Synthesis Of C-Linked Alpha-Gal And Alpha-Galnac-1 '-Hydroxyalkanes By Way Of C2 Functionality Transfer

Inspired by reports of water sculpted Tn antigen (alpha-GalNAc-O-Ser/Thr) epitopes and our interest in producing metabolically more stable C-linked analogs of Tn, we explored the utility of C2 functionality on alpha-Gal-C-alkenes to deliver hydroxyl to the pendant alkenyl chain. Toward this end, a cyclic carbonate approach gave rise to a single C-linked alpha-Gal-1 '(S)-hydroxyethane in 3 steps, and use of a 2-(hydroxy-imino)galactoside cyclization transferred an oxygen to a pendant cis-substituted C-linked alkene affording the R-configuration at the newly formed stereocenter (7:1 dr). Reduction and acetylation of the resultant isoxazoline demonstrated this approach as a viable route to C-linked alpha-GalNAc-1 '-hydroxyalkanes. (C) 2021 The Authors. Published by Elsevier Ltd.