A general method for preparation of N-Boc-protected or N-Fmoc-protected α,β-didehydropeptide building blocks and their use in the solid-phase peptide synthesis
| Autor: | Marek Lisowski, Grzegorz Wołczański |
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| Rok vydání: | 2018 |
| Předmět: |
Stereochemistry
Peptide 010402 general chemistry 01 natural sciences Biochemistry chemistry.chemical_compound Residue (chemistry) Structural Biology Drug Discovery Peptide synthesis Trifluoroacetic acid Molecular Biology Tribromide Solid-Phase Synthesis Techniques Pharmacology chemistry.chemical_classification Dipeptide Molecular Structure 010405 organic chemistry Organic Chemistry General Medicine Dipeptides 0104 chemical sciences PyBOP chemistry Molecular Medicine Pyridinium |
| Zdroj: | Journal of peptide science : an official publication of the European Peptide Society. 24(8-9) |
| ISSN: | 1099-1387 |
| Popis: | N-(tert-butyloxycarbonyl) or N-(9-fluorenylmethoxycarbonyl) dipeptides with C-terminal (Z)-α,β-didehydrophenylalanine (∆Z Phe), (Z)-α,β-didehydrotyrosine (∆Z Tyr), (Z)-α,β-didehydrotryptophan (∆Z Trp), (Z)-α,β-didehydromethionine (∆Z Met), (Z)-α,β-didehydroleucine (∆Z Leu), and (Z/E)-α,β-didehydroisoleucine (∆Z/E Ile) were synthesised from their saturated analogues via oxidation of intermediate 2,5-disubstituted-oxazol-5-(4H)-ones (also known as azlactones) with pyridinium tribromide followed by opening of the produced unsaturated oxazol-5-(4H)-one derivatives in organic-aqueous solution with a catalytic amount of trifluoroacetic acid or by a basic hydrolysis. In all cases, a very strong preference for Z isomers of α,β-didehydro-α-amino acid residues was observed except of the ΔIle, which was obtained as the equimolar mixture of Z and E isomers. Reasons for the (Z)-stereoselectivity and the increased stability of the aromatic α,β-didehydro-α-amino acid residue oxazol-5-(4H)-ones over the corresponding aliphatic ones are also discussed. It is the first use of such a procedure to synthesise peptides with the C-terminal unsaturated residues and a peptide with 2 consecutive ΔPhe residues. This approach is very effective especially in the synthesis of peptides with aliphatic α,β-didehydro-α-amino acid residues that are difficult to obtain by other methods. It allowed the first synthesis of the ∆Met residue. It is also more cost-effective and less laborious than other synthesis protocols. The dipeptide building blocks obtained were used in the solid-phase synthesis of model peptides on a polystyrene-based solid support. Peptides containing aromatic α,β-didehydro-α-amino acid residues were obtained with PyBOP or TBTU as a coupling agent with good yields and purities. In the case of aliphatic α,β-didehydro-α-amino acid residues, a good efficiency was achieved only with DPPA as a coupling agent. |
| Databáze: | OpenAIRE |
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