Synthesis of Oxepane Ring Containing Monocyclic, Conformationally Restricted Bicyclic and Spirocyclic Nucleosides from d-Glucose: A Cycloaddition Approach

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/-pyran ring systems upon intramolecular nitrone cycloaddition reactions. Deprotection of the 1,2-acetonides of these derivatives followed by introduction of
uracil base via Vorbrüggen reaction condition and cleavage
of the isooxazolidine rings as well as of benzyl groups by
transfer hydrogenolysis yielded an oxepane ring containing
bicyclic and spirocyclic nucleosides. The corresponding
oxepane based nucleoside analogues were prepared by
cleavage of isoxazolidine and furanose rings, coupling of
the generated amino functionalities with 5-amino-4,6-dichloropyrimidine, cyclization to purine rings, and finally aminolysis.