Crystal structure prediction conformational analysis

Gavezzotti A (1994) Are crystal structures predictable Acc Chem Res 27 309-314 AUinger Nl, Miller MA, Van Catledge FA, Hirsh JA (1%7) Conformational analysis.LVIl. The calculation of the conformational structures of hydrocarbons by the Westheimer-Hendrickson-Wibetg method. 1 Am Chem Soc 89 4345 357... 

The main structural features of compound 1 are the seven-membered ring and the orientation of the dimethylallyl group. We believe that it is not possible by calculation accurately to predict the exact conformation of the side chain the usefulness of a crystal structure is also limited concerning this flexible group. The seven-membered ring contains three planar atoms and has some similarity with cyclohexene we expect therefore the existence of two conform-ers that are related to the two twist forms of cyclohexene. A conformational analysis using MNDO [5] supports this assumption. For our model we have used the conformer with the lowest MNDO heat of formation, which is also in agreement with a published X-ray structure of a chloro derivative of TIBO [6]. 

Conformational analysis has been used to find and predict conformations which maximize antibiotic activity, using x-ray crystal structures coupled with nmr and cd spectra. An eady approach utilized the Dale diamond lattice conformational model (480), which was extended to other diamond lattice models (472,481—483). Other studies have relied on nmr data (225,484—491). However, extensive correlations between conformation and biological activity have not been successful (486,492). 

---