## 3 Materials and Methods
### Chemistry
#### 3.1.3 Synthesis of \(N\alpha\)-Fmoc-tyrosine-allyl ester (5)  
A solution of allyl ester **4** (10.8 g, 22 mmol) in a mixture TFA:DCM (7:3, \(v\)/\(v\)) was stirred for 30 min at room temperature. Toluene (50 mL) was added and the solvents were removed. The residue was purified on a silica gel column (toluene:EtOAc, 9:1) to yield 7.7 g (79%) of **5**. HPLC (system A): 5.09 min (93% analytical purity). \({}^{1}\)H-NMR (400 MHz, CDCl\({}_{3}\)) \(\delta\): 3.02 (dd, 1 H, \(J\) = 14.0, 6.1 Hz, CH\({}_{2a}\)\(\beta\)), 3.09 (dd, 1 H, \(J\) = 14.0 y 5.6 Hz, CH\({}_{2b}\)\(\beta\)), 4.20 (t, 1 H, \(J\) = 7.0 Hz, CH Fmoc), 4.36 (dd, 1 H, \(J\) = 10.6, 6.9 Hz, CH\({}_{2a}\) Fmoc), 4.43 (dd, 1 H, \(J\) = 10.6 y 7.3 Hz, CH\({}_{2b}\) Fmoc), 4.66 (m, 3 H, CH\({}_{2}\) All, CH \(\alpha\)), 5.28 (m, 3 H, CH\({}_{2}\) All, NH), 5.88 (m, 1 H, CH All), 6.72 (d, 2 H, \(J\) = 8.3 Hz, Ar Tyr), 6.95 (d, 2 H, \(J\) = 8.3 Hz, Ar Tyr), 7.31 (t, 2 H, \(J\) = 7.4 Hz, Ar Fmoc), 7.40 (t, 2 H, \(J\) = 7.4 Hz, Ar Fmoc), 7.57 (m, 2 H, Ar Fmoc), 7.76 (d, 2 H, \(J\) = 7.5 Hz, Ar Fmoc). HRMS: [C\({}_{2}\)H\({}_{25}\)NO\({}_{5}\)]\({}^{+}\); calcd. 443.1736, found 443.1733. \(\alpha_{\rm D}\) (CHCl\({}_{3}\)) = +14.6\({}^{\circ}\). HRMS. \(\alpha_{\rm D}\) (CHCl\({}_{3}\)) = +21.3\({}^{\circ}\), \(\alpha_{\rm D}\) (CHCl\({}_{3}\))\({}^{12}\) = +16.8\({}^{\circ}\). 1.4 Synthesis of 2-cyanoethyl-(N\(\alpha\)-Fmoc-tyrosine-4-yl-allyester)-(\(2^{\prime}\)3\({}^{\prime}\)-di-\(O\)-acetylluridyl-5\({}^{\prime}\)-yl)phosphate (12)  
Phosphoramidite **8** was prepared by reacting \(2^{\prime}\)3\({}^{\prime}\)-di-\(O\)-acetylluridine (1.15 g, 3.52 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 with 5% NaHCO\({}_{3}\) (2 \(\times\) 20 mL). The organic phase was dried (MgSO\({}_{4}\)) and concentrated to yield **8**, which was used in the next step without further purification. HPLC (system B): 4.68 min (96% analytical purity). Approximately 1 mmol of **8** was added to a solution of \(N\alpha\)-Fmoc-tyrosine-allyl ester (5) (443 mg, 1 mmol) in MeCN (10 mL). 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 (MgSO\({}_{4}\)). The solvent was removed under reduced pressure, and the residue was purified by flash column chromatography (DCM:MeOH, 98:2) to obtain 505 mg (57%) of **12**. HPLC (system B): 8.85 min (91% analytical purity).\({}^{1}\)H-NMR (400 MHz, DMSO-d\({}_{6}\)) \(\delta\): 2.06 (s, 6 H, COCH\({}_{3}\)), 2.85 (m, 1 H, CH\({}_{2\text{a}}\) \(\delta\)), 2.94 (t, 2 H, \(J\) = 5.8 Hz, CH\({}_{2\text{C}}\)N), 3.06 (m, 1 H, CH\({}_{2\text{b}}\) \(\delta\)), 4.20 (t, 1 H, \(J\) = 7 Hz, CH Fmoc), 4.25-4.71 (m, 10 H, CH\({}_{2\text{F}}\) Fmoc, CH\({}_{2}\) All, CH\({}_{2\text{C}}\)H\({}_{\alpha}\)CN, CH\({}_{\alpha}\), H-4', H-5'), 5.12-5.37 (m, 3 H, H-2', CH\({}_{2\text{A}}\) All), 5.37-5.45 (m, 1 H, H-3'), 5.58-5.79 (m, 1 H, H-5'), 5.82-5.96 (m, 1 H, CH All), 6.00-6.13 (m, 1 H, H-1'), 7.04-7.20 (m, 4 H, Ar Tyr), 7.26-7.34 (m, 2 H, Ar Fmoc), 7.35-7.45 (m, 3 H, Ar Fmoc, H-6), 7.53-7.62 (m, 2 H, Ar Fmoc), 7.76 (m, 2 H, Ar Fmoc). \({}^{31}\)P-NMR (162 MHz, DMSO-d\({}_{6}\)) \(\delta\): -6.18, -5.82. HRMS: [C\({}_{43}\)H\({}_{43}\)N\({}_{4}\)O\({}_{15}\)P]\({}^{+}\); calcd. 886.2463, found 886.2463.