Conformational amides

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.

The treatment of 3-benzoyl-2-phenylisoxazolidine with strong base generated an aldehyde and a ketimine <74X1121). Under these conditions dimethyl 2-a-methoxyisoxazolidine-3,3-dicarboxylic acid (186) produced isoxazoline-2-carboxylic acid. Reaction of the monomethyl amide (187) gave the corresponding isoxazoline-2-carboxamide (Scheme 60). CD was used in the conformational studies <79X213). 

Amides 1-4 all adopt conformations in wiiich a i-butyl group has an axial-like position and, as a result, a non-chair conformation of the six-membered ring. Comment on the origin of this stmctural effect. 

The similarity between the cryptands and the first of these molecules is obvious. Compound 7 7 is a urethane equivalent of [2.2.2]-cryptand. The synthesis of 7 7 was accomplished using a diacyl halide and l,10-diaza-18-crown-6 (shown in Eq. 8.13). Since amidic nitrogen inverts less rapidly than a tertiary amine nitrogen, Vogtle and his coworkers who prepared 7 7, analyzed the proton and carbon magnetic resonance spectra to discern differences in conformational preferences. Compound 7 7 was found to form a lithium perchlorate complex. 

Rotation about single bonds and conformational changes can be studied. Amides constitute a classic example. Because of the partial double bond character of the carbon-nitrogen bond as a consequence of the contribution of 2 to the electronic structure, there is an energy barrier to rotation about this bond. 

FIGURE 5.2 The peptide bond is shown in its usnal trans conformation of carbonyl O and amide H. The atoms are the oi-carbons of two adjacent amino acids joined in peptide linkage. The dimensions and angles are the average valnes observed by crystallographic analysis of amino acids and small peptides. The peptide bond is the light gray bond between C and N. (Adapted from Ramachandran, G. A., ct ai, 1974. Biochimica Biophysica Acta 359 298-302.)... 

FIGURE 6.2 The amide or peptide bond planes are joined by the tetrahedral bonds of the ff-carbon. The rotation parameters are p and Ip. The conformation shown corresponds to clockwise rotation as viewed from Starting from 0°, a rotation of 180° in the clockwise direction ( + 180°) is equivalent to a rotation of 180° in the counterclockwise direction (—180°). (truing G s)... 

A set of low-energy conformers has been provided for alanine (R=CH3) tetramer (terminated at both ends by amide functionality). For each conformer, identify each of the a carbons and measure the (j) and v(/ dihedral angles (see table below). 

Two of the three single bonds involved in each unit are flexible, and their detailed conformation dictates overall polypeptide structures and (ultimately) function. The amide bond is generally assumed to be rigid. Why (See also Chapter 10, Problem 1.)... 

Larger polymers are known as proteins. Aside from the amide linkages, the polymer chain is very flexible, giving rise to the possibility of an enormous number of different conformers. It is nothing short of remarkable, therefore, that proteins rapidly fold into a single conformation. Very strong forces must be at work. 

Boat conformation (cyclohexane), steric strain in, 118 Boc (fcJrf-butox carbonyl amide). 

The synthesis of key intermediate 6 begins with the asymmetric synthesis of the lactol subunit, intermediate 8 (see Scheme 3). Alkylation of the sodium enolate derived from carboximide 21 with allyl iodide furnishes intermediate 26 as a crystalline solid in 82 % yield and in >99 % diastereomeric purity after recrystallization. Guided by transition state allylic strain conformational control elements5d (see Scheme 4), the action of sodium bis(trimethylsilyl)amide on 21 affords chelated (Z)-enolate 25. Chelation of the type illustrated in 25 prevents rotation about the nitrogen-carbon bond and renders... 

The photoelectron spectra of 11 //-dibenz[Z>,e]azepine52 and 5//-dibenz[6,/]azepine53 have been measured. The results for the latter suggest that in the gas phase, the molecule has an almost planar conformation. A comparison of the photoelectron spectra of 5-methyl- and 5-acetyl-5 H-dibenz(7 ,/]azepine supports the important contribution of the amide mesomer to the latter.32... 

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