Carbohydrates are found on cell-surfaces of most organisms and viruses, on proteins, and even on bioactive small molecules (eg. macrolide antibiotics). Complex carbohydrate-mediated interactions play a crucial role in biology and medicine, influencing cell signalling, immune responses, and disease pathways. Despite this, there are not many carbohydrate-based drugs (apart from nucleoside analogues), and this is due to their excessive hydrophilicity (or low lipophilicity expressed as logP). Deoxyfluorination (OH to F) has been employed to modify the logP, with polyfluorination leading to significant increases. Upon substitution of OH to F, hydrogen bond donating funtional groups are removed, which are important for binding to proteins. As such, the removal of these OH-groups should be limited. In this project, we wish to address various approaches to further affect the logP by exploring a variety of yet unexplored dihalogenated carbohydrates: geminal difluorination, geminal and vicinal chloro-fluoro substitution patterns. This leads to the modification (and introduction) of a range of different interactions which, depending on the particular position of halogenation, will lead to increase or decrease of logP compared to mono- and difluorinated analogues. A series of fluorine and chlorine containing carbohydrate derivatives will be synthesized in order to measure their lipophilicity with an NMR-based published procedure; the main goal is to understand the
connection between the chemical structure of these molecules and their physical properties (lipophilicity in particular), with possible implications in medicinal chemistry and drug discovery. The data that will be collected are mostly chemical reaction data (temperature, reaction time, pressure, mass, yields, spectroscopic data,...) and they will be stored on paper and/or digitally.