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 HC1/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 HC1/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.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Falco E. A., Fox J. J. Nucleosides. 48. Synthesis of 1-(5-deoxy-beta-D-arabinosyl)cytosine and related compounds. J Med Chem. 1968 Jan;11(1):148–151. doi: 10.1021/jm00307a035. [DOI] [PubMed] [Google Scholar]
- Hampton A., Nichol A. W. Nucleotides. V. Purine ribonucleoside 2',3'-cyclic carbonates. Preparation and use for the synthesis of 5'-monosubstituted nucleosides. Biochemistry. 1966 Jun;5(6):2076–2082. doi: 10.1021/bi00870a040. [DOI] [PubMed] [Google Scholar]
- Letsinger R. L., Ogilvie K. K. Use of p-nitrophenyl chloroformate in blocking hydroxyl groups in nucleosides. J Org Chem. 1967 Feb;32(2):296–300. doi: 10.1021/jo01288a011. [DOI] [PubMed] [Google Scholar]
- Ruyle W. V., Shen T. Y., Patchett A. A. Nucleosides. II. Reactions of 5'-trityluridine 2',3'-O-thionocarbonate. J Org Chem. 1965 Dec;30(12):4353–4355. doi: 10.1021/jo01023a528. [DOI] [PubMed] [Google Scholar]
- Verheyden J. P., Moffatt J. G. Halo sugar nucleosides. 3. Reactions for the chlorination and bromination of nucleoside hydroxyl groups. J Org Chem. 1972 Jul 14;37(14):2289–2299. doi: 10.1021/jo00979a018. [DOI] [PubMed] [Google Scholar]
- Verheyden J. P., Wagner D., Moffatt J. G. Synthesis of some pyrimidine 2'-amino-2'-deoxynucleosides. J Org Chem. 1971 Jan 29;36(2):250–254. doi: 10.1021/jo00801a002. [DOI] [PubMed] [Google Scholar]