Peptide coupling reagent

Example Character of R COOH Character of R2NH2 Dehydr. agent r coni/r2 application Yield (%) Reference 

3 Dipeptide Amino thioester DCC Peptide thioacid 93 20060L823 

6 Cyclopentane-carboxylic acid Methyl glycinate TBTU Peptides 98 2005HGA1711 

7 Aminosugar acid Aminosugar HBTU Oligosaccharide mimic 89 2005AGE2096 

8 Arenoxyacetic acid Methyl glycinate DCC Heteroditopic receptors 71 2006CJC58 

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Williams, A., and Ibrahim, I.A. (1981) A mechanism involving cyclic tautomers for the reaction with nucleophiles of the water-soluble peptide coupling reagent l-ethyl-3-(3-dimethyla-minopropyl) carbo-diimide (EDC)./. Am. Chem. Soc. 103, 7090-7095. 

B Castro, JR Dormoy, G Evin, B Castro. Peptide coupling reagents IV (1) — benzotriazole V-oxytrisdimethylamino phosphonium hexafluorophosphate (B.O.P.) Tetrahedron Lett 1219, 1975. 

V Dourtoglou, J-C Ziegler, B Gross. L hexafluorophosphate de O-benzotriazolyl-AW-tetramethyluronium hexafluorophosphate a new and efficient peptide coupling reagent. Tetrahedron Lett 1269, 1978. 

J Coste, D Le-Nguyen, B Castro. PyBOP A new peptide coupling reagent devoid of toxic by-product. Tetrahedron Lett 31, 205, 1990. 

B Castro, J-R Dormoy, G Evin, C Selve. Peptide coupling reagents. Part VII. Mechanism of the formation of active esters of hydroxybenzotriazole in the reaction of carboxylate ions on the BOP reagent for peptide coupling. A comparison with Itoh s reagent. J Chem Res (S) 82, 1977. 

J Coste, E Frerot, P Jouin, B Castro. Oxybenzotriazole free peptide coupling reagents for N-methylated amino acids. Tetrahedron Lett 32, 1967, 1991. 

LA Carpino, D Sadat-Aalaee, HG Chao, RH DeSelms. ((9-Fluorenylmethyl)oxy)car-bonyl (FMOC) amino acid fluorides. Convenient new peptide coupling reagents applicable to the FMOC/ferf-butyl strategy for solution and solid-phase syntheses. J Am Chem Soc 112, 9651, 1990. 

LA Carpino, EME Mansour, A El-Faham. Bis(BOC) amino acid fluorides as reactive peptide coupling reagents. J Org Chem 58, 4162, 1993. 

LA Carpino, A El-Faham. Tetramethylfluoroformidinium hexafluorophosphate a rapid-acting peptide coupling reagent for solution and solid phase peptide synthesis. J Am Chem Soc 117, 5401, 1995. 

LA Carpino, H Imazumi, A El-Faham, FJ Ferrer, C Zhang, Y Lee, BM Foxman, P Henklein, C Hanay, C Miigge, H Wenschuh, J Klose, M Beyermann, M Bienert. The uronium/guanidinium peptide coupling reagents finally the true uronium salts. Angew Chem Inti Edn 41, 442, 2002. 

P Li, J-C Xu. New and highly efficient immonium type peptide coupling reagents synthesis, mechanism and application. Tetrahedron 56, 4437, 2000. 

The so-called Weinreb amides (or Af-methoxy-A-methylamides) are versatile building blocks in organic synthesis . Their preparation can be accomplished by coupling carboxylic acids and Af,0-dimethylhydroxylamme. The majority of the methods reported use peptide coupling reagents such as chloroformates , BOP , DCC and others "" or phosphonic derivatives ". These reactive reagents are expensive in some cases, and the removal of their excess (and/or the removal of byproducts) from the reaction mixtures may be difficult. Additional purification of the reaction product is often required. 

Scheme 9 HOBt Incorporated into Peptide Coupling Reagents 21 221...

Saponification of the ester is followed by coupling with 8 using a peptide coupling reagent. 

HATU is the most powerful yet most expensive peptide coupling reagent on the market. It is preferentially used for the coupling of sterically hindered amino acids or during the synthesis of complex peptides (21) without the addition of HOBt. However, due to its high price, amino acids for which high incorporation... 

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