title: An expeditious route to fluorinated rapamycin analogues by utilising mutasynthesis.
abstract: Rapamycin is a drug with several important clinical uses. Its complex structure means that total synthesis of this natural product and its analogues is demanding and lengthy. A more expeditious approach is to utilise biosynthesis to enable the generation of otherwise synthetically intractable analogues. In order to achieve this, rules governing biosynthetic precursor substrate preference must be established. Through determining these rules and synthesising and administering suitable substrate precursors, we demonstrate the first generation of fluorinated rapamycin analogues. Here we report the generation of six new fluororapamycins.
authors.affiliation: School of Chemical Sciences, University of East Anglia, Norwich, UK. r.goss@uea.ac.uk
authors.forename: Rebecca J M
authors.initials: RJ
authors.lastname: Goss
authors.forename: Simon
authors.initials: S
authors.lastname: Lanceron
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Deb Roy
authors.forename: Simon
authors.initials: S
authors.lastname: Sprague
authors.forename: Mohammed
authors.initials: M
authors.lastname: Nur-E-Alam
authors.forename: David L
authors.initials: DL
authors.lastname: Hughes
authors.forename: Barrie
authors.initials: B
authors.lastname: Wilkinson
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Moss
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D005461:Fluorine / Q000737:chemistry*; D008968:Molecular Conformation; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000903:Antibiotics, Antineoplastic; D005461:Fluorine; D020123:Sirolimus