Abstract
The present study describes an efficient access to enantioenriched pyrimidines’ derivatives from readily available Boc-AA-NH2 and β-enaminones. This strategy allows the synthesis of a large variety of chiral pyrimidines (18 examples) with good yields from the chiral pool. In the case of peptide isosteres, this procedure proved to be highly stereoretentive and paves the way to the construction of C-terminal modified peptidomimetics as illustrated in the synthesis of two original pyrimidines containing pseudo-dipeptides.
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Abbreviations
- AA:
-
Amino acid
- Ac:
-
Acetyl
- Ala:
-
Alanine
- Bn:
-
Benzyl
- Boc:
-
Tert-butoxycarbonyl
- Cbz:
-
Carboxybenzyl
- DCM:
-
Dichloromethane
- Glu:
-
Glutamine
- Gly:
-
Glycine
- Ile:
-
Isoleucine
- KHMDS:
-
Potassium bis(trimethylsilyl)amide
- Met:
-
Methionine
- MS:
-
Molecular sieve
- Phe:
-
Phenylalanine
- Pro:
-
Proline
- PyBOP:
-
Benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate
- THF:
-
Tetrahydrofuran
- Tyr:
-
Tyrosine
- Val:
-
Valine
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Funding
The project was supported by funds from the ENSCM, the CNRS, the Tunisian Ministry of Higher Education and Scientific Research, and the Erasmus Mundus Programme KITE (S.S. mobility grant).
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Sahtel, S., Maamer, C.B., Besbes, R. et al. Straightforward synthesis of various chiral pyrimidines bearing a stereogenic center adjacent to the C-2 position, including C-terminal peptide isosteres. Amino Acids 54, 1519–1526 (2022). https://doi.org/10.1007/s00726-022-03192-y
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DOI: https://doi.org/10.1007/s00726-022-03192-y