Amide trans configuration

Cyclic dipeptides, especially when N-alkylated, undergo extremely fast epimerization (79JA1885). For example, cyclo(L-Pro-L-Phe) is rapidly converted to its diastereomer, cyclo(D-Pro-L-Phe) (80% conversion), by treatment with 0.5 N NaOH at 25°C for 15 min. This diastereomer is the one in which the proline residue has epimerized and not the more activated phenylalanine. CNDO/2 calculations seem to provide a rationale for this. It is not yet completely clear why such base-catalyzed epimerizations of piperazinediones are so easy the conformation of the molecule may play a role in this (79MI1). It is also worth noting that even in linear peptides, rm-amides of N-alkyl-amino acids, which consist of s-trans and s-cis rotamers of almost equal energy, are more prone to racemization than the sec-amides, which exist only in the s-trans configuration. Of course, the amide functions of piperazine-2,5-diones are obliged to assume the s-cis conformation. 

The occurrence of the ds-isomer in a tertiary amide bond. 19-21 N-Alkylated amides normally exhibit a mixture of cisltrans-isomers that equilibrate in the order of seconds (AG+ 18-20 kcal-mol-1). The situation is shifted from a pure trans configuration in a secondary (—NHCO—) peptide bond to an equilibrium of both isomers of similar energy upon N-alkylation the percentage of ds-isomer depends upon both the solvent and the sequence. The ds-peptide bond 22-27 is observed between the N-alkylated and the preceding residues in the chain. It is evident that Xaa-Pro peptides will behave similarly. 

There are several other points to notice about the a helix shown in Figure 25-11. The amide groups are planar and normally retain the stable trans configuration in the helical structure bond lengths and bond angles are... 

Figure 25-12 Ball-and-stick model of a peptide unit showing the coplanarity of the CNCC atoms of the amide linkage, here in the trans configuration, and the possibility of rotation about the C-C and N-C bonds.

At low temperature (-78 °C) deprotonation with the bulky silyl amide KHMDS runs under kinetic control - enolization takes place regio-and stereoselectively at the terminal methyl group of ketone 4. The sterically less hindered enolate is transformed to enol triflate 22, which has all-trans configuration. 

The chemistry of the pungent compounds of pepper has been under study since the isolation of piperine in 1820. Piperine was shown to be a piperidide of piperic acid, and had the trans. trans configuration. The three other possible isomers were soon postulated, and they were named isopiperine (cis.trans). isochavicine (trans. cis) and chavicine (cis.cis) even before they were synthesized. The assignment of the isomeric configuration starts from the amide end. 

Steric energies for the three possible conformations of the two amide systems in macrocycle 13 were determined by MM+ method <2002J(P2)2078>. Depicted trans-trans-configuration with total force field energy 8.1-12.3 kcal mol-1 is less stable when compared to trans-cis-and cis-cis-conformations (2.9-6.3 and 6.3 kcal mol-1, respectively). 

Method C), in the case of silylated amides (R, R" = SiXs) in diethyl ether at -20°C, leads to disilylaryltriazenes (9) (7) in good yields (for individual compounds, cf. Table I). The latter compounds, formed according to Eq. (8), exist in the cis as well as the trans configuration. In fact, the formation of cu-triazene is favored with decreasing reaction temperature, whereas tram-triazene formation is favored with increasing reaction temperature. ... 

Simanouchi and Mizushima (1858) 2-7-1 A flat ribbon Emphasized trans configuration of amide groups... 

These two polymers are characterized by a stable trans-configuration of the amide bond and by a high barrier of the rotation around the aryl carbon bond. The directions of rotational axes in all the chain units almost coincide. As a result, according to Tsvetkov the entire macromolecule acquires the shape of a crankshaft (Fig. 1). In the case of PBA, the retardation of rotation of the units may be also caused by a transfer of conjugation in the carbonyl-nitrogen system via a phenylene ring. 

Figure 2.2. A representative dipeptide made up from L-a-amino acids, in the extended conformation with the amide bond in the trans configuration.

Myoglobin is an extremely compact molecule with very little empty space, accommodating only a small number of water molecules within the overall molecular dimensions of 4.5 x 3.5 x 2.5 nm. All of the peptide bonds are planar with the carbonyl and amide groups in trans configurations to each... 

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