Synthetic Nucleosides and Nucleotides. VI. On the Several Routes for the Syntheses of 4-Thiouridylic Acid Homologues

Abstract

The following synthetic methods for the preparation of 4-thiouridylic acid homologues from uridine are described. Route A. Mild acid treatment of 2', 3'-O-isopropylidene-5'-O-benzoyl-4-thiouridine (II) followed by phosphorylation by Tener's procedure gave 4-thiouridine 2', (3')-phosphate via 5'-O-benzoyl-4-thiouridine (III). Alkali treatment of II followed by phosphorylation by Tener's procedure gave 4-thiouridine 5'-phosphate via 2', 3'-O-isopropylidene-4-thiouridine (IV). Route B. 2', 3'-Di-O-acetyl-5'-O-trityl-4-thiouridine (V) was prepared by thiation of 2, 3'-di-O-acetyl-5'-O-trityluridine. Alkali treatment of V followed by Tener's phosphorylation gave 2', (3')-phosphate of 4-thiouridine via 5'-O-trityl-4-thiouridine (VI). Mild acid treatment of V followed by Tener's phosphorylation gave 5'-phosphate of 4-thiouridine in satisfactory yield via 2', 3'-di-O-acetyl-4-thiouridine (VII). Route C. Direct phosphorylation of 4-thiouridine with excess amounts of cyanoethylphosphate and dicyclohexylcarbodiimide produced 2', (3')-mono-, 5'-mono-and 2', (3'), 5'-diphosphate of 4-thiouridine. Treatment of the diphosphate with dicyclohexylcarbodiimide gave 4-thiouridine 2', 3'-cyclic, 5'-diphosphate (VIII). 4-Thiouridine 2', 3'-cyclic phosphate (IX) was obtained by treatment of 4-thiouridine 2', (3')-phosphate with same manner or by digestion of VIII with E. coli alkaline phosphomonoesterase. 4-thiouridine 3'-phosphate was prepared by digestion of IX with bovine pancreatic ribonuclease.