Medicinal Chemistry Division, GVK Biosciences Pvt. Ltd. 28A, IDA Nacharam, Hyderabad 500076, Andhra Pradesh, India.
Chem Asian J. 2012 Aug;7(8):1853-61. doi: 10.1002/asia.201200093. Epub 2012 May 8.
Reaction conditions for the CC cross-coupling of O(6)-alkyl-2-bromo- and 2-chloroinosine derivatives with aryl-, hetaryl-, and alkylboronic acids were studied. Optimization experiments with silyl-protected 2-bromo-O(6)-methylinosine led to the identification of [PdCl(2)(dcpf)]/K(3)PO(4) in 1,4-dioxane as the best conditions for these reactions (dcpf=1,1'-bis(dicyclohexylphosphino)ferrocene). Attempted O(6)-demethylation, as well as the replacement of the C-6 methoxy group by amines, was unsuccessful, which led to the consideration of Pd-cleavable groups such that C-C cross-coupling and O(6)-deprotection could be accomplished in a single step. Thus, inosine 2-chloro-O(6)-allylinosine was chosen as the substrate and, after re-evaluation of the cross-coupling conditions with 2-chloro-O(6)-methylinosine as a model substrate, one-step C-C cross-coupling/deprotection reactions were performed with the O(6)-allyl analogue. These reactions are the first such examples of a one-pot procedure for the modification and deprotection of purine nucleosides under C-C cross-coupling conditions.
研究了 O(6)-烷氧基-2-溴代和 2-氯代肌苷衍生物与芳基、杂芳基和烷基硼酸的 CC 交叉偶联反应条件。用硅保护的 2-溴代-O(6)-甲基肌苷进行优化实验，确定[PdCl(2)(dcpf)]/K(3)PO(4)在 1,4-二氧六环中是这些反应的最佳条件（dcpf=1,1'-双(二环己基膦基)二茂铁）。尝试 O(6)-脱甲基化以及 C-6 甲氧基被胺取代均不成功，这促使人们考虑使用 Pd 可裂解基团，以便可以在单个步骤中完成 C-C 交叉偶联和 O(6)-脱保护。因此，选择肌苷 2-氯-O(6)-烯丙基肌苷作为底物，在重新评估了 2-氯-O(6)-甲基肌苷作为模型底物的交叉偶联条件后，用 O(6)-烯丙基类似物进行了一步 C-C 交叉偶联/脱保护反应。这些反应是在 C-C 交叉偶联条件下对嘌呤核苷进行修饰和脱保护的一锅法的首例实例。
