Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors.

Basic Information

ID: ALA4842394

Journal: ACS Med Chem Lett

Title: Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors.

Authors: Li D, Zhang H, Lyons TW, Lu M, Achab A, Pu Q, Childers M, Mitcheltree MJ, Wang J, Martinot TA, McMinn SE, Sloman DL, Palani A, Beard A, Nogle L, Gathiaka S, Saurí J, Kim HY, Adpressa D, Spacciapoli P, Miller JR, Palte RL, Lesburg CA, Cumming J, Fischer C.

Abstract: Comprehensive synthetic strategies afforded a diverse set of structurally unique bicyclic proline-containing arginase inhibitors with a high degree of three-dimensionality. The analogs that favored the Cγ-exo conformation of the proline improved the arginase potency over the initial lead. The novel synthetic strategies reported here not only enable access to previously unknown stereochemically complex proline derivatives but also provide a foundation for the future synthesis of bicyclic proline analogs, which incorporate inherent three-dimensional character into building blocks, medicine, and catalysts and could have a profound impact on the conformation of proline-containing peptides and macrocycles.

CiteXplore: 34795856

DOI: 10.1021/acsmedchemlett.1c00258

Patent ID: