Amidation trans

A peptoid pentamer of five poro-substituted (S)-N-(l-phenylethyl)glycine monomers, which exhibits the characteristic a-helix-like CD spectrum described above, was further analyzed by 2D-NMR [42]. Although this pentamer has a dynamic structure and adopts a family of conformations in methanol solution, 50-60% of the population exists as a right-handed helical conformer, containing all cis-amide bonds (in agreement with modeling studies [3]), with about three residues per turn and a pitch of 6 A. Minor families of conformational isomers arise from cis/trans-amide bond isomerization. Since many peptoid sequences with chiral aromatic side chains share similar CD characteristics with this helical pentamer, the type of CD spectrum described above can be considered to be indicative of the formation of this class of peptoid helix in general. 

An interesting reaction ensues when the intermediate synthetic precursor (65) to synthon 60 is heated with phenylenediamine. The reaction can be rationalized as involving initial enamine-imine formation (66), followed by intramolecular attack on the ester carbonyl groups resulting in carbamate formation (67), which carbamate undergoes intramolecular trans-amidation to give urea 66. Other scenarios can be proposed and defended, but the net result is formation... 

The strained ds-amide complex undergoes a fast isomerisation to the trans-amide species 85 which exposes two hydrogen-bonding binding sites suitable to interact with two new molecules of reactants 82 and 83. Such molecules can then... 

Description of band Cis-amide absorption bands Trans-amide absorption bands... 

One precaution should be kept in mind for n -methyl amino acids. N-methylatlon of the peptide linkage results in the energy of the usual trans amide becoming comparable to that of the cis ( ). The trans to cis transformation at a point in the peptide backbone results in a significMt conformational change. This possibility must be considered in interpreting results based on incorporation of N -methyl amino acids. 

And most importantly for a discussion of the replacement of amide bonds by fluoroolefin isosteres, the cis and trans amide bonds have different hydration shells [43,85]. The role of solvation and desolvation is understood to be crucial not only in amide bond isomerization but also in peptide transport generally. 

A careful stereochemical analysis has led to the conclusion that for all of the different aminoacyl groups to be able to react in the same way at the peptidyltransferase site and to all generate trans amide linkages, the torsion angles < ) and q/ of the resulting peptide must be approximately those of an a helix.388 Thus, the peptide emerging from the ribosome exit tunnel may be largely helical. 

However, in some systems the redistribution of monomer segments may result from other reactions, such as trans-esterification, trans amidation or trans-etherification. Consider, e.g., a solution of living polyglycols... 

Pauling and Corey recognized a second stable conformation of polypeptide chains —the extended chain or /3-pleated sheet (Figure 25-13). In this conformation the chains are fully extended with trans amide configurations. In this arrangement the distance is maximized between adjacent amino-acid... 

Fig. 8. Replication. The amino adenosine X and the pentafluorophenyl ester Y form a hydrogen-bonded dimer XY, prior to reaction between the amine and the activated ester groups (shown in the circle). The reaction product is a at-amide conformer cis-Z that isomerizes to the more stable trans-amide Z. The replicative process is catalyzed by the reaction product Z (also referred to as the template). First, a termolecular complex XYZ is formed from X, Y, and Z.

H NMR spectroscopy revealed that methyl cis-3H,9aH-2-acetyl- and 2-ferf-butoxycarbonylperhydropyrido[l,2-a]pyrazine-3-carboxylates exist a ca. 3.3 1 and ca. 1 1 mixtures of cis- and trans-amide rotamers, respectively, in CDCI3 solution (08SL702). 

The is-olefin was prepared as a trans-amide bond replacement. A number of compounds incorporating substituents to mimic both natural and unnatural amino acid sidechains were prepared by adapting chemistry developed by Ibuka for the synthesis of Zs-olefin peptide isosteres (see Scheme l).40,41 The key step involved anti-SN2 displacement of vinyl mesylate 8 by boron trifluoride-activated cuprate addition. Compounds containing butyl, propyl, and benzyl substituents at the allylic positions to mimic the aj and sidechains produced potent FTase inhibitors (Table 4). 

Crombie, L. Jones, R. C. F. Haigh, D. Trans-amidation reactions of /i-lactarns a synthesis of ( )-dihydroperiphylline. Tetrahedron Lett. 1986, 27, 5151-5154. 

Poly Proline Helices. Poly proline (PP) displays some unusual structural properties as it is die only naturally occuring tertiary amide found in polypeptides. The inability of this residue to act as a hydrogen-bond donor leads to two types of extended helical structures, neither of which resembles the a helix. The first, called PP I, is a right-handed helix which possesses cis amide bonds (left-handed helix with trans amide bonds ( d = 180°). Both occupy a fairly limited region of < >,y space. The two forms interconvert slowly over time. 

Thus, the trans-aminocydohexanecarboxyhc acid 3c was prepared by all three microorganisms in very high e.e. (87-99%), whereas the intermediate amides were formed in moderate e.e. In contrast, five-membered trans-amide lb was obtained in very high enantiopurity, but not so its acid [34]. The high enantiomeric purity of the remaining trons-nitriles la and 3a is remarkable in view of the extent of conversion (38 and 24%, respectively).This can be attributed to the reportedly high enantioselectivity of the nitrile hydratase from R. erythropolis A4 for the transformation of ( )-la to lb at the least [40]. 

Figure 9 Computer models of (a) the cyclic correlate based on 12 monomeric units of (2S,4fi)-4-amino-5-oxopyrrolidine-2-carboxylic acid. The idealized backbone i r torsion angles are 120°, 120°, respectively, (b) The nanotubular structure resulting from vertical self-assembling of the cyclic correlate through intermolecular N-FI O = C Fl-bonds that involve the trans amides (62). The black and white atoms are oxygens and hydrogens, respectively.

Crisma M, Moretto A, Toniolo C, Kaczmarek K, Zabrocki J. First rigid peptide foldamers with an alternating cis-trans amide sequence. An oligomeric building block for the construction of new helices, large-ring cyclic correlates, and nanombes. Macromolecules 2001 34 5048-5052. 

Work of Davies and Thomas (503) casts doubt on the generalization that trans amides form linear polymers and cis amides form cyclic dimers. They have found that both trichloroacetamide and its iV-methyl derivative form cyclic... 

Piperazine-2,5-dithiones, thio analogues of cyclic dipeptides, have been shown to have a flattened boat configuration (1643), and infrared spectroscopic studies indicate that in the trans tautomer (120) the C-N bond has a more pronounced double bond character than that of the trans amide tautomer (1644). 

The acidity of cis amide groups (of small and medium lactams) is much lower than that of the trans amide groups in the corresponding linear polymer. As soon as polymer amide groups are formed, the concentration of lactam anions is lowered due to the equilibrium... 

However, the total concentration of anions is increased appreciably (Table 8) and an increasing fraction of anions arises from trans amides whereas the concentration of lactam anions decreases steeply. It has been estimated [164], that the formation of 2.5% of polymer lowers the concentration of lactam anions by 30% whereas the total concentration of amide anions doubles. 

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