2- pyridine, conformational analysis

The recognition that short chain / -peptides can form regular secondary structures initially came from detailed conformational analysis of y9 -peptides 1 and 66 (which incorporates a central (2S,3S)-3-amino-2-methylbutanoic acid residue) by NMR in pyridine-d5 and CD3OH [10, 103, 164] and homooUgomers (as short as four residues) of trons-2-amino-cyclohexanecarboxyhc acid (trans-ACHC) (e.g. hex-amer 2 for the (S,S) series) by NMR and X-ray diffraction [6, 126, 159]. 

Detailed NMR conformational analysis of y -peptides 139-141 (Fig. 2.35) in pyri-dine-d5 revealed that y-peptides as short as four residues adopt a 2.6-hehcal fold stabilized by H-bonds between C=0 and NH +3 which close 14-membered pseudocycles [200, 201]. The 2.614-helical structure of a low energy conformer of y-hex-apeptide 141 as determined from NMR measurements in pyridine-d5 [200], is shown in Fig. 2.36A and B). Determination of the structure of y" -peptides in CD3OH was hampered by the much lower dispersion of the diasterotopic H-C(a) protons compared to their dispersion in pyridine-d5. However, the characteristic and properly resolved i/ir-2 NOE crosspeacks between H-C(y) and NH +2 in the NH/H-C(y) region of the ROESY spectrum were an indication that the 2.6-helical structure is at least partially populated in CD3OH. 

Conformational analysis of some octahydroimidazo[l,2- ]pyridine derivatives have been investigated by NMR studies <2000JOC3683, 2002JOC4951, 2000JOC7208>. For example, compounds 235-237 are depicted in Scheme 65 in their preferred conformations. The anomeric carbon in such compounds is prone to epimerization, favoring a trans ring junction. 

As mentioned in connection with the benzoyl derivatives of five-membered heterocycles, conformational analysis of benzoyl derivatives of pyridine suffers from the indetermination connected with the necessity of simultaneously assigning N,0-cis/trans populations and conformer structures from experimental results. The all-planar conformations should be excluded... 

The conformational analysis of the perhydro-imidazo[l,5-n]pyridines (465) (Section VI), the perhydro-oxazolo[3,4-a]pyridines (466) (Section VII), and the perhydrothiazolo[3,4-a]pyridines (467) (Section VIII) may best be considered together since the conformational preferences of these systems are dominated by the generalized anomeric effect [83MI1 ... 

The earliest studies on the IR spectra of crown ethers and their complexes were carried out by Pederson (B-78MI52101). Since then IR spectroscopy has been applied a number of times to solve structural problems in crown ether chemistry including ion pair interactions and conformational analysis (B-79MI52103). A low frequency vibration of the cation within the macrocycle has been identified which is dependent on the cation but not on the solvent (214 cm for Na -dibenzo[18]crown-6 in both DMSO and pyridine). This is in contrast to the frequency of cation vibration within a solvent cage, which for Na is 202 cm in... 

Haginoya, N., Kobayashi, S., Komoriya, S., Yoshino, X, Suzuki, M., Shimada, X, Watanabe, K., Hirokawa, Y, Fumgori, X, Nagahara, X. Synthesis and conformational analysis of a non-amidine factor Xa inhibitor that incorporates 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 binding element. 7. Med. Cherrr 2004,47(21), 5167-5182. 

The conformational analysis of several linear proline-containing hormones has been considerably aided by 1 3C nmr studies. The ratio of cis- and trans-isomers and the spin lattice relaxation times of thyrotropin-releasing factor or hormone (TRF or TRH), L-pyro-glutamyl-L-histidyl-L-prolinamidc, in deuterium oxide, deuterated dimethyl sulfoxide and deuterated pyridine have been determined... 

The chemistry of both of these perhydro systems was discussed as a part of a wider review <90AHC(49)193>. Particular attention was paid to the synthesis and utilization of perhydro-oxazolo[3,2-a]pyridines and to the conformational analysis of the [3,4-a] fused system. 

Nuclear Magnetic Resonance Spectroscopy.—As noted above, conformational analysis of bicyclo[3.3.1]nonanes is still a topic of considerable interest. A variable-temperature n.m.r. analysis now provides the first case in which the boat-chair-chair-boat equilibrium is directly observed in the amines (17) and (18). In a related case, re-examination of the acetal (19) suggests that the preferred conformation involves a chair carbocyclic ring and a boat heterocyclic ring. This conclusion was made by n.m.r. analysis, using lanthanide shift reagents, by a study of nuclear Overhauser effects, and by measurement of relaxation times of protons. Details have been reported for other 3-azabicyclo[3.3.1]nonanes, and the non-additivity of substituent effects on chemical shifts in 9-thiabicyclo[3.3.1]non-2-enes has been analysed. Both and n.m.r. data have been reported for a series of 9-borabicyclo[3.3.1]non-anes and their pyridine complexes. 

A vivid example of the application of conformational analysis for unsubstituted 2,2 -bipyryl was reported by Kelly (01ACR514). In the free bipyridyl, the pyridine rings adopted a twisted conformation with a large flexibility around the pivot bond, brake off in 226. Upon complexation the system adopted a much more rigid sy -planar conformation that blocked the triptycyl rotation at low temperature, brake on 227. 

Pyridine-d5 was found to show the most favorable solvent-induced changes of the chemical shifts for the three compounds in so far as a first-order analysis of the 60-MHz spectra was possible, the observed splittings gave no indication for solvent-induced, conformational changes. 

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