Synthesis of oxepane ring containing monocyclic, conformationally restricted bicyclic and spirocyclic nucleosides from d-glucose: a cycloaddition approach

Tripathi, S., Roy, B. G., Drew, M.G.B., Achari, B. and Mandal, S.B. (2007) Synthesis of oxepane ring containing monocyclic, conformationally restricted bicyclic and spirocyclic nucleosides from d-glucose: a cycloaddition approach. Journal of Organic Chemistry, 72 (19). pp. 7427-7430. ISSN 0022-3263 doi: 10.1021/jo070846m

Abstract/Summary

Carbohydrate-derived substrates having (i) C-5 nitrone and C-3-O-allyl, (ii) C-4 vinyl and a C-3-O-tethered nitrone, and (iii) C-5 nitrone and C-4-allyloxymethyl generated tetracyclic isoxazolidinooxepane/-pyrart ring systems upon intramolecular nitrone cycloaddition reactions. Deprotection of the 1,2acetonides of these derivatives followed by introduction of uracil base via Vorbruggen reaction condition and cleavage of the isooxazolidine rings as well as of benzyl groups by transfer hydrogenolysis yielded an oxepane ring containing blicyclic and spirocyclic nucleosides. The corresponding oxepane based nucleoside analogues were prepared by cleavage of isoxazolidine and furanose rings, coupling of the generated amino functiontalities with 5-amino-4,6-dichloropyrimidine, cyclization to purine rings, and finally aminolysis.