Fig. 2. Synthesis of 3′-phosphate-dTTP 5 and 3′-phosphate-LNA-TTP 10.
A Synthetic scheme for the synthesis of nucleotide 5 and (B) synthetic pathway leading to nucleotide 10. Reagents and conditions: (i) ETT, CH3CN, H2O (9:1), rt, 10 min, quantitative for both 2 and 7; (ii) I2, pyridine, H2O (9:1), rt, 60 min, quantitative for both 3 and 8; iii) TFA, DCM, rt, 60 min, 4 (84%), 9 (97%); iv) 2-chloro-1,3,2-benzodioxaphosphorin-4-one, pyridine, dioxane, rt, 45 min; 2. (nBu3NH)2 H2P2O7, DMF, nBu3N, rt, 45 min; 3. I2, pyridine, H2O, rt, 30 min; 4. NH4OH, MeNH2 (1:1), rt, 2 h, 12% over 4 steps for both 5 and 10.