Single-step formation of structurally defined bicyclic peptides via S(N)Ar cyclization.
[structure: see text]. A solid-phase methodology for macrocyclization via an S(N)Ar reaction has been developed for the unambiguous formation of bicyclic peptidic compounds in a single cyclization step. The cyclization strategy involves the reaction of a 3,5-dihydroxybenzoyl group with two nitrofluorobenzoyl moieties. The symmetry of the dihydroxy aromatic ring results in a single product, and the remaining nitro groups are subsequently reduced to anilines and acylated.
Kohn
W D
WD
Eli Lilly & Company, Sphinx Laboratories, 840 Memorial Drive, Cambridge, Massachusetts 02139, USA. kohn_wayne@lilly.com
Zhang
L
L
Weigel
J A
JA
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D015195:Drug Design; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
D001643:Bridged Bicyclo Compounds; D062385:Hydroxybenzoates; D010455:Peptides