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Solid‐Phase Synthesis of Biaryl Cyclic Peptides Containing a 3‐Aryltyrosine
Author(s) -
Afonso Ana,
Cussó Olaf,
Feliu Lidia,
Planas Marta
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200832
Subject(s) - chemistry , iodobenzene , borylation , combinatorial chemistry , solid phase synthesis , cyclic peptide , suzuki reaction , combinatorial synthesis , organic chemistry , stereochemistry , palladium , peptide , catalysis , aryl , biochemistry , alkyl
A concise and efficient solid‐phase synthesis of biaryl cyclic peptides containing a Phe–Tyr or a Tyr–Tyr linkage has been accomplished. The key steps include a Miyaura borylation of a resin‐bound 3‐iodotyrosine and a microwave‐assisted Suzuki–Miyaura reaction for the formation of the macrocycle. First, the feasibility of the solid‐phase Miyaura borylation of a 3‐iodotyrosyltripeptide was established. Then, the Suzuki–Miyaura reaction was applied to the cross‐coupling of linear 3‐boronotyrosine‐containing peptidyl resins with iodobenzene and with halogenated aromatic amino acids. Finally, this methodology was extended to the synthesis of biaryl cyclic peptides through the preparation of a linear peptidyl resin containing both the required boronate and halogenated derivatives, followed by a microwave‐assisted Suzuki–Miyaura macrocyclization.