Synthesis of 6,6'-dideoxy-6,6'-difluorotrehalose

ABSTRACT Trehalose is a disaccharide consisting of two glucose units connected by an α,α-1,1 linkage. It is classified as an osmolyte and is present in high concentrations in tardigrades, which are the first animals to survive in the vacuum of outer space. Recent research has suggested that trehalose is responsible for greatly stabilizing cellular proteins and allowing them to withstand harsh environmental conditions, including extreme heat and cold, desiccation, pressure, and even radiation. Scientific literature has also reported the effectiveness of fluorinating osmolytes to improve the stability of enzymes in extreme environmental conditions. It has been speculated that fluorinated trehaloses may be able to provide greater protection for proteins than unmodified trehaloses. The 6,6'-dideoxy-6,6'-difluorotrehalose (7) was synthesized in the lab via a series of alcohol protections and deprotections of trehalose and analyzed using 1H NMR, 13C NMR, COSY, HSQC, and HMBC. Compounds (2) - (6) were analyzed using 1H NMR (and 13C NMR when available). It is expected that fluorinated trehalose, if proven to exhibit enhanced properties versus regular trehalose, will open up new possibilities ranging from therapeutic treatments for astronauts in space to preservatives for biological proteins. The difluorotrehalose analogue will be tested using fluorescence and circular dichroism spectroscopy for its interaction with melittin in the hopes that its ability to stabilize proteins can be compared to that of regular trehalose.