Synthesis of Oligomers of β‑l‑Arabinofuranosides of (4R)‑4-Hydroxy‑l‑proline Relevant to the Mugwort Pollen Allergen, Art v 1

An efficient, convergent solution phase synthesis of monomer, dimer, trimer and tetramer of the β-l-arabinofuranosylated hydroxyproline (β-l-Araf-Hyp) glycocluster is described. This motif constitutes the carbohydrate-specific epitope of Art v 1, the major allergen of mugwort pollen. While a single monomeric unit was proposed at the outset, poor yields for the seemingly trivial steps of end-capping to replace protecting groups with N-terminal acetamides and C-terminal methyl amides led to the introduction of N-terminal, central and C-terminal β-l-Araf-Hyp building blocks. Dimer 2 was obtained in 60% yield by coupling of two monomers, followed by hydrogenolysis of benzyl ether protecting groups. Trimer 3 was obtained in 35% yield via a [2 + 1] coupling and tetramer 4 in 15% yield via a [2 + 2] fragment condensation. Circular dichroism spectra show that monomer 1 displays no organized structure, whereas compounds 2–4 show a strong negative band at 200 nm and a weak positive band at ∼220 mn, as is characteristic of the polyproline II helix.