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DOI: 10.1055/s-0030-1258425
Expedient Synthesis of 1,3-Substituted Benzene Peptidomimetics
Publikationsverlauf
Publikationsdatum:
08. Februar 2011 (online)
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Abstract
A synthetic route for replacing the central amino acid in the tripeptide Thr-Ala-Val (TAV) with a 1,3-substituted benzene ring was developed. l-Threonine was introduced into the benzene ring by a Grignard reaction with protected l-threoninal, where the nature of the side-chain protecting group was found to be of utmost importance. Subsequently, l-valine was introduced by a copper-mediated amination. Overall, the tripeptide analogue was obtained in six steps with an overall yield of 18%. An orthogonal protecting group strategy allowed attachment of the tripeptide analogue to a solid support and subsequent preparation of the corresponding pentapeptide analogue. Both compounds were tested in a plasma stability assay, showing improved stability compared to their peptide counterparts.
Key words
amino acids - peptides - Grignard reaction - nucleophilic aromatic substitution - copper
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