Amides conformations

Fig. 8. Rephcation. 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 <7 -amide conformer cis-Z that isomeri2es to the more stable trans- acnide Z. The rephcative process is cataly2ed by the reaction product Z (also referred to as the template). First, a termolecular complex XYZ is formed from X, Y, and Z.

In conjunction with our studies on the synthetic utility of amide enolates (35,36), we have postulated that the high (Z)-stereoselection observed in the deprotonation of dialkylamides is a consequence of ground state allylic strain considerations (37), which strongly disfavor amide conformation B (Scheme 8), and consequently the associated transition state T (Scheme 7) for deprotonation, to give ( )-enolates. 

Lepisto M, Sellergren B. Discrimination between amino-acid amide conformers by imprinted polymers. J Org Chem 1989 54 6010-6012. 

The planar cis-amide conformation in the seven-membered lactam already can impose some strain on the ring and thus increase its polymerizability. 

All four five-membered proline ring constraints in the CTP are, however, essential for stabilizing any m-amide-bond conformers (132). A single substitution of N-methyl-L-alanine, or the six-membered homolog, L-pipecolic acid, destabilizes all the cm-amide conformers of c[Pro-pro-Pro-pro] and only the all-trans-amide tttt conformers were populated (see Fig. 9). 

Recently, Marshall and coworkers have reported on the particular structural behavior of azaproline (azPro) derivative Ac-azPro-NHMe (Fig. 8.3) which tends to form an eight-member hydrogen bond (i — i + 1) in a typical / -turn conformation without introducing any steric bulk. It stabilizes a cis-amide bond whereas proline favors a seven-member H-bond (i + 2 — i) with a trans-amide conformation (y-turn) (Fig. 8.3) [27]. Additional N-methylation decreases the energy difference between cis- and trans-azPro conformers and hence severely perturbs the /fturn conformation [28]. In nonproline derivatives, permethylation inverted the tendency since calculation at the B3LYP/6-31G level showed that the ds-Ac-azAla-NHMe was 1.36 kcal mol-1 more stable than the trans-amide conformer, whereas trans-Ac-azAla-NHMe was favored by 1.24 kcal mol-1 [32]. 

Table 11.3 Values of and (// dihedral angles for the trans-amide conformers of Ac-Pro -OMe with Pro = Pro, (4R)-Hyp, (4R)-FPro and (4S)-FPro [34,39],...

Among other proline analogs such as 13-17 shown in Fig. 11.4, NMR analysis of the N-acetyl derivatives of 13-16 in neutral solutions did not reveal any significant difference in the trans/cis ratio compared with N-acetyl-proline except for 5-oxo-proline (15) which exhibits an exclusive trans-amide conformation [63]. However, when replacing proline in Ala-Pro-pNA with Aze (13) and Pip (14) the cis-amide content was 20% and 13%, respectively, compared with 6% for the Pro-peptide. Rates of CTI were accelerated 14.5- and 49-fold relative to the Pro-peptide [64]. 

Fig. YI.9 General framework of dipeptide mimics with a trans-amide conformation X and Y represent possible heteroatoms in the fused rings which can vary in the size and bear additional substitutents to mimic the amino acid side-chains. A stereocontrol of the ring-fusion center Z is difficult to achieve.

Scheme 10.1 (a) resonance forms in aryl amides illustrating the restricted rotation of the Ar-C(0)NH bond because of the partial double bond character and (b) examples of hydrogen bonding motifs stabilising particular aryl amide conformers. 

C. S. Rao, A. J. Ratcliffe, and B. Fraser-Reid, Pentenyl mannosides in the synthesis of N-acylmannopyranosyl amides Conformational analysis of intermediates, J. Chem. Soc., Perkin Trans., 1 (1993) 1207-1211. 

Crab chitin, and chitin from the diatom Thalassiorira fluviatilis dissolves in hexafluoro-2-propanol far-u.v. and c.d. spectra of solutions, gels, and films of the chitin have been recorded. A trans-amide conformation and intermolecu-lar hydrogen bonding are proposed as the important determinants of the observed solid state c.d. spectra. 

Although the use of water as a solvent for the reaction between cyclopenta-diene (4.8) and chiral acrylamide 4.21 led to the usual rate enhancement, it did not have a dramatic effect on either the endo/exo ratio or diastereoselec-tivity. In retrospect, the modest diastereoselectivity is not really surprising since the chiral center is quite remote from the olefin in the preferred trans-amide conformation. 

Changes in the frequencies, half-widths and intensities of the Raman bands of protein chemical groups mainly give information about changes in secondary protein structure (amide conformation region, C-C stretching vibration), while modifications... 

In contrast, frans-amide conformation was strongly favored when aryl substituents were introduced directly at the backbone nitrogen (Fig. 5c) [56]. Similarly, hydroxyl and alkoxyl substituents were demonstrated to direct the amide bond into a frans-conformation (Fig. 5d) [57, 58]. 

A recent example of the application of RR to a structural problem will serve to illustrate its utility as a comparative tool. Figure 6 shows two peptide fragments in different conformations. This compound models the peptide A l-42, a constituent of the amyloid plaques characteristic of Alzheimer s disease. Rotational resonance MAS NMR was used in a qualitative fashion by Costa and co-workers to determine whether the amide conformation in the solid state was ds or trans From previous... 

A tertiary amide 483b (Scheme 16.99) is a better activating group than a secondary amide 483a, most likely because the former is not conformationally biased and allows access to the cw-amide conformation required for the [4-1-2] cycloaddition [200]. 

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