Source: School of Pharmaceutical Sciences
Written by: School of Pharmaceutical Sciences
Edited by: Wang Dongmei

The research group of Prof. Honggen Wang from the School of Pharmaceutical Sciences of Sun Yat-sen University, in collaboration with Prof. Wenhui Hu and Dr. Xin Zhao from the Guangzhou Institutes of Biomedicine and Health (CAS), has developed a novel synthetic methodology for the late-stage modification of 3-Pinanamine, a potent influenza virus A natural product derivative. This work was published in Organic Letters on Aug 4, 2014 (Org. Lett., 2014, 16, 4288–4291).

3-Pinanamine, derived from a-pinene, is prevalent as motif in medicinal chemistry and asymmetric synthesis. For instance, the group of Prof. Wenhui Hu previously discovered that 3-pinanamine exhibits as potent anti-influenza virus A activity as amantadine. However, due to its structural complexity, the synthetic modification of 3-Pinanamine represents a long-lasting challenge. No derivatives of 3-pinanamine at the d position has ever been synthesized. In line with the pursuit of novel 3-pinanamine based anti-influenza virus A agent, the research groups developed a novel direct functionalization of 3-pinanamine by using a palladium-catalyzed C(sp3)–H activation logic. Good substrate scope and functional group tolerance were observed. The research represents a good example of late-stage C-H functionalization of functional molecules and a rare example of direct functionalization of aliphatic amine at the remote d position.

The collection of 3-Pinanamine using this protocol and their biological evaluation against influenza virus A is currently underway.

This work was supported by a Start-up Grant from Sun Yat-sen University, National Science Foundation of China (81302648), the Guangzhou Science and Technology Plan (201300000052) and funding from the State Key Laboratory of Respiratory Disease.