Synthesis of a Series of Enantiopure Polyhydroxylated Bicyclic N‐Heterocycles from an L‐Erythrose‐Derived Nitrone and Alkoxyallenes

Abstract

AbstractTwo different lithiated alkoxyallenes and the enantiopure L‐erythrose‐derived cyclic nitrone (+)‐3 were used as precursors for the preparation of novel bicyclic 2H‐1,2‐oxazine derivatives, which were formed as single diastereomers. A highly stereoselective hydroboration/oxidation sequence provided key substrates that were suitable for the synthesis of a series of polyhydroxylated bicyclic N‐heterocycles, including unique 5‐oxaindolizidines such as 8 and 12. Depending on the protecting groups installed, a straightforward ring‐opening/recyclization protocol allowed the preparation of the corresponding pyrrolizidines bearing two, three or four free hydroxy groups. By inversion of the order of reaction steps, the synthesis of novel isomeric azabicyclo[3.2.0]heptane derivatives that are the lower homologues of pyrrolizidines and indolizidines were achieved. The prepared novel polyhydroxylated compounds were examined for their property as glycosidase inhibitors, but none of the compounds showed noteworthy activity.