Conformations of cyclic molecules

M. Billeter, A, E. Howard, 1. D. Kuntz, and P. A. Kollman,/. Am. Chem. Soc., 110, 8383 (1988), A New Technique to Calculate Low-Energy Conformations of Cyclic Molecules Utilizing the Ellipsoid Algorithm and Molecular Dynamics Application to 18-Crown-6. 

There are many other examples of rearrangements, isomerizations, and equilibrations that lend themselves to study by NMR spectroscopy. This technique is used to study changes in conformations of cyclic molecules, proton-exchange reactions, and biochemical processes. 

Eliel, E.L., Wilen, S.H. and Doyle, M.R, Eds., Configuration and conformation of cyclic molecules, in Basic Organic Stereochemistry, Wiley-Interscience, New York, 2001, 421 pp. 

The preceding prediction rules are largely restricted to acyclic compounds. But there is also a considerable need for parameter sets enabling the spectroscopist to calculate I3C chemical shifts of conformationally defined cyclic molecules, especially of the cyclohexane type. Methyl-group effects in methylcyclohexanes (100,101) that are to be added to the basic value for cyclohexane itself (8 = 27.3) are listed in Table 29. Analogous methyl-group parameters in tetralins and tetra-hydroanthracenes have been reported (403). 

Undoubtedly, the vicinal groups play a fundamental role in the outcome of this reaction, especially with the sugars, where the favored conformation of the molecule at equilibrium is controlled at the outset by groups that determine whether the molecule exists as a cyclic or acyclic structure. The deamination of cyclic and acyclic amino sugar derivatives by nitrous acid will be considered in turn. 

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. 

Ascidiacyclamide (14), a cytotoxic, cyclic peptide, was isolated from an unidentified species of ascidian [40], The absolute configuration was determined and the structure confirmed by total synthesis [41]. An X-ray crystal structure was carried out [42] and further X-ray crystallographic studies determined the conformation of the molecule in the solid- and solution-states [43]. 

The viscosity of a linear polyelectrolyte solution depends on the conformation of the molecules, which in turn is affected by intramolecular electrostatic interactions between charged segments located along the polymer backbone, but the interactions in systems of charged polyelectrolytes are still far from being understood. The study on the solution property of cyclic polyelectrolyte is of interest, since the chain expansion of a cyclic... 

Determination of the relative stability of many other substituted cyclohexane stereoisomers can be done in a similar manner. However, examples in which there are complications due to 1,3-diaxial interactions between groups or examples in which the rings are substituted with polar groups, whose dipoles interact, are much more complicated. Recently, computer programs have been developed that enable the most stable conformation of many molecules, cyclic and noncyclic, to be determined. These molecular mechanics calculations can provide the most stable shape of even quite complex molecules. 

The conformational behavior of cyclic molecules is conveniently discussed separately from that of acyclic molecules. Ring closure indeed imposes conformational constraints and limitations not existing in linear systems. 

B. Equilibrium Cyclic Concentration Method for Studying the Conformations of Chain Molecules... 

The first application of the equilibrium cyclic concentration method to measure precisely the average conformations of chain molecules in a polymer was for poly-(dimethylsiloxane) 16,18-20, 36). In Fig. 4, Kx values for a bulk equilibrate at 383 K (19) are compared with the corresponding values for a solution equilibrate (in toluene at a siloxane concentration of 224 g dm ) [Refs. 18,20) and with theo-... 

Among other molecules in this class are symmetrically substituted cyclic trans olefins of the type depicted in Fig. 10. All conformations of these molecules are asymmetric the reason, as in the examples already discussed, is that the plane of the trans olefin unit remains at all times perpendicular to the average plane of the — (CH2) CHR(CH2) — fragment. Given a sufficiently large ring size (n> 3), internal rotation about the single bonds of the olefinic moiety interconverts all conformational enantiomers. An example of this type is the meso diepoxide derived from trans, trans, transA,5,9-cyclododecatriene. ... 

Acyclic molecules can readily minimize strain simply by changing conformation. There is less freedom to make large changes of conformation in cyclic molecules and so the incidence of strain is much more... 

Formation and trapping of the lithium enolate gave only the E silyl enol ether 202 (that is with a cis alkene in the ring). As this is a cyclic enol ether, a boat-like transition state is expected and the formation of a single diastereoisomer of 203 confirms that this is true. Diagrams 204 and 205 should clarify the conformation of the molecule as it reacts, the mechanism, and the stereochemistry of the product. The product was converted into kainic acid 206 in a few steps. 

Weigang95 has measured the solvent shifts for all the electronic transitions of phenanthrene, naphthalene and azulene in a series of paraffin hydrocarbon solvents. The effect of branching and cyclization was studied by the inclusion of various structural isomers. Normal hydrocarbons give remarkable linear shifts, and these shifts fit well into the McRae theory87. The corresponding non-cyclic branched and cyclic hydrocarbons produce lesser shifts. These small shifts have been attributed to the change in the physical conformation of the molecule and the resultant opportunity for closer interactions with the chromophore. 

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