The synthesis of 6,6′-cyclo-6′-deoxyhexofuranosyluracils via a diazomethane-promoted ring-enlargement reaction

The protected 5′-oxo-6,5′-cyclouridine 13 reacts with diazomethane to afford mostly the spiro-epoxide 18 (79%), but it also undergoes ring-expansion to give the corresponding 5′-oxo-6,6′-cyclonucleoside 16. Under the conditions of the reaction, ketone 16 reacts further with diazomethane to give the enol ether 20 (12% overall), the isomeric 4-methoxy nucleoside 15 (2%), and the spiro-epoxide 19 (4.4%). Acid hydrolysis of the enol ether 20 , followed by reduction of the resulting ketone with sodium borohydride, affords a separable mixture of the 5′S (L-talo) and 5′R (D-allo) methylene-bridged cyclonucleosides 7 and 8 , respectively. From proton nmr measurements, it appears that the 6′-methylene groups of these cyclonucleosides project towards the 2′,3′-edge of the furanose ring.