I. Synthesis of conformationally restricted nucleosides. II. Studies toward the total synthesis of (-)-neplanocin A

The recent spurt of in interest in conformationally restricted nucleosides has brought into focus concern for the development of spirocyclic nucleosides as potential drug candidates and as potential modulators of DNA conformation and stability. Herein a convenient synthesis a number of spirocyclic nucleosides is detailed. This new class of nucleosides has examples in four different series; sddN, sd4N, sN (RNA), and sdN (DNA). Three unique synthetic strategies were utilized in the development of all four series, with incorporation of all five natural nucleobases.; The pyrimidine bases uracil and thymine were introduced via Vorbrüggen glycosidation conditions utilizing a C2′ sulfide to give the beta anomer exclusively. These sulfides were used in a divergent manor to produce three series, sddN, sd4N, and sN by using the sulfide as a handle for further functionalization about the tetrahydrofuran ring. For the synthesis of these same three series with the purine bases adenine and guanine, use was made of S_N2 displacement of two different anomeric chlorides with the sodium salt of the adenine and guanine precursors.; The final series sdN or DNA analogues began with an α,β-unsaturated lactone. The olefin was dihydroxylated and selectively deoxygenated to give the C2′ deoxy system. Introduction of thymine, cytosine and adenine via Vorbrüggen glycosidation conditions resulted in anomeric mixtures.; A study toward the synthesis of (−)-neplanocin A was undertaken. The synthesis began by the conversion of methyl D-glucopyranoside into a fully protected methyl D-allopyranoside. The protected allopyranoside was then converted into a vinyl sugar needed for a zirconocene mediated ring contraction.