GIRK channels (G protein mediated inwardly-rectifying potassium ion channels) have been shown to regulate the electrical activity of several cell types including neurons, cardiac atrial myocytes, and β-pancreatic cells. As such, the malfunction of GIRK channels has also been implicated in disorders such as neuropathic pain, drug addiction, and cardiac arrhythmias. Falcatin A is a myrsinane diterpenoid that possesses inhibitory activity against GIRK channels with an IC50 value of 2.5 ± 0.2 uM. We hypothesize that the 5/7/6 carbocyclic framework of the natural product could be constructed in a single step through a combination of hydrogen bonding, hydrogen atom transfer, and photoredox catalysis to bring together two complex fragments in a convergent coupling strategy, allowing for the rapid and efficient synthesis of falcatin A and analogues. The synthesis and studies of falcatin A and its analogues could potentially provide some insight into the modulation of GIRK channels. Herein, we describe our synthetic progress toward the total synthesis of falcatin A.

Progress toward the total synthesis of falcatin A

2019 Spring National Meeting

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