3.1.4. General Procedure for the Synthesis of Conjugates **4**

Morpholino nucleotides **3A-ClU** (TEA salt, 0.05 mmol) and Ph3P (0.15 mmol, 0.039 g) were dissolved in 1,3-dimethyl-2-imidazolidinone (DMI, 0.5 mL). *N*-Methylimidazole (MeIm, 0.6 mmol, 0.05 mL) and (PyS)<sup>2</sup> (0.15 mmol, 0.03 g) were added to the solution, and the reaction mixture was stirred for 15 min. Adenosine 50 -phosphate (*n*-Bu3N salt, 0.2 mmol in 0.5 mL of DMI) was added to the reaction mixture and stirring was continued for 1 h. Conc. aq. NH<sup>3</sup> (2 mL) was added to the reaction mixture in case of the synthesis of conjugates **4A,G,C,** and after the deblocation of heterocyclic bases was completed (24 h at room temperature) the reaction mixture was evaporated up to its initial volume (1 mL). Then the reaction mixture was poured into Et2O (20 mL) and cooled (−20 ◦C, 2 h). The precipitate was separated by centrifugation, washed by Et2O and dried. *N*-Tr-protected conjugates **4A-ClU** were purified by RPC in a linear gradient of MeCN in water in the presence of 0.1 M NH4HCO3. Appropriate fractions were collected and evaporated. Traces of a buffer were removed by repeating the evaporation from aq. EtOH. To remove the Tr protective group, the residue was dissolved in 80% aq. AcOH (1 mL). In 1 h, the conjugates **4A-ClU** were precipitated by 4% NaClO<sup>4</sup> in acetone (10 mL), cooled (−20 ◦C, 2 h), and centrifuged. The precipitate was washed with acetone and dried.

#### 3.1.5. General Procedure for the Synthesis of 20 -aminomethylmorpholino Nucleosides **7**

Morpholino nucleosides **2A-ClU** (0.7 mmol), Ph3P (1.4 mmol, 0.367 g) and imidazole (1.4 mmol, 0.095 g) were dissolved in dichloroethane (DCE) (2.8 mL). The solution was cooled in an ice bath (−5 ◦C). A solution of I<sup>2</sup> (0.9 mmol, 0.23 g) in DCE (0.4 mL) was added under vigorous stirring. The cooling was removed and the reaction mixture was stirred for 5 h at r.t. The reaction mixture was diluted with CH2Cl<sup>2</sup> (20 mL) and washed with aq. 5 M NaHSO<sup>3</sup> (20 mL), sat. aq. NaHCO<sup>3</sup> (20 mL) and water (2×20 mL). The organic layer was dried (Na2SO4), filtered and evaporated. 2<sup>0</sup> -Iodomethylmorpholino nucleosides **5A-ClU** were purified by silica gel chromatography in a gradient of acetone in CH2Cl<sup>2</sup> (0%–20%). Appropriate fractions were combined and evaporated. The residue was dissolved in CH2Cl<sup>2</sup> (1 mL) and precipitated with petroleum ether (15 mL). The suspension was cooled (−20 ◦C, 2 h), the precipitate was separated by centrifugation, washed with petroleum ether and dried under vacuum. Morpholino nucleosides **5A-ClU** (0.5 mmol) were dissolved in DMF (2 mL), then NaN<sup>3</sup> (2.5 mmol, 0.163 g) was added. The suspension was stirred overnight at r.t. and then was diluted with CH2Cl<sup>2</sup> (20 mL) and washed with water (4×10 mL). The organic layer was dried with Na2SO<sup>4</sup> and filtered. The evaporated residue was dissolved in CH2Cl<sup>2</sup> (1 mL) and precipitated by petroleum ether (15 mL). The suspension was cooled (−20 ◦C, 2 h), the precipitate was separated by centrifugation, washed by petroleum ether and dried under vacuum. 10% Pd/C (0.01 mmol, 10 mg) was added to a solution of 20 -azidomethylmorpholino nucleosides **6A-ClU** (0.1 mmol) in MeOH (1 mL). The mixture was stirred for 48 h under H2. The reaction mixture was filtered and evaporated. The residue was dissolved in CH2Cl<sup>2</sup> (0.1 mL) and precipitated by petroleum ether (1.5 mL). The suspension was cooled (−20 ◦C, 2 h), the precipitate was separated by centrifugation, washed by petroleum ether and dried under vacuum.
