Library design has been an important part of DNA-encoded library technology (DEL). The efficiency of the design depends on chemical building blocks (BBs) utilized to assemble the library. Therefore, availability of novel diverse BBs with high reactivity and specific structural features, i.e. small size, not lipophilic, and 3D shape, is of importance to succeed in producing high-quality DELs. This is especially critical while selecting core BBs with two or three orthogonal functions complied with DEL chemistry. Indeed, these polyfunctional BBs have been underrepresented on the market thus requiring approaches to make them synthetically and economically accessible.<br/>For more than 25 years, we have been working on the synthesis of BBs, intermediates, and screening compound libraries accumulating the knowledge of manual and parallel synthetic chemistry. We applied this knowledge to the inventory of BB’s that allowed to generate a set of polyfunctional BBs on a multimilligram-to-gram scale readily accessed via validated synthetic approaches, i.e., alkylation, arylation, protective group addition. Novelty, exclusivity and favorable physicochemical profiles of starting reagents support the production of high-quality core BBs.

Approaches to synthetically feasible polyfunctional building blocks

255th National Meeting (2018)

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