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Synlett 2014; 25(13): 1843-1846
DOI: 10.1055/s-0034-1378330
DOI: 10.1055/s-0034-1378330
letter
A One-Pot Saponification–Coupling Sequence Suitable for C-Terminus Peptide Elongation Using Lithium Carboxylates
Further Information
Publication History
Received: 08 April 2014
Accepted after revision: 23 May 2014
Publication Date:
08 July 2014 (online)
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Abstract
An efficient procedure has been developed for the saponification of common peptide esters, followed by straightforward coupling of the lithium carboxylate. Adding some water to the reaction medium gave faster saponification and did not interfere with the coupling reagent. As peptide chemistry constitutes a major application of the amidation reaction, amino acid substrates were chosen for this study, monitoring both yields and epimerization of the peptides obtained.
Supporting Information
- Analytical data, copies of NMR spectra, and experimental preparations of all compounds are available online at http://www.thieme-connect.com/products/ejournals/ journal/10.1055/s-00000083.
- Supporting Information
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References and Notes
- 1a El-Faham A, Albericio F. Chem. Rev. 2011; 111: 6557
- 1b Montalbetti C, Falque V. Tetrahedron 2005; 61: 10827
- 1c Peptides: Chemistry and Biology . Sewald S, Jakubke H.-D. Wiley-VCH Verlag GmbH & Co; Weinheim: 2002. and references cited therein
- 2 Evans DA. Aldrichimica Acta 1982; 15: 23
- 3 Valnot JY, Maddaluno J In The Chemistry of Organolithium Compounds. Vol. 2. Rappoport Z, Marek I. Wiley; Hoboken, NJ: 2006: 555
- 4 Griehl C, Weight J, Jeschkeit H. J. High. Res. Chromatogr. 1994; 17: 700
- 5 Polyak F, Lubell WD. J. Org. Chem. 1998; 63: 5937
- 6 Goodreid JD, Duspara PA, Bosch C, Batey RA. J. Org. Chem. 2014; 79: 943
- 7 Achatz D, Lang MA, Völkl A, Fehlhammer WP, Beck WZ. Anorg. Allg. Chem. 2005; 631: 2339
- 8 Vasudevan A, Ji Z, Frey RR, Wada CK, Steinman D, Heyman HR, Guo Y, Curtin ML, Guo J, Li J, Pease L, Glaser KB, Marcotte PA, Bouska JJ, Davidsen SK, Michaelides MR. Bioorg. Med. Chem. Lett. 2003; 13: 3909
- 9a For a review, see: Llanes GarcıaA. L. Synlett 2007; 1328
- 9b Dunetz JR, Xiang Y, Baldwin A, Ringling J. Org. Lett. 2011; 13: 5048
- 10a Carpino LA. J. Am. Chem. Soc. 1993; 115: 4397
- 10b Carpino LA, El-Faham A, Albericio F. Tetrahedron Lett. 1994; 35: 2279
- 11 General Procedure for the Formation of Carboxylates and Subsequent Coupling Reaction: To a solution of Cbz-Ala-Phe-OMe (0.3 g, 0.81 mmol) in dioxane (2 mL) at r.t. were added LiOH (25 mg, 1 mmol) and H2O (0.35 mL, 19.44 mmol, 24 molar equiv). Stirring at r.t. and monitoring by HPLC showed complete saponification and a clear, homogeneous solution generally after 3 h. Amino acid H-AA-OMe, HCl (0.9 mmol) and HATU (0.463 g, 1.22 mmol) were added and the mixture was stirred at r.t. until completion, generally 4 h. The diastereomeric purity was measured at this stage, before isolation and purification. After concentration in vacuo, the residue was purified by silica gel chromatography with a mixture of CH2Cl2–EtOAc as eluent to afford the pure tripeptide as a white solid