1-Deoxynojirimycin and 1-Deoxyaltronojirimycin
Davies, Bagal, Lee, Roberts, Russell, Scott, Thomson. Org. Lett., 2009, ASAP. DOI: 10.1021/ol902533b.
More of a post-ette than a full post, this tasty little nugget was found buried amongst effective reposts and updates. Out there to give you a freaky sense of de ja vous are full papers on kendomycin, spirastrellolide, nakiterpiosin… finding something new was an effort!
What we’ve got here are a pair of closely related synthese of some poly hydroxylated piperidenes; notable for their glycosidase inhibitory effects. Huh, I hear you say (actually, probably not – there are plenty of med-chemists reading this!) – 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 otherwise, garnering a useful yield and excellent diastereoselectivity.
The second reaction I liked followed on directly after this. Taking the freshly installed alcohol and mesylating under standard conditions results in a trans-annular ring closure, as the proximal amine displaces the mesylate to give an aziridine. In the formation of the mesylate, chloride is of course displaced (soaked-up by the triethylamine). But it now comes to the fore, opening the aziridine to complete a formal ring contraction and provide a functional handle.
A bit of silver was sufficient in hydrolysing the primary chloride, setting the group very close to the target, and demonstrating a neat sequence of reactions to produce a heavily functionalised piperidine.