ABSTRACT
The stereoisomeric 3,4,5-trihydroxypiperidines were synthesized by M. Godskesen et al. from the corresponding aldonolactones or aldonic acid ester intermediates bearing a C-5 leaving group on treatment with aqueous ammonia. Y. -F. Chang and coworkers elected to employ a combinatorial approach to a library of pyrrolidine and piperidine iminosugar analogs, via key intermediates followed by their addition to nucleophiles in a diastereoselective fashion. 3,4,5-Trihydropiperidines constitute a family of natural product analogs with wide-ranging and often selective biological activities. Paulsen and coworkers reported the first synthetic approaches to 3,4,5-trihydroxypiperidine from d-xylose derivatives, while studying the equilibria of sugar-derived hemiaminals. Iminosugars 1 and 2 have been synthesized from d-glucose, which was firstly derivatized to 1,2-O-isopropylidene-3-O-benzyl-α-d-xylo-pentodialdose in 68% overall yield. Subsequent sodium borohydride reduction of the C-5 aldehyde, hydroxyl tosylation, and nucleophilic displacement of the tosyl group with sodium azide gave N-bearing intermediate.
