No abstract

A facile synthesis is reported for five-membered iminocyclitols which allows for variation in stereochemistry at all the chiral centers, diverse C1- and N-substitution, and the potential for a three-component combinatorial process. The key step is inversion at the C4 stereocenter (L-lyxo sugar --> D-ribono azasugar). The exo-imino to endo-iminocyclitol process was extended to the D-lyxo and the D- and L-hexose series. Some analogues were found to be more potent than N-butyl DNJ and N-nonyl DNJ in antiviral activity.

SummaryBy focusing on recent developments on natural and non-natural azasugars (iminocyclitols), this review bolsters the case for the role of olefin metathesis reactions (RCM, CM) as key transformations in the multistep syntheses of pyrrolidine-, piperidine- and azepane-based iminocyclitols, as important therapeutic agents against a range of common diseases and as tools for studying metabolic disorders. Considerable improvements brought about by introduction of one or more metathesis steps are outlined, with emphasis on the exquisite steric control and atom-economical outcome of the overall process. The comparative performance of several established metathesis catalysts is also highlighted.