Synthesis of -linked α-Gal and α-GalNAc-1'-hydroxyalkanes by way of C2 functionality transfer.
Nolen EG, Hornik ES, Jeans KB, Zhong W, LaPaglia DM
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Inspired by reports of water sculpted Tn antigen (α-GalNAc--Ser/Thr) epitopes and our interest in producing metabolically more stable -linked analogs of Tn, we explored the utility of C2 functionality on α-Gal--alkenes to deliver hydroxyl to the pendant alkenyl chain. Toward this end, a cyclic carbonate approach gave rise to a single -linked α-Gal-1'(S)-hydroxyethane in 3 steps, and use of a 2-(hydroxyimino)galactoside cyclization transferred an oxygen to a pendant -substituted -linked alkene affording the -configuration at the newly formed stereocenter (7:1 dr). Reduction and acetylation of the resultant isoxazoline demonstrated this approach as a viable route to -linked α-GalNAc-1'-hydroxyalkanes.