The Synthesis and Conformation of Dihydroxypiperidinyl Derivates of Nucleobases as Novel Iminosugar Nucleoside Analogs

An optimized method for the synthesis of an important chiral scaffold, (3S,4R,5R)-1-N-Boc-3,4-isopropylidene-3,4,5-trihydroxypiperidine, was developed. Using this intermediate, the preparation of various chiral aminodihydroxypiperidines and their transformation into a series of non-glycosidic, six-membered azanucleosides was accomplished. NMR conformation analysis of the prepared piperidine azanucleosides revealed a preference for the chair conformation, with the nucleobase fixed in the equatorial position in all cases.