title: The synthesis of gemcitabine.
abstract: Gemcitabine is a fluorinated nucleoside currently administered against a number of cancers. It consists of a cytosine base and a 2-deoxy-2,2-difluororibose sugar. The synthetic challenges associated with the introduction of the fluorine atoms, as well as with nucleobase introduction of 2,2-difluorinated sugars, combined with the requirement to have an efficient process suitable for large scale synthesis, have spurred significant activity towards the synthesis of gemcitabine exploring a wide variety of synthetic approaches. In addition, many methods have been developed for selective crystallisation of diastereomeric (including anomeric) mixtures. In that regard, the 2-deoxy-2,2-difluororibose sugar is one of the most investigated fluorinated carbohydrates in terms of its synthesis. The versatility of synthetic methods employed is illustrative of the current state of the art of fluorination methodology for the synthesis of CF2-containing carbohydrates, and involves the use of fluorinated building blocks, as well as nucleophilic and electrophilic fluorination of sugar precursors.
authors.affiliation: Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK; Dextra Laboratories Ltd, The Science and Technology Centre, Earley Gate, Whiteknights Road, Reading RG6 6BZ, UK.
authors.forename: Kylie
authors.initials: K
authors.lastname: Brown
authors.affiliation: Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Dixey
authors.affiliation: Dextra Laboratories Ltd, The Science and Technology Centre, Earley Gate, Whiteknights Road, Reading RG6 6BZ, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Weymouth-Wilson
authors.affiliation: Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK. Electronic address: bruno.linclau@soton.ac.uk.
authors.forename: Bruno
authors.initials: B
authors.lastname: Linclau
mesh_terms: D002241:Carbohydrates / Q000737:chemistry; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry; D054879:Halogenation; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D013237:Stereoisomerism; D000093542:Gemcitabine
chemical_list: D002241:Carbohydrates; D003841:Deoxycytidine; D005461:Fluorine; D000093542:Gemcitabine
keywords: Fluorinated nucleoside; Fluorination; Fluorosugar; Gemcitabine; Nucleobase introduction