Short synthesis, X-ray and conformational analysis of a cyclic peracetylated l-sorbose-derived nitrone, a useful intermediate towards N–O-containing d-gluco-iminosugars

Abstract

The synthesis of the peracetylated ketonitrone 4 is described in four steps from L-sorbose. This cyclic nitrone is crystalline and proved to preferentially adopt a ⁴H₃ conformation with all acetate groups in pseudo-axial orientation. Nitrone 4 undergoes regioselective cycloadditions with alkynes, affording tetra-O-acetyl-isoxazolines with good yields and stereoselectivities (4 : 1 to 9 : 1 diastereomeric ratio). Nitrone 4 and the obtained isoxazolines were smoothly deacetylated to produce the polyhydroxylated nitrone 5 and novel iminosugars containing an isoxazoline motif. Evaluation of their glycosidase inhibitory activity demonstrated their rather weak, but selective affinity for a variety of enzymes.