多種缩合条件在合成核苷中的应用.docVIP

多种缩合条件在合成核苷中的应用 近些年来，核苷由于其有很好的生物活性和化学治疗特性在抗病毒及抗癌方面常作为潜药被报道出来，这使得在近年来化学合成核苷变得盛行起来。许多新的核苷类药物不断的被合成出来，本文主要报道多种缩合条件在核苷的C-N 键偶联方面的应用,具体有以下几种方法： 1. To a pre-cooled (0oC) solution of compound 1 (0.479 mol), Base (0.719 mol) in 6000 mL CH3CN were added DBU (0.985 mol) at 0 o C and stirred for 30 mins, Then followed by TMSOTf (1.916 mol) dropwise. The mixture was stirred at 70 o C for 8 hrs. TLC showed reaction was completed. The solution was poured into a mixture of EtOAc and NaHCO3 solution. The solution was extracted with EtOAc and washed with brine, then dried with Na2SO4. The solvent was removed and the residue was purified by column. 2 To a pre-cooled (0oC) solution of compound 1 (1 mmol) and Base (1.5 mmol) in 30 mL CH3CN were added BSA (2 mmol) at 0 oC and stirred for 10 mins, Then followed by TMSOTf (3 mmol) dropwise. The mixture was stirred at 70 oC for 8 hrs. TLC showed reaction was completed. The solution was poured into a mixture of EtOAc and NaHCO3 solution. The solution was extracted with EtOAc and washed with brine, then dried with Na2SO4. The solvent was removed and the residue was purified by column. 3. To a solution of compound 1 (1 mmol) and TEA (3 mmol) in anhydrous DCM (4 mL) is stirred at 30oC for 10 min. Then the mixture is added dropwise of Ms2O (1.3 mmol, dissolved in 1mL DCM) for 10 min. The reaction is stirred at 40 oC for 2.5 h. Then the mixture is added DCM (50 mL), washed with H2O（50 mL）, brine (50mL). The organic layer is dried, evaporated to dyness to afftod the crude product. To a flask charged with Base (1.48 mmol) are added NaH (1.48 mmol) and ACN (4mL), stirring for 10 mins. Crude compound 2 (0.74 mmol) dissolved in ACN (2 mL ) is added and the reaction is heated to 50 oC for 15 h. The mixture is adjusted to PH=7.0 by 1N HCl and evaporated to under vacuum. EtOAc (50 mL) is added to the residue solution and it is washed with 1N HCl (8mL), brine (10mL),dried, evaporated to dryness and purified by column to afford the desired