Organic Chemistry Portal
Reactions >> Total Syntheses

Totally Synthetic by Paul H. Docherty, 15 December 2009

Total Synthesis of 1-Deoxynojirimycin & 1-Deoxyaltronojirimycin


S. K. Bagal, S. G. Davies, J. A. Lee, P. M. Roberts, A. J. Russell, P. M. Scott, J. E. Thomson, Org. Lett. 2010, 12, 136-139.

DOI: 10.1021/ol902533b

A pair of closely related syntheses provide polyhydroxylated piperidenes, that show glycosidase inhibition. Glycosidase inhibitors have been notable in both anti-cancer and HIV therapies.

The first reaction worth considering is a bis-epoxidation and in situ opening to provide four stereocenters in one pot. The chemistry is racemic, but does an excellent job in a useful yield and with excellent diastereoselectivity.

Taking the freshly installed alcohol and mesylating under standard conditions results in a transannular ring closure, as the proximal amine displaces the mesylate to give an aziridine. As chloride ions are still present, the aziridine is opened to complete a formal ring contraction and provide a functional handle.

AgOAc was used for the displacement of chloride by acetate, setting the group very close to the target, and demonstrating a neat sequence of reactions to produce a heavily functionalised piperidine.