Nitrogen inversion as a diastereomeric relay in azasugar synthesis: the first synthesis of adenophorine.

Although amine nitrogen atoms are potential stereogenic centers, their configurational lability arising from lone-pair inversion has typically prevented their utility in synthesis.NHalogenation can dramatically slow lone-pair inversion and therefore raise the temperature at which the configurational lability ceases. We therefore considered that if a suitable system could be found, N-chloramines might provide a new source of flexible, temperature-dependent stereogenesis. In turn, existing chiral information may then be relayed and exploited such that subsequent reactions are regioor diastereoselective. Due to the often higher conformational lability of the acyclic N lone-pair isomers ofN-haloamines, we selected cyclic amines for our study, which are typically, but not always, less labile due to angular constraint. Cyclic systems have often been exploited for intramolecular relay of chirality. As our model chiral cyclic N-chloramine system we selected N-chloropiperidine azasugars. Polyhydroxylated nitrogen heterocycles such as deoxynojirimycin (DNJ, 1 in Scheme 1) may be considered to be mimics of sugars, for example, d-glucose, in which the ring oxygen has been replaced by a nitrogen atom. The often potent inhibitory activity of many of these compounds towards carbohydrateprocessing enzymes has suggested their use in a wide range of potential therapeutic strategies, including the treatment of viral infections and lysosomal storage diseases, and as invaluable tools in the study of enzyme mechanism.