Department of Chemistry, The University of Chicago, 929 E. 57th St., Chicago, Illinois, 60637 United States.
J Org Chem. 2011 May 20;76(10):4182-8. doi: 10.1021/jo200566d. Epub 2011 Apr 14.
5-Hydroxymethylcytosine (5-hmC) is a newly discovered DNA base modification in mammalian genomic DNA that is proposed to be a major epigenetic mark. We report here the syntheses of two new versions of phosphoramidites III and IV from 5-iodo-2'-deoxyuridine in 18% and 32% overall yields, respectively, with TBDMS as the 5-hydroxyl protecting group. Phosphoramidites III and IV allow efficient incorporation of 5-hmC into DNA and a "one-step" deprotection procedure to cleanly remove all the protecting groups. A "two-step" deprotection strategy is compatible with ultramild DNA synthesis, which enables the synthesis of 5hmC-containing DNA with additional modifications.
5-羟甲基胞嘧啶（5-hmC）是一种在哺乳动物基因组 DNA 中发现的新的 DNA 碱基修饰，被认为是一种主要的表观遗传标记。我们在此报告了分别以 18%和 32%总收率，从 5-碘-2'-脱氧尿苷合成两种新的亚磷酰胺 III 和 IV 的方法，其中 TBDMS 为 5-羟基保护基。亚磷酰胺 III 和 IV 允许 5-hmC 有效地掺入 DNA 中，并通过“一步”脱保护程序干净地去除所有保护基。“两步”脱保护策略与超温和的 DNA 合成兼容，这使得可以合成带有其他修饰的 5hmC 含量的 DNA。
