Total synthesis of rapamycin.
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.
Ley
Steven V
SV
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. svl1000@cam.ac.uk
Tackett
Miles N
MN
Maddess
Matthew L
ML
Anderson
James C
JC
Brennan
Paul E
PE
Cappi
Michael W
MW
Heer
Jag P
JP
Helgen
Céline
C
Kori
Masakuni
M
Kouklovsky
Cyrille
C
Marsden
Stephen P
SP
Norman
Joanne
J
Osborn
David P
DP
Palomero
María A
MA
Pavey
John B J
JB
Pinel
Catherine
C
Robinson
Lesley A
LA
Schnaubelt
Jürgen
J
Scott
James S
JS
Spilling
Christopher D
CD
Watanabe
Hidenori
H
Wesson
Kieron E
KE
Willis
Michael C
MC
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
D000970:Antineoplastic Agents; D001688:Biological Products; D007166:Immunosuppressive Agents; D020123:Sirolimus