Volatile Anesthetic Sevoflurane Precursor 1,1,1,3,3,3-Hexafluoro-2-Propanol (HFIP) Exerts an Anti-Prion Activity in Prion-Infected Culture Cells.

Prion disease is a neurodegenerative disorder with progressive neurologic symptoms and accelerated cognitive decline. The causative protein of prion disease is the prion protein (PrP), and structural transition of PrP from the normal helix rich form (PrPC) to the abnormal ß-sheet rich form (PrPSc) occurs in prion disease. While so far numerous therapeutic agents for prion diseases have been developed, none of them are still useful. A fluorinated alcohol, hexafluoro isopropanol (HFIP), is a precursor to the inhalational anesthetic sevoflurane and its metabolites. HFIP is also known as a robust α-helix inducer and is widely used as a solvent for highly aggregated peptides. Here we show that the α-helix-inducing activity of HFIP caused the conformational transformation of the fibrous structure of PrP into amorphous aggregates in vitro. HFIP added to the ScN2a cell medium, which continuously expresses PrPSc, reduced PrPSc protease resistance after 24-h incubation. It was also clarified that ScN2a cells are more susceptible to HFIP than any of the cells being compared. Based on these findings, HFIP is expected to develop as a therapeutic agent for prion disease.

Stereochemical Investigation of the Products of the Photoinduced Perfluoroalkylation-Dimerization of Anthracene.

The photoinduced perfluoroalkylation of anthracene has been shown to provide 9,9',10,10'-tetrahydro-10,10'-diperfluoroalkyl-9,9'-bianthracenes in over 70% yields, each perfluoroalkyl iodide producing three diastereomers. The structures of all three diastereomers (cis,cis, cis,trans, and trans,trans isomers) have been elucidated by both NMR and X-ray crystallographic analyses. Most notably, an X-ray crystallographic analysis has revealed that the trans,trans diastereomer having the two trifluoromethyl groups in 10,10'-positions adopts a 74° twisted relationship of the two dihydroanthracene rings. Furthermore, each of the two trans,trans isomers 2a,b has been shown to exist as a mixture of new types of atropisomers and the energy barrier for the interconversion of the two atropisomers has been estimated to be 12 kcal/mol by variable-temperature NMR analysis.