The tricyclic diterpene fungal metabolite (+)-Pleuromutilin was isolated in 1951 by Kavanagh and co-workers from several species of basidiomycetes and has been found noteworthy for antibacterial activity through a novel mode of action involving binding to the prokaryotic ribosome.¹ With the promising effect against the resistant bacteria to antibiotics due to its unique mechanism of action, its intricate skeleton including rare 8-membered ring of tricyclo-[5.4.3.01,8]-tetradecane has intrigued the synthetic chemistry community. To construct the interesting tricyclic framework of pleuromutilin, there have been various approaches. We have reported previously the total synthesis of subernosene with tricycle-[4.3.2.01,5]- undecane via vinyl radical tandem cyclization from the cyclopentene containing appropriate dibutyne tethers.² Furthermore, the tendency of cyclization were also shown with larger ring system from 5- to 8-membered ring.³ Based on those results, we envisioned that the core structure of pleuromutilin would be obtained in one-pot from cyclooctene with requisite dibutyne tethers in similar way. Along the way, we observed unusual ring closure by radical rearrangement derived from steric and conformational factors. In this presentation we will discuss the mechanism of the reaction and eventual construction of the framework of pleuromutilin consisting of tricyclo-[5.4.3.01,8]-tetradecane. References 1. (a) Hogenauer, G. Eur. J. Biochem. 1975, 52, 93, (b) Tang, Y. Z.; Liu, Y. H.; Chen, J. X. Mini-Rev. Med. Chem., 2012, 12, 53. (c)Kirst, H. A. Expert Opin. Ther. Pat., 2012, 22, 15. 2. Lee, H. Y.; Kim, B. G. Org. Lett. 2000, 2, 1951 3. Lee, H.-Y.; Lee, S.; Kim, B. G.; Bahn, J. S. Tetrahedron Lett. 2004, 45, 7225