Abstract
This work describes the synthesis of thirteen cyclooctapeptides dicarba-analogues of Somatostatin, containing L- or D-allylglycine (Agl) residues at the termini of the peptide chain, through on resin Ring Closing Metathesis (RCM) of the linear octapeptides. We investigated the influence of the stereochemistry of some strategic amino acids on the propensity to give the cyclic compounds in mild conditions (refluxing DCM). Systematic individual replacement of Phe6,7,11 residues with the corresponding enantiomers, strongly favoured the ring closure by conventional heating. The yield of the cyclic products was strictly correlated to the position of this amino acid on the peptide chain. In particular substitution of Phe6 by Tyr in peptides which did not give the cyclic compounds, allowed the ring formation. The effect of the phenolic −OH function of Tyr side chain on the proximity of the terminal Agl residue was studied by NMR techniques. All the linear precursors gave cyclic somatostatin dicarba-analogues, in good to high yields and in short reaction times, by microwave-assisted RCM, performed with the 2nd generation Grubbs catalyst. The unsaturated dicarba-tether resulted in a mixture of E and Z stereoisomers in a variable ratio, depending on the sequence and the cyclization method. The E isomer was largely the most abundant in all but one the described product.
Original language | English |
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Pages (from-to) | 365-372 |
Number of pages | 8 |
Journal | Chemical Engineering and Processing: Process Intensification |
Volume | 122 |
DOIs | |
Publication status | Published - Dec 1 2017 |
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Keywords
- Cyclooctapeptides
- Dicarba-analogues of somatostatin
- Micro-wave assisted peptide synthesis
- Microwaves-driven RCM
- Ring closing metathesis (RCM)
ASJC Scopus subject areas
- Chemistry(all)
- Chemical Engineering(all)
- Energy Engineering and Power Technology
- Process Chemistry and Technology
- Industrial and Manufacturing Engineering
Cite this
Synthesis of dicarba-cyclooctapeptide Somatostatin analogs by conventional and MW-assisted RCM : A study about the impact of the configuration at Cα of selected amino acids. / Pratesi, Alessandro; Stazzoni, Samuele; Lumini, Marco; Sabatino, Giuseppina; Carotenuto, Alfonso; Brancaccio, Diego; Novellino, Ettore; Chinol, Marco; Rovero, Paolo; Ginanneschi, Mauro; Papini, Anna Maria.
In: Chemical Engineering and Processing: Process Intensification, Vol. 122, 01.12.2017, p. 365-372.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis of dicarba-cyclooctapeptide Somatostatin analogs by conventional and MW-assisted RCM
T2 - A study about the impact of the configuration at Cα of selected amino acids
AU - Pratesi, Alessandro
AU - Stazzoni, Samuele
AU - Lumini, Marco
AU - Sabatino, Giuseppina
AU - Carotenuto, Alfonso
AU - Brancaccio, Diego
AU - Novellino, Ettore
AU - Chinol, Marco
AU - Rovero, Paolo
AU - Ginanneschi, Mauro
AU - Papini, Anna Maria
PY - 2017/12/1
Y1 - 2017/12/1
N2 - This work describes the synthesis of thirteen cyclooctapeptides dicarba-analogues of Somatostatin, containing L- or D-allylglycine (Agl) residues at the termini of the peptide chain, through on resin Ring Closing Metathesis (RCM) of the linear octapeptides. We investigated the influence of the stereochemistry of some strategic amino acids on the propensity to give the cyclic compounds in mild conditions (refluxing DCM). Systematic individual replacement of Phe6,7,11 residues with the corresponding enantiomers, strongly favoured the ring closure by conventional heating. The yield of the cyclic products was strictly correlated to the position of this amino acid on the peptide chain. In particular substitution of Phe6 by Tyr in peptides which did not give the cyclic compounds, allowed the ring formation. The effect of the phenolic −OH function of Tyr side chain on the proximity of the terminal Agl residue was studied by NMR techniques. All the linear precursors gave cyclic somatostatin dicarba-analogues, in good to high yields and in short reaction times, by microwave-assisted RCM, performed with the 2nd generation Grubbs catalyst. The unsaturated dicarba-tether resulted in a mixture of E and Z stereoisomers in a variable ratio, depending on the sequence and the cyclization method. The E isomer was largely the most abundant in all but one the described product.
AB - This work describes the synthesis of thirteen cyclooctapeptides dicarba-analogues of Somatostatin, containing L- or D-allylglycine (Agl) residues at the termini of the peptide chain, through on resin Ring Closing Metathesis (RCM) of the linear octapeptides. We investigated the influence of the stereochemistry of some strategic amino acids on the propensity to give the cyclic compounds in mild conditions (refluxing DCM). Systematic individual replacement of Phe6,7,11 residues with the corresponding enantiomers, strongly favoured the ring closure by conventional heating. The yield of the cyclic products was strictly correlated to the position of this amino acid on the peptide chain. In particular substitution of Phe6 by Tyr in peptides which did not give the cyclic compounds, allowed the ring formation. The effect of the phenolic −OH function of Tyr side chain on the proximity of the terminal Agl residue was studied by NMR techniques. All the linear precursors gave cyclic somatostatin dicarba-analogues, in good to high yields and in short reaction times, by microwave-assisted RCM, performed with the 2nd generation Grubbs catalyst. The unsaturated dicarba-tether resulted in a mixture of E and Z stereoisomers in a variable ratio, depending on the sequence and the cyclization method. The E isomer was largely the most abundant in all but one the described product.
KW - Cyclooctapeptides
KW - Dicarba-analogues of somatostatin
KW - Micro-wave assisted peptide synthesis
KW - Microwaves-driven RCM
KW - Ring closing metathesis (RCM)
UR - http://www.scopus.com/inward/record.url?scp=85014130948&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014130948&partnerID=8YFLogxK
U2 - 10.1016/j.cep.2017.02.005
DO - 10.1016/j.cep.2017.02.005
M3 - Article
AN - SCOPUS:85014130948
VL - 122
SP - 365
EP - 372
JO - Chemical Engineering and Processing - Process Intensification
JF - Chemical Engineering and Processing - Process Intensification
SN - 0255-2701
ER -