title: Total synthesis of rapamycin.
abstract: For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. svl1000@cam.ac.uk
authors.forename: Steven V
authors.initials: SV
authors.lastname: Ley
authors.forename: Miles N
authors.initials: MN
authors.lastname: Tackett
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Maddess
authors.forename: James C
authors.initials: JC
authors.lastname: Anderson
authors.forename: Paul E
authors.initials: PE
authors.lastname: Brennan
authors.forename: Michael W
authors.initials: MW
authors.lastname: Cappi
authors.forename: Jag P
authors.initials: JP
authors.lastname: Heer
authors.forename: Céline
authors.initials: C
authors.lastname: Helgen
authors.forename: Masakuni
authors.initials: M
authors.lastname: Kori
authors.forename: Cyrille
authors.initials: C
authors.lastname: Kouklovsky
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Marsden
authors.forename: Joanne
authors.initials: J
authors.lastname: Norman
authors.forename: David P
authors.initials: DP
authors.lastname: Osborn
authors.forename: María A
authors.initials: MA
authors.lastname: Palomero
authors.forename: John B J
authors.initials: JB
authors.lastname: Pavey
authors.forename: Catherine
authors.initials: C
authors.lastname: Pinel
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Robinson
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schnaubelt
authors.forename: James S
authors.initials: JS
authors.lastname: Scott
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Spilling
authors.forename: Hidenori
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kieron E
authors.initials: KE
authors.lastname: Wesson
authors.forename: Michael C
authors.initials: MC
authors.lastname: Willis
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D020123:Sirolimus / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D007166:Immunosuppressive Agents; D020123:Sirolimus