Synthesis of 6-deoxy-6-fluorosugars

• Main Author: Roig, Ricard
• Published: University of Leicester 2006
• Subjects: 547
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.697336

This project is based on the chemical synthesis of fluorosaccharide end-products, which could be used potentially as substrates for the combinatorial biosynthesis of novel complex structures like antibiotics. Although fluorine is the most abundant halogen in the earth's crust, the incidence of fluorinated natural products is extremely low. There are no examples of fluorosaccharide end-product molecules in nature, so novel architecture will result from their incorporation within oligosaccharides or complex antibiotics. Introducing fluorine into pharmaceutical compounds can increase the biological activity and stability to metabolism. Enantiomerically enriched and racemic 6-fluoro and racemic 6,6-difluoro analogues of amicetose and rhodinose have been synthesized successfully using different and scaleable strategies from commercially available starting materials. The equilibria between furanoses and pyranoses favoures the smaller rings, due to the inductive electron withdrawing effects of fluorine, so it was necessary to use protection to deliver pyranoses exclusively. Two very efficient new fluorinating methods have been developed, one with in situ cis/trans-isomerisation of a double bond with a mixture of TBAI and TBAF, and another one with high regioselective epoxides ring-opening with a mixture of KHF2 and TBAF. In addition to the synthesis of 6-deoxy-6-fluorosugars, a long lived difluoroenol was discovered and fully characterised, methanolysis rates and solvent isotope effect were measured.