The transmembrane protein butyrophilin functions as an intracellular receptor for small phosphorus-containing compounds and when ligand bound it stimulates proliferation of γδ T cells. Because the most potent natural ligand, (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate is too unstable metabolically for potential clinical use, we have explored the preparation and biological activity of various phosphonate analogues. Our studies have uncovered potent prodrugs, including mixed acyloxy aryl esters (e.g. 1) and aryl phosphonamidates (e.g. 2), but in all previous cases the compounds were racemic. We now present the preparation of some nonracemic aryl phosphonamidates (e.g. 3 and 4), along with our initial studies of their biological activity.

Nonracemic prodrugs of a butyrophilin ligand

2019 Spring National Meeting

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