Fig. 4

Thiolysis and oxidation of pyrimidine nucleosides. a i. H₂S thiolysis of arabino-anhydrocytidine (3C) in water (pH 7) furnished β-arabino-cytidine (ara-4C; quant.) rapidly; ii. ara-4C then undergoes slow addition of H₂S to afford 4-thio-β-arabino-uridine (ara-7U). iii. H₂O₂ oxidation of ara-7U in water (pH 7) furnished arabino-uridine (ara-4U, 78%). iv. Thiolysis of 3C in formamide yielded 2-thio-β-arabino-cytosine (ara-6C, 31%). v. H₂O₂ oxidation of ara-6C in water (pH 7) furnished 3C (quant.). b i–ii. H₂S thiolysis of ribo-anhydrocytidine (α-ribo-3C) in water (pH 7) furnished α-ribo-cytidine (α-ribo-4C), which then undergoes addition of H₂S to afford 4-thio-α-ribo-uridine (α-ribo-7U) in 91% combined conversion. iii. H₂O₂ oxidation of α-ribo-7U in water (pH 7) furnished α-ribo-uridine (α-ribo-4U, 93%). iv–v. Sutherland and co-workers reported the synthesis of 2-thio-β-ribo-cytidine (β-ribo-6C) by thiolysis of ribo-anhydrocytidine (α-ribo-3C) in formamide, followed by aqueous irradiation (λ = 254 nm)³⁵. vi. H₂O₂ oxidation of 2-thio-β-ribo-cytosine (β-ribo-6C) furnished canonical ribonucleoside β-cytidine (β-ribo-4C, quant.) between pH 7 and 9. vii. Conversely, H₂O₂ oxidation of β-ribo-6C predominately furnished pyridimide 4-amino-pyrimidine-riboside (β-ribo-9, 76%) at pH 3. viii. Due to the proximity of the nucleobase and C2′-hydroxyl moieties, H₂O₂ oxidation of α-ribo-6C furnished α-ribo-3C (quant.). ix–x. The sequential reaction of H₂S and H₂O₂ with β-ribo-4C in water (pH 7) furnished β-ribo-4U