Scheme 4.

Synthesis of thymidine analogues 23 and 24.

Reagents and Conditions: (i) (a) Acetone, H⁺; (b) TBDPSCl, TEA, DMAP, CH₂Cl₂; (c) PCC, CH₂Cl₂, 77% for the three steps; (ii) PhLi, THF, −78 °C, 2 h, 79%; (iii) CH₂=CHCH₂TMS, ZnBr₂, CH₃NO₂, 0 °C then rt, 2 h, 82%; (iv) (a) aq. OsO₄, NaIO₄, pyridine, rt, 30 h; (b) H₂SO₄ (5%), THF, 60 °C, 6 h, 28% for the two steps; (v) Ac₂O, pyridine, 0 °C, 39 h, 90%; (vi) HDMS, TMSCl, SnCl₄, thymine, CH₃CN, 50 °C, 4 h, 21: 42%; 22: 37%; (vii) (a) TBAF, THF, rt, 2 h; (b) NaOH, THF, MeOH, 0 °C, 1 h, 23: 71%; 24: 47% for the two steps.