Diversified strategy for the synthesis of DNA-encoded oxindole libraries

Abstract

Constructing DNA-encoded oxindole libraries by a diversified strategy.

Highly efficient on-DNA amide couplings promoted by micelle forming surfactants for the synthesis of DNA encoded libraries

“…Coupling of glycine ethyl ester, aniline and 2-aminothiazole with 2 using HATU 27 showed a clear improvement in reactivity, with formation of the desired amides in 57%, 15% and 45% respectively. In contrast, use of EDC/HOAt 28 or DMT-MM, 29 which are preferred reagents for amide couplings on-DNA, 4,19,30 resulted in no conversion. With HATU, conversion could be improved by heating at 40 C for glycine ethyl ester and 2-aminothiazole (90% conversion in both cases) but led to a slight reduction for aniline.…”

Functionalization of DNA-Tagged Alkenes with Diazo Compounds via Photocatalysis

“…13 In light of the importance of this scaffold, we turned our attention to the search for a facile way to form cyclopropanes in DEL synthesis. 14 To our delight, simple replacement of the Hantzsch ester and 4-methylbenzenethiol with I 2 11d gave the corresponding cyclopropane 5a in 72% yield. 15 Subsequently, the scope of the on-DNA cyclopropanation was examined, as shown in Table 3.…”

“…Cyclopropane has emerged as an important skeleton in drug design that can significantly improve the druggability of specific molecules . In light of the importance of this scaffold, we turned our attention to the search for a facile way to form cyclopropanes in DEL synthesis . To our delight, simple replacement of the Hantzsch ester and 4-methylbenzenethiol with I 2 gave the corresponding cyclopropane 5a in 72% yield .…”

Opportunities for Expanding Encoded Chemical Diversification and Improving Hit Enrichment in mRNA‐Displayed Peptide Libraries

“…Such an aldehyde can in turn be decorated with new moieties by reductive alkylations and oxime‐ [87] or hydrazine‐ligations. [88] Other examples of aldehyde‐based diversification from DNA‐compatible chemistry that offer significant promise from a drug discovery perspective include a report on construction of a large variety of heterocycles, [60] including newly developed protocols for the preparation of isoquinolones, [89] oxindoles [90] and thiazole‐fused dihydropyrans; [91] and a number of isocyanide‐based multicomponent reactions. [92] Note that a solid‐support strategy is used for these reactions to enhance DNA‐stability, which has also been deployed in mRNA display‐based methods (mentioned in section 4.1 below).…”