A Short Synthesis of Polyhydroxylated Piperidines by Aldol Reaction of Chelated Amino Acid Ester Enolates

Aldol reactions of a chelated glycine ester enolate with a chiral aldehyde gives rise to the corresponding polyhydroxylated amino acid with excellent induced diastereoselectivity. These oxygenated amino acids can be converted into polyhydroxylated pipecolinic acids and azasugars by cyclization using the Mitsunobu reaction. An interesting epimerization was observed during the cyclization. The potential glycosidase inhibitor 1-deoxyaltronojirimycin (8b) was synthesized by this approach in a highly stereoselective fashion.