## 3 Materials and Methods
### Chemistry
#### 3.1.3 Synthesis of \(N\alpha\)-Fmoc-tyrosine-allyl ester (5)
1.5 Synthesis of 2-cyanoethyl-(\(N\alpha\)-Fmoc-tyrosine-4-yl-allyester)-(\(2^{\prime}\),\(3^{\prime}\)-di-O-acetyl-5-flurourouridyl-5'-yl) phosphate (13)  
Phosphoramidite **9** was prepared by reacting \(2^{\prime}\),\(3^{\prime}\)-di-O-acetyl-5-fluorouridine (1.21 g, 3.5 mmol), coevaporated with MeCN (2 \(\times\) 5 mL) in DCM (15 mL), containing TEA (2.25 mL, 16.70 mmol), with 2-cyanoethoxy-\(N\),\(N\)-disopropylaminochlorophosphate (0.95 mL, 4.22 mmol) under an argon atmosphere. The reaction mixture was stirred for 30 min at room temperature. DCM (20 mL) was added and the reaction mixture was washed with water (20 mL) and 5% NaHCO\({}_{3}\) (2 \(\times\) 20 mL). The organic phase was dried (MgSO\({}_{4}\)) and concentrated. HPLC (system B): 4.68 min (96% analytical purity). Approximately 1 mmol of **9** was added to a solution of \(N\alpha\)-Fmoc-tyrosine-allyl ester (**5**) (443 mg, 1 mmol) in MeCN (10 mL), then 4,5-dicyanoimidazole (177 mg, 1.5 mmol) was added and the reaction mixture was stirred for 45 min. A solution of tBuOOH (5.5 M in nonane, 0.73 mL, 4 mmol) was added to the reaction mixture and stirred for 45 additional minutes. The reaction mixture was diluted in 25 mL DCM and washed with 5% Na\({}_{2}\)S\({}_{2}\)O\({}_{3}\) (3 \(\times\) 20 mL) and water (20 mL). The organic phase was dried (MgSO4). The solvent was removed under reduced pressure, and the residue was purified by flash column chromatography (DCM:MeOH, 98:2) to obtain 858 mg (42%) of **13**. HPLC (system B): 8.91 min (99% analytical purity). \({}^{1}\)H-NMR (400 MHz, DMSO-d\({}_{6}\)) \(\delta\): 2.05, 2.07 (s, 6 H, COCH\({}_{3}\)), 2.94 (m, 3 H, CH\({}_{2\text{a}}\)\(\delta\), CH\({}_{2\text{C}}\)N), 3.05 (dd, 1 H, \(J\) = 13.7, 5.1 Hz, CH\({}_{2\text{b}}\)\(\beta\)), 4.17-4.34 (m, 7 H, CH\({}_{2}\) Fmoc, CH Fmoc, CH\({}_{2\text{C}}\)H\({}_{2\text{C}}\)N, H-4'), 4.43 (m, 2 H, H-5'), 4.57 (m, 2 H, CH\({}_{2\text{A}}\)\(\Delta\)), 5.18 (dd, 1 H, \(J\) = 10.6, 1.6 Hz, CH\({}_{2\text{a}}\)\(\Delta\)), 5.28 (dd, 1 H, \(J\) = 17.2, 1.6 Hz, CH\({}_{2\text{b}}\)\(\Delta\)), 5.34 (m, 1 H, H-3'), 5.43 (m, 1 H, H-2'), 5.84 (m, 1 H, CH All), 5.93 (d, 1 H, \(J\) = 5.7 Hz, H-1'), 7.15 (d, 2 H, \(J\) = 8.3 Hz, Ar Tyr), 7.26-7.35 (m, 4 H, Ar Fmoc y Tyr), 7.41 (t, 2 H, \(J\) = 7.5 Hz, Ar Fmoc), 7.65 (m, 2 H, Ar Fmoc), 7.88 (d, 2 H, \(J\) = 7.5 Hz, Ar Fmoc), 7.92 (bs, 1H, NH), 8.09 (m, 1H, H-6), 12.0 (bs, 1H, NH). \({}^{13}\)C-NMR (100 MHz, DMSO-d\({}_{6}\)) \(\delta\): 19.0, 19.1 (CH\({}_{2\text{C}}\)N), 20.2, 20.3 (COCH\({}_{3}\)), 35.6 (CH\({}_{2}\)\(\beta\)), 46.6 (CH Fmoc), 55.5 (CH \(\alpha\)), 63.3 (CH\({}_{2}\)CH\({}_{2}\)CN), 64.9 (CH\({}_{2}\) All), 65.6 (CH\({}_{2}\), Fmoc), 67.0 (C-5'), 69.0 (C-3'), 71.5 (C-2'), 79.6 (C-4'), 87.4 (C-1'), 117.8 (CH\({}_{2}\) All), 118.1 (CN), 119.7 (CH Ar Tyr), 120.1 (CH Ar Fmoc), 125.3 (CH Ar Fmoc), 125.2 (C-6, \({}^{2}J\) = 36 Hz), 127.1, 127.7 (CH Ar Fmoc), 130.6 (CH Ar Tyr), 132.2 (CH All), 134.7 (C Tyr), 139.6 (C-5, \({}^{1}J\) = 232.1 Hz), 140.7 (C Fmoc), 143.7 (C Fmoc), 148.6 (C Tyr), 149.1 (C=O C-2), 155.9 (CONH), 156.9 (C=O C-4, \({}^{2}J\) = 26.2 Hz), 169.3 (COCH\({}_{3}\)), 173.3 (C=O Tyr). \({}^{31}\)P-NMR (162 MHz, DMSO-d\({}_{6}\)) \(\delta\): -5.83, -5.87. HRMS: [C\({}_{43}\)H\({}_{42}\)FN\({}_{4}\)O\({}_{15}\)P]\({}^{+}\); calcd. 904.2401, found 904.2402. 1.6 Synthesis of 2-cyanoethyl-(\(N\alpha\)-Fmoc-tyrosine-4-yl)-(\(2^{\prime}\),\(3^{\prime}\)-di-O-acetylluridyl-5'-yl)phosphate (14)  
To a stirred solution of **12** (1.6 g, 1.8 mmol), coevaporated with MeCN (5 mL \(\times\) 2) in 1:1 THF/DCM (10 mL, \(v\)/\(v\)), containing AcOH (0.45 mL, 8 mmol), Bu\({}_{3}\)SnH (0.97 mL, 3.6 mmol) and Pd(PPh\({}_{3}\))\({}_{4}\) (87 mg, 0.08 mmol) were added under an argon atmosphere. After two hours the reaction mixture was concentrated and purified by flash column chromatography (DCM:MeOH, 94:6) to yield **14** (0.99 g, 65%) as white amorphous solid. HPLC (system B): 7.63 min (97% analytical purity).