Dimerization of Pyramidalized 3,4,8,9‐Tetramethyltetracyclo [4.4.0.0^3,9.0^4,8]dec‐1(6)‐ene to a Hydrocarbon Featuring Four Cyclohexane Rings in Boat Conformations

Abstract

The synthesis, chemical trapping, and dimerization of a highly pyramidalized alkene is reported. Its dimer is a unique nonacycle featuring three planar cyclobutane rings, four cyclopentane rings, and four cyclohexane rings in boat conformations. The X-ray diffraction analysis showed a H-H distance between the flagpole hydrogen atoms of 1.999 and a separation of 2.619 between the two flagpole carbon atoms. The three cyclobutane rings of the dimer were thermally stable.

X-ray Crystal Structures of the Influenza M2 Proton Channel Drug-Resistant V27A Mutant Bound to a Spiro-Adamantyl Amine Inhibitor Reveal the Mechanism of Adamantane Resistance

“…19,20 Overall, the V27A mutation is becoming more prevalent in circulating populations of influenza, 18 so there has been interest in designing drugs to target it. [21][22][23][24][25][26] Here we present X-ray crystal structures of the drug-resistant V27A mutant of M2 bound to a spiro-adamantyl amine inhibitor, using both M2 and M2 constructs for crystallization trials. Spiro-adamantyl amine was developed by molecular dynamics simulation-directed design and was able to inhibit the conductance of protons in both the V27A mutant and the WT channel in two electrode voltage clamp (TEVC) assays using Xenopus oocytes, with an IC 50 of 0.3 μM against the V27A channel and an IC 50 of 18.7 μM against the WT channel (compare to IC 50 = 15.7 μM for amantadine against the WT channel).…”