一种无需保护基团即可将 2,6-二氨基嘌呤和 2-氨基腺嘌呤缀合到寡核苷酸中的化学方法。

Alnylam Pharmaceuticals, 675 West Kendall Street, Cambridge, Massachusetts 02142, United States.

Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, United States.

Org Lett. 2022 Aug 26;24(33):6111-6116. doi: 10.1021/acs.orglett.2c01848. Epub 2022 Aug 16.

We report a simple, postsynthetic strategy for synthesis of oligonucleotides containing 2,6-diaminopurine nucleotides and 2-aminoadenine conjugates using 2-fluoro-6-amino-adenosine. The strategy allows introduction of 2,6-diaminopurine and other 2-amino group-containing ligands. The strongly electronegative 2-fluoro deactivates 6-NH obviating the need for any protecting group on adenine, and simple aromatic nucleophilic substitution of fluorine makes reaction with aqueous NH or R-NH feasible at the 2-position.

我们报告了一种简单的、基于后合成的方法，用于合成含有 2,6-二氨基嘌呤核苷酸和 2-氨基腺嘌呤缀合物的寡核苷酸，该方法使用 2-氟-6-氨基-腺苷。该策略允许引入 2,6-二氨基嘌呤和其他含 2-氨基的配体。强电负性的 2-氟使 6-NH 失活，从而避免了腺嘌呤上任何保护基团的需要，并且氟的简单芳香亲核取代使得与水合 NH 或 R-NH 在 2-位的反应成为可能。