Conformationally constrained purine mimics. Incorporation of adenine and guanine into spirocyclic nucleosides.
Directed syntheses of spirocyclic nucleosides featuring adenine and guanine as the nucleobases have been successfully developed. The key starting materials are the enantiomerically pure spiro lactones 4, 15, and 28, which have proven amenable to conversion to anomeric mixtures of chloro sugars. The latter can enter into glycosidation by SN2 displacement with the sodium salts of 6-chloropurine or 2-amino-6-chloropurine. In the saturated series, the chromatographic separation of 18 from 19 was possible. Where 33 and 34 are concerned, their relatively rapid rate of epimerization precluded this. Mimics 35-37 resisted isolation as pure anomers. The configurational assignments are based on the thermal interconversions and supporting MM3 steric energy calculations. Added corroboration was gained from a crystallographic analysis of 8. Although removal of the TBS protecting groups in all late-stage guanine intermediates proved to be problematical, the pair of hydroxyl groups in 37 could be introduced by proper recourse to the oxidation of 36 with ruthenium tetraoxide.
Paquette
Leo A
LA
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu
Kahane
Alexandra L
AL
Seekamp
Christopher K
CK
D000225:Adenine / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*
D009705:Nucleosides; D006147:Guanine; D000225:Adenine