Synthesis of Diverse Glycosyl Bicyclo[1.1.1]pentanes Enabled by Electrochemical Functionalization of [1.1.1]Propellane.

ABSTRACT: Over the past decade, bicyclo[1.1.1]pentanes (BCPs) have emerged as valuable bioisosteres of aromatic rings, offering unique three-dimensional architectures for medicinal chemistry. Meanwhile, glycosyl derivatives play a pivotal role in chemical biology and drug discovery due to their widespread presence in biologically active molecules; however, the potential of bicyclo[1.1.1]pentanes (BCPs) as versatile scaffolds in glycoscience remains largely unexplored. Herein, we report an electrochemistry strategy for the synthesis of BCP-glycosides via the functionalization of [1.1.1]propellane. By leveraging an electrochemical halogen-atom transfer (e-XAT) process, we achieved a one-step, three-component reaction of glycosyl bromides, [1.1.1]propellane, and radical acceptors under mild conditions, enabling the construction of glycosyl BCP-iodides, glycosyl BCP-H, and glycosyl BCP-pinacolboronic esters (Bpins) with exceptional functional group tolerance and scalability. Mechanistic studies suggested that the electrochemical process facilitated the generation of radical intermediates, which underwent selective addition to [1.1.1]propellane, followed by trapping with radical acceptors. This study establishes a versatile platform for late-stage functionalization and streamlined access to privileged scaffolds in drug discovery and chemical biology.

SUBMITTER: Liu J 

PROVIDER: S-EPMC12465002 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature