Mikesell Logan, Eriyagama Dhananjani N A M, Yin Yipeng, Lu Bao-Yuan, Fang Shiyue
Department of Chemistry, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA.
ChampionX, 11177 South Stadium Drive, Sugar Land, TX 77478, USA.
Beilstein J Org Chem. 2021 Dec 28;17:2976-2982. doi: 10.3762/bjoc.17.207. eCollection 2021.
The stepwise synthesis of monodisperse polyethylene glycols (PEGs) and their derivatives usually involves using an acid-labile protecting group such as DMTr and coupling the two PEG moieties together under basic Williamson ether formation conditions. Using this approach, each elongation of PEG is achieved in three steps - deprotection, deprotonation and coupling - in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in two steps - deprotection and coupling - in only one pot. The deprotonation step, and the isolation and purification of the intermediate product after deprotection using existing approaches are no longer needed when the one-pot approach is used. Because the stepwise PEG synthesis usually requires multiple PEG elongation cycles, the new PEG synthesis method is expected to significantly lower PEG synthesis cost.
单分散聚乙二醇（PEG）及其衍生物的逐步合成通常涉及使用酸不稳定保护基（如二甲氧基三苯甲基），并在碱性条件下通过威廉姆森醚形成反应将两个PEG部分偶联在一起。采用这种方法，PEG的每次延长需要在两个反应瓶中分三步完成——脱保护、去质子化和偶联。在此，我们报道了一种更简便的PEG合成方法，该方法使用了碱不稳定保护基（如苯乙基）。采用这种方法，PEG的每次延长仅需在一个反应瓶中分两步完成——脱保护和偶联。使用一锅法时，不再需要去质子化步骤以及现有方法中脱保护后中间产物的分离和纯化。由于逐步PEG合成通常需要多个PEG延长循环，因此新的PEG合成方法有望显著降低PEG合成成本。
