## 2 Materials and Methods
### Synthesis of the Nucleoside Derivatives
#### Synthesis of 4-amino-6-oxo-1-(3',5'-O-t-butyldimethylsilyl-2',4'-dideoxy-p-ribityl) triazine (4)
The crude product was purified by chromatography on silica gel, eluting with CHCl\({}_{3}\) and 1% Et\({}_{3}\)N, then CH\({}_{3}\)OH/CHCl\({}_{3}\), 1:200 with 1% Et\({}_{3}\)N to give **9** (80 \(\mu\)mol, 70%) as a colorless oil: \({}^{1}\)H-NMR (600 MHz, CDCl\({}_{3}\)) \(\delta\) 7.72 (br, 1H), 7.39-7.38 (m, 2H), 7.30-7.27 (m, 6H), 7.21-7.19 (m, 1H), 6.83-6.80 (m, 2H), 4.20 (dt, 1H, \(J\) = 13.2, 7.2 Hz), 4.04 (dt, 1H, \(J\) = 13.2, 7.2 Hz), 3.15 (dt, 1H, \(J\) = 16.8, 7.2 Hz), 3.06 (dt, 1H, \(J\) = 16.8, 7.2 Hz), 3.06 (dt, 1H, \(J\) = 16.8, 7.2 Hz), 2.96 (t, 2H, \(J\) = 7.2 Hz), 2.60 (s, 3H), 2.54 (t, 2H, \(J\) = 7.2 Hz), 1.96-1.91 (m, 1H), 1.83-1.77 (m, 1H), 1.69-1.66 (m, 2H), 1.57 (qt, 2H, \(J\) = 7.2 Hz), 1.37-1.26 (m, 10H), 0.87 (t, 3H, \(J\) = 7.2 Hz), 1.3C-NMR (150 MHz, CDCl\({}_{3}\)) \(\delta\) 172.0, 170.8, 161.6, 158.5, 155.3, 144.5, 135.7 135.6, 129.88, 129.86, 128.0, 127.9, 126.9, 113.2, 86.9, 68.4, 62.4, 55.2, 42.1, 36.5, 35.5, 34.1, 32.6, 31.8, 29.5, 29.19, 29.17, 28.8, 25.9, 22.6, 14.1; HRMS (ESI) calcd. for C\({}_{41}\)H\({}_{54}\)N\({}_{4}\)O\({}_{5}\)S\({}^{+}\) [M + H]\({}^{+}\)\(m\)/z 731.3837, found _m/z_ 731.3834. 2.6 Synthesis of 2-(2-octylthioethyl)-6-oxo-4-acetylamino-1-(3'-\(N\),\(N\)-diisopropyl cyanoethyl-phosphoramidyl-5'-O-(4,4'-dimethoxytriyl)-2',4'-dideoxy-p-ribityl) triazine (10)  
DIPEA (83.2 \(\mu\)L, 14.3 \(\mu\)mol) was added to a solution of **9** (15.2 mg, 20.8 \(\mu\)mol) in CH\({}_{2}\)Cl\({}_{2}\) (416 \(\mu\)L) and the mixture was cooled to 0 \({}^{\circ}\)C. NCCCH\({}_{2}\)CH\({}_{2}\)OP[(N(i\)-Pr)\({}_{2}\)Cl] (9.3 \(\mu\)L, 41.6 \(\mu\)mol) was then added to the mixture. After the addition, the mixture was stirred at 0 \({}^{\circ}\)C for 1 h, diluted with CH\({}_{2}\)Cl\({}_{2}\), then quenched with NaHCO\({}_{3}\). The product was extracted with CH\({}_{2}\)Cl\({}_{2}\) and the combined organic layer was washed with brine, dried over Na\({}_{2}\)SO\({}_{4}\), filtered and evaporated. The crude product was co-evaporated with toluene, then purified by chromatography on silica gel, eluting with EtOAc/hexane, 1:1 with 1% Et\({}_{3}\)N, then 2:3 with 1% Et\({}_{3}\)N to give **10** (15.0 \(\mu\)mol, 72%) as a colorless oil mixture of two diastereomers: \({}^{1}\)H-NMR (600 MHz, CDCl\({}_{3}\)) \(\delta\) 7.65 (br, 1H), 7.41 (d, 2H, \(J\) = 7.2 Hz), 7.31-7.27 (m, 6H), 7.21-7.18 (m, 1H), 6.83-6.81 (m, 4H), 4.22-4.04 (m, 3H), 3.82-3.49 (m, 4H), 3.79 (s, 6H), 3.22-3.15 (m, 2H), 3.10-2.95 (m, 2H), 2.91-2.86 (m, 2H), 2.64-2.61 (m, 1H), 2.62-2.61 (m, 3H), 2.55-2.50 (m, 2H), 2.48-2.46 (m, 1H), 2.01-1.77 (m, 4H), 1.59-1.54 (m, 2H), 1.39-1.25 (m, 10H), 1.16-1.03 (m, 12H), 0.88 (t, 3H, \(J\) = 7.2 Hz); \({}^{13}\)C-NMR (150 MHz, CDCl\({}_{3}\)) \(\delta\) 172.04, 172.00, 170.4, 170.2, 161.44, 161.40, 158.3, 154.9, 154.7, 145.10, 145.05, 136.32, 136.30, 136.29, 136.27, 130.0, 128.1, 128.0, 127.7, 126.6, 118.0, 117.6, 113.0, 86.0, 77.2, 77.0, 76.8, 70.4, 70.3, 70.0, 69.9, 60.4, 60.0, 58.0, 57.8, 57.4, 57.3, 55.18, 55.15, 43.08, 43.05, 43.00, 42.97, 42.0, 41.9, 36.82, 36.80, 36.25, 36.23, 34.4, 34.3, 34.2, 34.04, 33.95, 32.82, 32.79, 31.8, 29.53, 29.52, 29.18, 29.16, 28.84, 28.83, 27.7, 25.9, 24.80, 24.75, 24.60, 24.56, 24.52, 24.50, 22.6, 21.1, 20.50, 20.45; \({}^{31}\)P- NMR (202 MHz, CDCl\({}_{3}\)) \(\delta\) 147.70, 146.72; HRMS (ESI) calcd. for C\({}_{50}\)H\({}_{71}\)N\({}_{6}\)O\({}_{7}\)PS\({}^{+}\) [M + H]\({}^{+}\)\(m\)/z 931.4915, found _m/z_ 931.4919.