One-Pot Bioisosteric Replacement of Alkyl Carboxylic Acids via Organic Photoredox Catalysis.

ABSTRACT: Drug development is often hindered by the pharmacokinetic and physicochemical limitations of lead compounds. Bioisosteric replacement is commonly employed to bolster drug viability; however, methods for accessing drug analogs are often synthetically inefficient. To address this challenge, we disclose strategies to access carboxylic acid bioisosteres via organic photoredox catalysis. A one-pot method enables the direct conversion of carboxylic acids to their most common bioisostere, tetrazoles. Additional functionalization to an amidoxime intermediate affords access to three other bioisosteres: oxathiadiazolones, oxadiazolones, and oxadiazole thiones. HPLC lipophilicity measurements of carboxylic acids and bioisostere derivatives illustrate the synthetic value of these methods for improving

SUBMITTER: Haney BA 

PROVIDER: S-EPMC12616624 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature