Spiroligomers, poly-heterocyclic macromolecules with predictable and programmable shapes and structures, are assembled by microwave-assisted Fmoc solid-phase synthesis. Novel non-proteinogenic quaternary α-amino acid building blocks featuring orthogonal Fmoc/tBu protecting groups allow rapid iterative couplings followed by global TFA-mediated cleavage/deprotection/diketopiperazine clousure. Combinations of monomers incorporating different functional groups and stereochemistry enable the construction of diverse conformationally rigid arrays with distinct geometry. The developed methodology together with computational tools, like CANDO, provides the access to constrained poly-heterocyclic scaffolds with discrete sizes and 3D-shapes. It opens up new opportunities for medicinal chemists, biochemists and molecular biologists to design ligands, capable of interacting with a variety of biological targets. Spiroligomers quickly gather pace in the development of metal and protein binding molecules, enzyme mimics, DNA-encoded libraries, membranes and sensors. The present study outlines the synthesis of spiroligomers displaying multiple boronic acid moieties and their prospective applications as saccharide sensors and potential drugs targeting the glycan processing pathway.

Microwave-assisted solid-phase synthesis of spiroligomers based on the Fmoc/tBu protecting group strategy

ACS Spring Meeting 2021

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