Comparative study of methods to couple hindered peptides
- 1 September 1992
- journal article
- research article
- Published by Wiley in International Journal of Peptide and Protein Research
- Vol. 40 (3-4) , 282-293
- https://doi.org/10.1111/j.1399-3011.1992.tb00303.x
Abstract
A comparative study of modern coupling reactions involving Boc‐protected amino acid derivatives and dipeptides with N‐terminal α,α–dialkylation and N‐methylation was carried out. The coupling reactions were run using either equimolar amounts of the amino and activated carboxyl components or an excess of the activated carboxyl component. Yields of the target tripeptide Boc‐Phe‐Xaa‐Phe‐OBzl (Xaa = (NMe)Ala, (NMe)Alb, or (NMe)αAc5c) were compared. Less than 10% of the product was obtained from methods utilizing pivaloyl mixed anhydride, pentafluorophenyl ester or acyl fluoride activation when Xaa = (NMe)Aib and (NMe)αcAc5c. At room temperature, significant yields of these two products were obtained from reactions which utilized an excess of the HBTU reagent (O‐benzotriazol‐1‐yl‐N,N,N′,N′‐tetramethyluronium hexafluorophosphate), the PyBroP reagent (bromo‐tris‐pyrrolidino‐phosphonium hexafluorophosphate) or Boc‐Phe‐NCA (Boc‐protected phenylalanine N‐carboxyanhydride). Moreover, the Boc‐Phe‐NCA method was superior when used over a prolonged reaction time or at elevated temperature.Keywords
This publication has 14 references indexed in Scilit:
- tert-Butyloxycarbonyl and benzyloxycarbonyl amino acid fluorides. New, stable rapid-acting acylating agents for peptide synthesisThe Journal of Organic Chemistry, 1991
- Easy coupling of Aib with the reagents PyBOP® and PyBroPPublished by Springer Nature ,1991
- PyBOP® and PyBroP: Two reagents for the difficult coupling of the α,α-dialkyl amino acid, Aib.Tetrahedron, 1991
- New coupling reagents in peptide chemistryTetrahedron Letters, 1989
- Bop‐Cl mediated cyclization of a linear precursor of virginiamycin S. Contra indication for using HOBt as racemization suppressorBulletin des Sociétés Chimiques Belges, 1988
- N,N'‐bis(2‐oxo‐3‐oxazolidinyl) phosphinic chloride (BOP‐Cl); a superb reagent for coupling at and with iminoacid residuesInternational Journal of Peptide and Protein Research, 1987
- The Practice of Peptide SynthesisPublished by Springer Nature ,1984
- Synthesis of Cyclosporine. Part II. Synthesis of Boc‐D‐Ala‐MeLeu‐MeLeu‐MeVal‐OH, a part of the peptide sequence of cyclosporine, by different strategic ways and synthesis of its isomers Boc‐D‐Ala‐MeLeu‐D‐MeLeu‐MeVal‐OH, Boc‐D‐MeLeu‐DMeVal‐OH, and Boc‐D‐Ala‐MeLeu‐MeLeu‐D‐MeVal‐OH as reference compoundsHelvetica Chimica Acta, 1983
- A SERIES OF LYSYLDIPEPTIDE DERIVATIVES FOR RACEMIZATION STUDIES IN PEPTIDE SYNTHESISInternational Journal of Peptide and Protein Research, 1979
- Reactifs de couplage peptidique I (1) - l'hexafluorophosphate de benzotriazolyl N-oxytrisdimethylamino phosphonium (B.O.P.)Tetrahedron Letters, 1975