeeeeeeee eeeeeeeeeeeeee ee eeeeee eeeeee ee eeeeeeee eeeee, eeeeeeeeee eee eeeeeeeee eee ee eeeeeeee ee e “eeïee” eeeeeeeeee ee eee eeeeeeee MMM.[‌8‌] Mee eeee eeeeeeeeeeee, e eeeeee eeeeeeeee eeee eee eeeeeeee Meeeeeee eeeeeeeeeeee ee eeeeeeeee, eee eeee MMMe eee eeeee eeeeeee eeeeee eeeeeeeeee eeeeeeeee eeeeeee.