Synthesis of cycloSal-(Glycopyranosyl-6)-phosphates as Activated Sugar Phosphates

The synthesis of cycloSal‐masked glycopyranosyl phosphates demands suitably protected precursors. A highly regioselective strategy for the preparation of cycloSal‐(1,2,3,4‐tetra‐O‐acetylglycopyranosyl‐6)‐phosphates was developed. Intermediate introduction of the Fmoc‐group allowed the isolation of the 1,2,3,4‐tetra‐O‐acetyl glycopyranoses to be skipped, thus, no isomerization occurred. Glycopyranoses were first converted into the 6‐O‐TBDMS‐1,2,3,4‐tetra‐O‐acetyl derivatives then, in a one‐pot reaction, the silyl ether was cleaved and the resulting 1,2,3,4‐tetra‐O‐acetyl glycopyranoses were trapped with Fmoc‐chloride. In this exchange of protecting groups no acetyl group migration occurred. The 6‐O‐Fmoc‐protected intermediates were selectively converted into the cycloSal‐masked glycopyranosyl phosphates in a one‐pot reaction. Finally, the reactivity of these activated glycopyranosyl‐6‐phosphates was demonstrated in the synthesis of 1,6‐diglycopyranosyl‐phosphates. The preparation of 6‐Fmoc‐protected glycopyranoses succeeded with up to 83 % yield starting from the corresponding glycopyranoses. With this strategy, the migration of acetyl groups can be avoided and the acceptor‐substituted cycloSal phosphate triesters were prepared regioselectively. These activated glycopyranosyl‐6‐phosphates can be used in coupling reactions with nucleophiles.