%0 Journal Article
%T C4'-CF<sub>3</sub>-α-L-脱氧胸苷亚磷酰胺单体的合成<br>Synthesis of C4'-CF<sub>3</sub>-α-L-Deoxythymidine Phosphoramidite
%A 周逸飞
%A 闫志国
%J Hans Journal of Chemical Engineering and Technology
%P 137-146
%@ 2161-8852
%D 2019
%I Hans Publishing
%R 10.12677/HJCET.2019.92020
%X 化学修饰是改善反义核酸成药性的重要手段。在本文的研究中，采用化学合成的方法，以已知的化合物(S)-1,3-二(苄氧基)-4-(1,3-二噻烷-2-基)丁-2-酮为原料，经过4步反应，得到苄基保护的C4'-CF<sub>3</sub>-β-L-脱氧胸苷5a和C4'-CF<sub>3</sub>-α-L-脱氧胸苷5b。然后通过氯化钯催化氢化脱除5b的苄基保护基，制得C4'-CF<sub>3</sub>-α-L-脱氧胸苷6。通过核磁共振<sup>1</sup>H谱、<sup>13</sup>C谱、<sup>19</sup>F谱和二维NOESY谱，确认了5a，5b和6的结构以及C4'和C1'的构型。经过两步常规反应，将6转化为C4'-CF<sub>3</sub>-α-L-脱氧胸苷亚磷酰胺8，并使用<sup>1</sup>H谱，<sup>31</sup>P谱，ESI-MS高分辨率质谱确定了最终目标产物8的结构正确性。<br />
Chemical modification is an essential approach to make antisense oligonucleotides drug-like mol-ecules. In this paper, we report the synthesis of C4'-CF<sub>3</sub>-α-L-deoxythymidine phosphoramidite. The synthesis started from the known compound 1, which was efficiently transformed to benzylation protected C4'-CF<sub>3</sub>-β-L-deoxythymidine 5a and C4'-CF<sub>3</sub>-α-L-deoxythymidine 5b in four steps. Debenzylation of 5b using PdCl<sub>2</sub>/H<sub>2</sub> afforded C4'-CF<sub>3</sub>-α-L-deoxythymidine 6. Based on 1D <sup>1</sup>H, <sup>13</sup>C, <sup>19</sup>F and 2D NOESY NMR spectra, the structures of 5a, 5b and 6 were unambiguously characterized. Compound 6 was converted to the phosphoramidite in two routine reaction steps, and the structure of target product 8 was confirmed by <sup>1</sup>H NMR spectrum, <sup>131</sup>P NMR spectrum, and ESI-MS high resolution mass spectrometry.
%K 化学修饰，反义核酸，合成，C4'-CF<sub>3</sub>-α-L-脱氧胸苷<br>Chemical Modification
%K Antisense Oligonucleotides
%K Synthesis
%K C4'-CF<sub>3</sub>-α-L-Deoxythymidine
%U http://www.hanspub.org/journal/PaperInformation.aspx?PaperID=29510