The Potential of Micellar Media in the Synthesis of DNA‐Encoded Libraries

Abstract

DNA-encoded library (DEL) technology has become widely used in drug discovery research. The construction of DELs requires robust organic transformations that proceed in aqueous media under mild conditions. Unfortunately, the application of water as reaction medium for organic synthesis is not evident due to the generally limited solubility of organic reagents. However, the use of surfactants can offer a solution to this issue. Oil-in-water microemulsions formed by surfactant micelles are able to localize hydrophobic reagents inside them, resulting in high local concentrations of the organic substances in an otherwise poorly solvated environment. This review provides a conceptual and critical summary of micellar synthesis possibilities that are well suited to DEL synthesis. Existing examples of micellar DEL approaches, together with a selection of micellar organic transformations fundamentally suitable for DEL are discussed.

DNA-encoded librariesvialate-stage functionalization strategies: a review

“…[67][68][69][70] Micellar catalysis involves the formation of micelles effectively around the organic part of the DNA-conjugated moiety, focusing on the desired region of the reacting component, while the DNA part would remain in the aqueous phase without any damage. 71,72 Thus, the use of micelles could be helpful in the diversification of the DEL synthesis, and this section enlists the various developments that have taken place in the past several years.…”

On drug discovery against infectious diseases and academic medicinal chemistry contributions

“…These turned out to also be effective against SARS-CoV-2 main protease [243] and thus provided the key structure-based data for two distinct fruitful hit to lead programs against this virus [78,81,82]. The current generation of DNA-encoded libraries, a technique which stemmed from an academic [244,245] thought experiment and was quickly adopted by industrials [246,247], is also a noteworthy incentive for innovation in organic chemistry [248][249][250][251][252]. However, and still on COVID-19, the DNA-encoded chemical library approach which led to yet another aldehyde-bearing compound effective against SARS-Cov-2 main protease remains to be judged as relevant [253].…”

Micelle‐Mediated Sonogashira Coupling for DNA‐Encoded Library Synthesis

“…We, [11–14] and others, [15] have reported the use of micelle‐forming surfactants to promote on‐DNA reactions that offers a versatile means of carrying out organic reactions in an aqueous medium. The reactions that we have reported proceed with excellent conversion, tolerate a broad substrate scope and use the commercially available surfactant TPGS‐750‐M, providing operationally simple procedures [16] …”

“…The reactions that we have reported proceed with excellent conversion, tolerate a broad substrate scope and use the commercially available surfactant TPGS-750-M, providing operationally simple procedures. [16] Given the significance of the Sonogashira reaction in medicinal chemistry, several groups have developed on-DNA Sonogashira couplings. [17][18][19] In one pioneering study, the coupling between aryl fluorosulfonates and alkynes was reported with moderate to high conversion.…”