biostudies-literatureMeanwell MGouvernement du Canada | Natural Sciences and Engineering Research Council of CanadaGouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)96https://www.ebi.ac.uk/biostudies/studies/S-EPMC9814271biostudies-literatureUnknown4(1)Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups. Using density functional theory calculations, we demonstrate both steric and electrostatic interactions play key diastereodiscriminating roles in the dynamic kinetic resolution. The utility of tCommunications chemistryDiversity-oriented synthesis of glycomimetics.PMC98142712019-06368Rowshanpour RDudding TRen WFehr GMeanwell MAdluri BBergeron-Brlek MBritton RFoy HLehmann JCampeau LCRose VAdamson CSilverman SMChalla VRfalseDiversity-oriented synthesis of glycomimetics.Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups. Using density functional theory calculations, we demonstrate both steric and electrostatic interactions play key diastereodiscriminating roles in the dynamic kinetic resolution. The utility of t2021-01-01T00:00:00Z2021 Jun2025-04-21T23:17:36.38Z2025-04-05T19:05:48.968ZS-EPMC98142713669754810.1038/s42004-021-00520-3