Peptide enolization

These peptide enolates could also be used as excellent nucleophiles in palladium-catalyzed allylic alkylations. Reactions of numerous dipeptides (e.g. 263) with different allylic substrates (e.g. 264) and [AllPdClja as catalyst delivered (S,/f)-configured peptides with y,5-unsaturated side chains (265), usually in high yields and diastereoselectivities (equation 69). 

If the Claisen rearrangement is carried out with peptide allylic esters, the transfer of an allylic side chain to the a-position of the C terminal amino acid results in a modification of the peptide chain. This concept is comparable to the alkylations of peptide enolates described by Seebach et al. [93]. If it is possible to carry out the rearrangement not only with amino acids but also with peptide esters, the question arises if it is possible to transfer the chiral information from the peptide chain to the new chiral center formed during the rearrangement process, prohahly via some peptide metal enolate complexes. 

For pioneering work on the alkylation of peptidic enolates, see (a) Seebach, D. (1988) Angew. Chem., 100, 1685-1715 Angew. Chem., Int Ed. Engl, 27, 1624-1654j (b) Seebach, D., Beck, A.K., and Studer, A. (1995) in Modern Synthetic Methods, vol. 7 (eds B. Ernst and C. Leumann), Helvetica Chimica Acta/VCH, Basel/Weinheim, pp. 1-178 and references therein (c) For a personal review entitled How we drifted into peptide chemistry and where we have arrived at, see Seebach, D., Kimmerlin, T, Sebesta, R., Campo, M.A., and Beck, A.K. (2004) Tetrahedron, 60, 7455-7506. 

The smooth conversion of the enol acetate (151) into an A -acyl derivative (152) under extremely mild conditions points to the high acylating capacity of these esters. This cleavage of isoxazolium salts is also caused by other anions of carboxylic acids, and thus they can be readily converted to reactive enol esters. A very convenient and specific synthesis of peptides due to Woodward et is based on... 

Fig. 3 Protonation states, isomerism and mesomerism of the HBI chromophore (p-hydroxybenzi-lidene-imidazolinone). The chromophore is shown in its most stable Z ( cw ) conformation, conventionally associated to a 0° value of the dihedral angle t, while the E ( trans ) conformation corresponds to t = 180°. For model compound HBDI (4 -hydroxy-benzylidene-2,3-dimethyl-imidazolinone), Ri = R2 = CH3, for chromophore in GFP, Ri, and R2 stand for the peptidic main chains toward N-terminus and C-terminus, respectively, (a) Possible protonation states of HBI (a) neutral, (b) anionic, (c) enolic, (d) cationic, and (e) zwitterionic. (b) Two resonance structures of the anionic form of HBI...

BASE-CATALYZED ENOLIZATION OF OXAZOLONES FORMED FROM ACTIVATED PEPTIDES... 

Fig. 6.25. Simplified mechanism of two degradation reactions between peptides and reducing sugars occurring in solids, a) Maillard reaction between a side-chain amino (or amido) group showing the formation of an imine (Reaction a), followed by tautomerization to an enol (Reaction b) and ultimately to a ketone (Reaction c). Reaction c is known as the Amadori rearrangement (modified from [8]). b) Postulated mechanism of the reaction between a reducing sugar and a C-terminal serine. The postulated nucleophilic addition yields an hemiacetal (Reaction a) and is followed by cyclization (intramolecular condensation Reaction b). Two subsequent hydrolytic steps (Reactions c and d) yield a serine-sugar conjugate and the des-Ser-peptide...

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