1 research outputs found
Biaryl-Bridged Macrocyclic Peptides: Conformational Constraint via Carbogenic Fusion of Natural Amino Acid Side Chains
A general method for constraining peptide conformations
via linkage of aromatic sidechains has been developed. Macrocyclization
of suitably functionalized tri-, tetra- and pentapeptides via Suzuki–Miyaura
cross-coupling has been used to generate side chain to side chain,
biaryl-bridged 14- to 21-membered macrocyclic peptides. Biaryl bridges
possessing three different configurations, meta–meta, meta–ortho,
and ortho–meta, were systematically explored through regiochemical
variation of the aryl halide and aryl boronate coupling partners,
allowing fine-tuning of the resultant macrocycle conformation. Suzuki–Miyaura
macrocyclizations were successfully achieved both in solution and
on solid phase for all three sizes of peptide. This approach constitutes
a means of constraining peptide conformation via direct carbogenic
fusion of side chains of naturally occurring amino acids such as phenylalanine
and tyrosine, and so is complementary to strategies involving non-natural,
for example, hydrocarbon, bridges