School of Chemistry and Materials Science, Ludong University, Yantai 264025, Shandong Province, P. R. China.
Org Biomol Chem. 2023 Feb 22;21(8):1744-1754. doi: 10.1039/d2ob02070j.
Herein we report the application of 4-alkyl-1,4-dihydropyridines (DHPs), which are easily prepared from inexpensive aldehydes in one step, for the direct site-specific C-H alkylation of purines and purine nucleosides. Despite there being three active C(sp)-H bonds (C-2-H, C-6-H, and C-8-H) in the structure, the reactions still show high regioselectivity at the purinyl C-6-H position. Importantly, the reactions successfully avoid the use of transition metal catalysts and additional acids. Meanwhile, the protocols are not sensitive to moisture and require only persulfate as an oxidant. Besides, this method displays broad functional group compatibility and is easy to scale up. Notably, pharmaceutical purines, the natural product 6-hydroxymethyl nebularine isolated from basidiomycetes, can be smoothly prepared using this protocol.
在此，我们报告了 4-烷基-1,4-二氢吡啶（DHPs）的应用，它可以通过一步反应很容易地从廉价的醛制备得到，用于嘌呤和嘌呤核苷的直接位点特异性 C-H 烷基化。尽管结构中有三个活性 C(sp)-H 键（C-2-H、C-6-H 和 C-8-H），但反应仍在嘌呤基 C-6-H 位置表现出高区域选择性。重要的是，反应成功地避免了使用过渡金属催化剂和额外的酸。同时，该方案对水分不敏感，只需过硫酸盐作为氧化剂。此外，该方法显示出广泛的官能团相容性，并且易于放大。值得注意的是，该方法可以顺利制备出药物嘌呤，以及从担子菌类中分离出的天然产物 6-羟甲基 Nebularine。
