2'3'-Carbonates in the synthesis of uridine 5'-deoxy and 2',5'-dideoxy derivatives

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Abstract
Detritylation of 2′3′-O-carbonyl-5′-O-trityluridine (Ia) with ethereal hydrogen chloride affords 2′,3′-O-carbonyluridine (Ib; 83%) which is converted by mesylation to the 5′-mesylcarbonate Ic (75%). Reaction of compound Ic with tetrabutylammonium bromide in DMF affords the 5′-bromo carbonate Id (77%) which is reduced with tributyltin hydride to the 5′-deoxyuridine 2′,3′-cyclic carbonate Ie (70%). When heated with imidazole, compound Ie affords the 2,2′anhydro derivative IIa (76%) which is converted to the 2-chloro derivative IIIa (88%) on heating with HCl/DMF. The tributyltin hydride reduction of compound IIIa gives 2′,5′-dideoxyuridine (IIIb; 68%). When heated with NaHCO3 in DMF, the 5′-bromo carbonate Id affords the anhydro bromo derivative IIb (50%) which is converted to the 2′5′-dichloro derivative IIIc (86%) on heating with HCl/DMF. The tributyltin hydride reduction of compound IIIc affords the 2′,5′-dideoxy derivative IIIb (59%). Alkaline hydrolysis of the 2,2′-anhydro derivative IIa affords the arabinosyl derivative IVa which is converted to the diacetyl derivative IVb (34%) by acetylation. When refluxed in water, the 2′,3′-cyclic carbonates Ib, Id, and Ie are hydrolysed to the parent nucleosides, namely, uridine (Va; 81%), 5′-bromo-5′-deoxyuridine (Vb; 78%), and 5-deoxyuridine (Vc; 83%). Hydrolysis of carbonates Ib and Ie is accompanied by the formation of the 2,2′-anhydro derivatives IIc (10%) and IIa (5%) as by-products.