5′-Halogeno-2′,3′-cyclic sulphite isomers in the preparation of 5′-halogeno nucleosides. Synthesis of 5′-deoxyuridine and 5′-deoxy-5-fluorouridine
- 1 January 1978
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 5 (3) , 1029-1040
- https://doi.org/10.1093/nar/5.3.1029
Abstract
When uridine (Ia) is reacted with thionyl chloride in hexamethylphosphoric triamide a mixture of isomeric 5'-chloro-2',3'-sulphites is formed, which can be separated to individual epimers IIa and IIIa, in 45% and 15% yields, respectively. Analogously, crystalline epimers IIb (37%) and IIIb (17%) can be obtained from 5-fluorouridine (Ib). Both isomers IIa, IIIa (or IIb, IIIb) afford a single 5'-chloro derivative IVa (or IVb, respectively) if treated with 0.1N sodium methoxide. From the mixture of sulphites IIa and IIIa (or IIb and IIIb) crystalline 5'-chlorouridine IVa is formed in 84.5% yield, calculated per starting uridine Ia (or crystalline 5'-chloro-5-fluorouridine IVb, 85.5% per starting 5-fluorouridine Ib, respectively). On reduction of 5'-chlorouridine IVa with tributyltin hydride 5'-deoxyuridine (Va) is formed in 79% yield. During the reduction of 5'-chloro-5-fluoro derivative IVb to 5'-deoxy-5-fluorouridine (Vb, 57%) a partial reductive elimination of 5-fluorine takes place under formation of 5'-deoxyuridine (Va, 9%).Keywords
This publication has 4 references indexed in Scilit:
- 2'3'-Carbonates in the synthesis of uridine 5'-deoxy and 2',5'-dideoxy derivativesNucleic Acids Research, 1976
- Chemical synthesis and properties of analogs of adenosylcobalaminBiochemistry, 1974
- Direct halogenation of sugar moiety of nucleosidesTetrahedron Letters, 1971
- On the reaction of vilsmeier-haack reagent with nucleoside: a convenient synthesis of 2,2′-cyclocytidineTetrahedron Letters, 1970